Дисертації з теми "Antibiotic delivery"
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Nikam, Shantanu P. "LOCALIZED ANTIBIOTIC DELIVERY VIA VALINE BASED POLY(ESTER UREA)." University of Akron / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=akron1522931095020122.
Повний текст джерелаStauber, Zachary Jason. "Microneedle delivery for improved efficacy of antiretroviral and antibiotic drugs." Thesis, Massachusetts Institute of Technology, 2012. http://hdl.handle.net/1721.1/76127.
Повний текст джерелаCataloged from PDF version of thesis.
Includes bibliographical references (p. 51-53).
Two classes of drugs, antiretrovirals and antibiotics, could benefit greatly from delivery through microneedles. Microneedles (MN) offer an increase in efficacy for these drugs by providing delivery to the lymphatic system through the skin, thus avoiding first pass metabolism and allowing more focused delivery to specific viral or bacterial reservoirs. Furthermore, microneedles present other advantages in the form of the ability to be self-administered, tunable controlled release, and painless administration. Saquinavir and Ciprofloxacin, an antiretroviral and an antibiotic respectively, were chosen for their optimal properties, including bioavailability, half-life, and dosage. Saquinavir was encapsulated in the organic phase of biodegradable poly(lactide-co-glycolide) microparticles (MP) synthesized through a double emulsion. Similarly, Ciprofloxacin was encapsulated in the aqueous phase of the microparticles. In addition, Ciprofloxacin microcrystals were synthesized. The microparticles and microcrystals were then loaded into molded polymer microneedles in a poly-acrylic acid (PAA) matrix. Standard curves were created for the two drugs from known concentrations and used to show the drug loading in the microparticles and microneedles. The Saquinavir microparticles showed a maximum loading of 1.35% the mass of particles and the Ciprofloxacin microparticles showed a maximum loading of 0.197%. The Saquinavir microparticle microneedles had a maximum loading of 11.95 [mu]g of Saquinavir per 1 cm² array and the Ciprofloxacin microparticle microneedles had a maximum loading of .41 [mu]g of Ciprofloxacin per 1 cm² array. The Ciprofloxacin microcrystal microneedlees had a maximum loading of 165 [mu]g per 1 cm² array. Analysis based on insulin delivery through microneedles showed these loadings to be too low to create the sufficient minimum drug concentration in plasma. However, there exist multiple strategies to increase the loading of the drugs in the microneedles. These results proved promising for the use of microneedles for the delivery of antiretroviral and antibiotic drugs.
by Zachary Jason Stauber.
S.B.
Escher, Geraldine. "Cellular delivery using peptoid carriers." Thesis, University of Edinburgh, 2013. http://hdl.handle.net/1842/12260.
Повний текст джерелаDallal, Bashi Yahya Haseeb Yahya. "Development of liposomes as pharmaceutical carriers for antibiotic and gene delivery." Thesis, Queen's University Belfast, 2017. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.725746.
Повний текст джерелаMandavyapuram, Hima Bindu. "ANTIBIOTIC DELIVERY SYSTEM FOR SURGICAL SITE INFECTION PREVENTION IN SPINAL IMPLANT SURGERY." Case Western Reserve University School of Graduate Studies / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1275624787.
Повний текст джерелаThompson, Marc Aaron. "Keratin Microparticles for Drug and Cell Delivery." Diss., Virginia Tech, 2019. http://hdl.handle.net/10919/89345.
Повний текст джерелаDoctor of Philosophy
Keratins and keratin hydrogels may exhibit several properties that support their use for tissue engineering and regenerative medicine applications. Microparticle formulations of these hydrogels are an intriguing delivery vehicle for payloads for tissue engineering purposes. Here we examine the water-in-oil emulsion synthesis procedure to produce keratin microparticles that were analyzed based on drug loading characteristics. A suspension culture technique was developed to load bone marrow-derived mesenchymyal stromal cells (BM-MSCs). Finally, we tested these products to determine potentially beneficial outcomes for skeletal muscle tissue regeneration. Particles with a porous structure were obtained. The microstructure of these particles may lend them to applications in drug release or other payload delivery. Data showed an ability to load and unload specific drug payloads. Dense cell populations were loaded onto particles. Finally, studies show that both keratin and BM-MSCs support skeletal muscle development, with combinatorial treatments of cell-loaded particles conferring the greatest growth responses.
Wayakanon, Kornchanok. "Polymersome-mediated intracellular antibiotic delivery to treat Porphyromonas gingivalis-infected oral epithelial cells." Thesis, University of Sheffield, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.544178.
Повний текст джерелаUrbaniak, Michael Daniel. "Structural studies of binding to apo-neocarzinostatin." Thesis, University of Sussex, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.390819.
Повний текст джерелаWang, Yang. "Antibiotic-conjugated polyacrylate nanoparticles : new opportunities for development of anti-MRSA agents." [Tampa, Fla] : University of South Florida, 2006. http://purl.fcla.edu/usf/dc/et/SFE0001446.
Повний текст джерелаMeng, Hanyan. "DEVELOPMENT OF HUMAN HAIR KERATIN BIOMATERIALS FOR ANTIBIOTIC DELIVERY IN TREATMENT OF ACUTE BACTERIAL INFECTIONS." Miami University / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=miami1377184680.
Повний текст джерелаGERMANO, GLEICE CONCEICAO MENDONCA. "STUDY OF INTERACTIONS OF THE ANTIBIOTIC NORFLOXACIN AND ITS COPPER-PHENANTHROLINE COMPLEX WITH DRUG DELIVERY SYSTEMS." PONTIFÍCIA UNIVERSIDADE CATÓLICA DO RIO DE JANEIRO, 2018. http://www.maxwell.vrac.puc-rio.br/Busca_etds.php?strSecao=resultado&nrSeq=36049@1.
Повний текст джерелаCOORDENAÇÃO DE APERFEIÇOAMENTO DO PESSOAL DE ENSINO SUPERIOR
PROGRAMA DE EXCELENCIA ACADEMICA
Os sistemas de administração controlada de medicamentos (drug delivery) permitem a introdução de uma substância terapêutica no organismo e melhoram sua eficácia e segurança, controlando a taxa, o tempo e o local de liberação, o que diminui os efeitos colaterais.Nesse trabalho nos dedicamos a estudar dois possíveis sistemas de administração de fármacos: lipossomos associados a surfactantes, já bastante utilizados em farmacologia, e nanobastões de ouro, cujas propriedades únicas têm sido avaliadas em aplicações biomédicas. Os lipossomos têm-se destacado devido a sua estabilidade e baixa toxicidade, os surfactantes são tensoativos muito usados tanto em farmacologia como para estabilizar soluções coloidais de nanopartículas. Já os nanobastões de ouro têm perspectivas promissoras para utilização em entrega de fármacos devido a suas propriedades óticas e biocompatibilidade. Estudamos, por meio de espectrofotometria de fluorescência e de absorção UV-visível, a associação entre esses sistemas e uma classe de fármacos denominada fluorquinolonas, que são antibióticos de amplo espectro bacteriano. A norfloxacina (NFX), pertencente à segunda geração de fluorquinolonas, foi escolhida para esse trabalho por ser naturalmente fluorescente, o que facilita a análise das interações sem a introdução de sondas extrínsecas ao sistema. Segundo a literatura, a associação da NFX com íons metálicos produz modificações nas propriedades desse fármaco, como solubilidade e biodisponibilidade. Essas mudanças têm sido avaliadas como uma possível solução ao problema de resistência bacteriana a antibióticos. Esse trabalho foi dividido em duas partes: na primeira, estudamos a formação dos complexos ternários de NFX com cobre-fenantrolina em presença de lipossomos associados a surfactantes que modificam a distribuição de carga elétrica superficial desses sistemas; na segunda parte estudamos a associação de NFX a nanobastões de ouro estabilizados por diferentes surfactantes.
Drug delivery systems allow the introduction of a therapeutic substance into the body and improve its effectiveness and safety by controlling the rate, time and place of release, which reduces side effects. In this work, we study two possible drug delivery systems: liposomes associated with surfactants, which are already widely used in pharmacology, and gold nanorods, whose unique properties have been evaluated in biomedical applications. Liposomes have been remarkable because of their stability and low toxicity, and surfactants are widely used both in pharmacology and to stabilize colloidal solutions of nanoparticles. On the other hand, gold nanorods have promising perspectives for use in drug delivery due to their optical properties and biocompatibility.We study the association between these systems and a class of drugs called fluoroquinolones, which are broadspectrum bacterial antibiotics, using fluorescence spectrophotometry and UVvisible absorption. Norfloxacin (NFX), a second generation fluoroquinolone, was chosen because it is naturally fluorescent, which facilitates the analysis of interactions without the introduction of extrinsic probes into the system. According to the literature, the association of NFX with metal ions produces changes in the properties of this drug, such as solubility and bioavailability. These changes have been evaluated as a possible solution to the problem of bacterial resistance to antibiotics. This work was divided in two parts: first, we studied the formation of the ternary complexes of NFX with copper-phenanthroline in the presence of liposomes associated to surfactants that modify the distribution of surface electric charge of the systems; in the second part, we studied the association of NFX to gold nanorods stabilized by different surfactants.
Hall, Rachael Catherine. "KERATIN HYDROGELS FOR ANTIBIOTIC DELIVERY IN WOUND HEALING APPLICATIONS: DEVELOPMENT OF HPLC METHODS TO CHARACTERIZE RELEASE." Miami University / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=miami1407435625.
Повний текст джерелаGuo, Pengbo. "Bone targeting nanoparticle as a new platform of antibiotic agent delivery for the treatment of osteomyelitis." Diss., Temple University Libraries, 2019. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/577034.
Повний текст джерелаPh.D.
Osteomyelitis is a bone infection disease that is caused by microbes. One of the reason that a successful antimicrobial therapy has not been achieved in bone related infection is due to the physiological and structural limitations and multi-drug resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). Alendronate, a type of bisphosphonate, is a commonly used drug to treat osteoporosis that can strongly chelate with the calcium ions in bone mineral (hydroxyapatite), could be utilized as an active targeting moiety in a drug delivery system to bone tissues. Since nanomedicine can provide a robust drug delivery platform, with the properties of encapsulating molecules of different hydrophilicity, tunable drug release profile, and potential of differential targeting cells and tissues, we proposed a lipid-polymer nanoparticle system, Bone-Targeting Nanoparticle (BTN), with surface modified with covalently bonded alendronate. In this study, BTN encapsulates linezolid, which has dose-related adverse effect that prevent long duration usage. According to our current results, BTN demonstrates three distinguished traits that potentially improves the therapeutic effect of linezolid towards MRSA induced osteomyelitis: a) a hydrophobic polymeric core that can encapsulate a high amount of linezolid; b) alendronate as a targeting moiety that can guide BTN to bone tissue and accumulate near the site of infection; and c) a PEGylated lipid interface that can enhance the drug release profile and provide increased serum stability relative to standard delivery methods.
Temple University--Theses
Olof, Sandberg. "Construction and evaluation of plasma protein multilayers used for local drug delivery." Thesis, Linköping University, Department of Physics, Chemistry and Biology, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-56900.
Повний текст джерелаWith the studies performed in this theses the local drug delivery technique FibMat developed by the biotech company AddBIO, was shown to be applicable to other plasma proteins and drugs than the fibrinogen-bisphosphonate combination that is today being commercialized. Hence the potential for a broader field of application was demonstrated. The application targeted today is as a surface modification giving improved strength to bone around screws used in bone implants. The effect of changing protein and manufacturing conditions was studied with null ellipsometry. It was demonstrated that with changes in incubation temperature, pH and salinity the fibrinogen could be successfully exchanged for the plasma proteins human serum albumin and immunoglobulin G. With liquid scintillation counting it was shown that the developed protein multilayers were able to absorb and release the bone strengthening drug alendronic acid in levels comparable to that of the fibrinogen based ditto. Disk susceptibility tests with the bacteria S. Aureus showed a potential for antibacterial functionalization with gentamicin. The release was, in the case of the fibrinogen multilayer, detectable up to 48 hours. Similar test revealed an inability of silver nanoparticle incorporated protein multilayers to achieve inhibitory levels.
Hasan, Mohammad Raquibul. "Antibiotic Releasing Bone-Void Filler for the Treatment of Osteomyelitis: An Approach to Treat Infection and Aid Bone Regeneration." Diss., North Dakota State University, 2020. https://hdl.handle.net/10365/32077.
Повний текст джерелаAbeylath, Thotaha Wijayahewage Sampath Chrysantha. "Glyconanobiotics : novel carbohydrated nanoparticle polymers." [Tampa, Fla] : University of South Florida, 2007. http://purl.fcla.edu/usf/dc/et/SFE0001948.
Повний текст джерелаUysal, Berna. "Vancomycin Containing Plla Delivery System For Bone Tissue Biocompatibility And Treatment Of Implant Related Chronic Osteomyelitis." Master's thesis, METU, 2009. http://etd.lib.metu.edu.tr/upload/12611108/index.pdf.
Повний текст джерелаantibiotic must reach to effective dose in the bone. So that
for prevention and treatment of osteomyelitis controlled antibiotic release systems can be used. These systems have been developed to deliver antibiotics directly to infected tissue. As a carrier material
polymers are widely use. Polymer can be biodegradable or non biodegradable. The advantage of biodegradable polymers is
you do not need a second surgery for the removal of the carrier material from the body. In this study
vancomycin loaded PLLA/TCP composites were developed and characterized to treat implant related chronic osteomyelitis in experimental rat osteomyelitis model. Some of the composites were prepared by coating the vancomycin loaded composites with PLLA to observe the difference between the coated and uncoated composites. Also, some composites were developed free from the vancomycin to determine the biocompatibility of the composite for the bone tissue. The coating extended the release of the vancomycin up to 5 weeks and changed the surface morphology of the composites. According to the cell culture studies, vancomycin loaded PLLA/TCP composites promoted cell adhesion, cell proliferation and mineralization so
the composite was biocompatible with bone tissue. Radiological and microbiological evaluations showed that vancomycin loaded and coated vancomycin loaded PLLA/TCP composites inhibited MRSA proliferation and treat implant related chronic osteomyelitis.
Goldberg, Manijeh Nazari. "Best antibiotics for buccal delivery." Thesis, Massachusetts Institute of Technology, 2011. http://hdl.handle.net/1721.1/68466.
Повний текст джерелаCataloged from PDF version of thesis.
Includes bibliographical references (p. 64-66).
The purpose of the research was to identify the clinical and commercial benefits of switching from intravenous (IV) to buccal delivery of antibiotics. then, the research continued to select 3-5 antibiotics that best met the buccal delivery and market requirements. Methods: The research began with the hypothesis that some injectable antibiotics are good candidates for buccal delivery even with the limitations imposed by the buccal tissue. The thesis captures a two-year research period encompassing three critical fronts - the clinical viability of switching from IV to buccal delivery for antibiotics, the market's desire and readiness to switch, and the antibiotic brands available for commercialization. Then the research moved to drug identification and selection in order to assess the antibiotics that would best function in the buccal delivery model. Results: Intravenous (IV) antibiotics are usually reserved for severe infections that require faster treatment. Less aggressive bacterial growths are treated with oral antibiotics, which has fewer side effects and complications. In the past two decades, the understanding of drug transport across different tissues has increased resulting in improved patient adherence to the therapeutic regimen and pharmacologic response. The administration of drugs by transdermal or transmucosal routes are relatively painless, offers patients more choices, and reduces the need to establish intravenous access, which is a particular benefit for children and elderly. These alternative methods also provide clinical care providers with more choices to better manage their patient's course of treatment. In the past, clinicians administered sedatives, narcotics, and a variety of other medications by transdermal, sublingual, nasal, rectal, and even tracheal-mucosal routes. These delivery options have provided flexible practice settings and this paper intends to show that antibiotics could be the next set of drugs to be administered in variety of ways to provide patients and clinicians the best array of choices. Conclusion: A few years ago, the buccal delivery method was fairly unknown. However, advances in nano encapsulation, physiology, toxicity, and the availability of certain drugs make the timing ideal for introducing antibiotics that have undergone a highly selective process for delivering through the buccal tissue.
by Manijeh Nazari Goldberg.
S.M.
Hassan, Faizule. "Adenovirus Mediated Delivery of Decoy Hyper Binding Sites for Sequestration of an Oncogenic Transcription Factor HMGA as a Potential Novel Cancer Therapy and Antibacterial Activity of Local Mushrooms." Miami University / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=miami1511449587326648.
Повний текст джерелаBreier, Annette. "Grundlegende Untersuchungen zur Integration eines Wirkstofffreisetzungssystems in ein textiles Knochenimplantat am Beispiel des Antibiotikums Gentamicin." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-181922.
Повний текст джерелаTo reduce the risk of infection in the treatment of long bone defects, a novel embroidered bone implant is to be provided with an antibiotic drug delivery system. Prolonged and controlled drug release can be achieved by coating the thread material with antibiotics incorporated in a degradable polymer matrix. The chosen drug delivery system is composed of polylactide acid (PLA) or poly(lactide-co-glycolide) acid (PLGA) as matrix polymer and the antibiotic gentamicin. It is integrated into the textile structure by dip-coating providing the three different methods suspension, emulsion and layered. Each method bears its appropriate parameters to influence the releasing profile. The suspension-method and its parameters grain size and grain size distribution as well as mass fraction of the antibiotic and the coating thickness could be proved as the most feasible. In part II of this essay the chosen coating set-up gets optimized so that a drug release nearly along the whole required term can be achieved. Preliminary in vitro studies show a good cell tolerance besides a sufficient microbial efficacy
Oguejiofor, Wilson. "Investigating the delivery of antimicrobial proteins and aminoglycoside antibiotics to the airways." Thesis, Aston University, 2013. http://publications.aston.ac.uk/20895/.
Повний текст джерелаChindera, Kantaraja. "Cell uptake properties of Polyhexamethylene Biguanide (PHMB) and applications in intracellular delivery." Thesis, Royal Veterinary College (University of London), 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.618319.
Повний текст джерелаAtherton, J. C. "Local intra-gastric delivery of antibiotics in the treatment of Helicobacter pylori infection." Thesis, University of Cambridge, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.596207.
Повний текст джерелаTurnbull, Bruce Robert Rowe. "Evaluation of hospital and patient risk factors that influence the effective delivery of surgical prophylactic antibiotics." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape4/PQDD_0016/MQ52957.pdf.
Повний текст джерелаPilcer, Gabrielle. "New highly effective dry powder tobramycin formulations for inhalation in the treatment of cystic fibrosis." Doctoral thesis, Universite Libre de Bruxelles, 2008. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210447.
Повний текст джерелаIn order to deliver a high dose range of medication for highly-dosed drugs such as antibiotics, “carrier-free” DPI formulations of tobramycin were developed with the aim of minimizing the use of excipients. Briefly, dry powders were prepared by spray drying various suspensions of tobramycin in isopropanol.
First, as particle size is a key parameter in defining drug deposition in the lungs, the new Spraytec® laser diffraction method specifically modified for measuring the PSD of aerosolized drug was evaluated. The dispersion properties of various dry powder formulations were investigated using different laser diffraction and impaction apparatuses at different flow rates and using different inhalator devices. Different correlations between geometric and aerodynamic size data were demonstrated in this study. As a potential application, for the flow rate, the different inhalation devices and the drug formulations examined, the tobramycin fine particle fraction could be predicted from measurements obtained from the Spraytec® using linear relationships. Correlations (R² > 0.9) between the MMAD and the percentage of particles with a diameter below 5 µm could be demonstrated between the results obtained from the laser diffraction technique and the impaction method. Consequently, the Spraytec® laser diffraction technique was proved to be an important tool for initial formulation and process screening during formulation development of DPIs.
In order to modify the surface properties of the raw tobramycin powder, different powder compositions were formulated with the aim of studying the influence of the concentration of tobramycin in drug suspensions used for spray-drying, the lipid film composition (cholesterol:Phospholipon ratio) and the coating level (in percentage) on the physicochemical and aerodynamic characteristics of the antibiotic.
The results indicated that the application of a lipid coating around the active particles allowed an improvement in particle dispersion from the inhalator, decreasing raw powder agglomeration and thus enhancing drug deposition deep in the lungs. Moreover, these results seemed to be influenced by the amount and composition of the lipids in the formulations. The evaluation of the influence of the coating level showed that the deposition of only 5% w/w lipids (on a dry basis) was sufficient to improve particle dispersion properties during inhalation. The FPF, which is around 36% for the uncoated micronized tobramycin, was increased to up to about 68% for the most effective lipid-coated formulation. Of particular importance, these results revealed the need to add sufficient amounts of covering material in order to significantly modify the particle surface properties and reduce their tendency to agglomeration, while limiting the lipid level in the formulations in order to avoid any undesirable sticking and to allow the delivery of more of the active drug to the deep lung.
Another approach used to modify the surface properties of raw tobramycin was to coat the micronized particles with nanoparticles of the drug, produced by high pressure homogenization. The evaluation of the influence of the level of nanoparticle coating of the micronized particles showed that the presence of nanoparticles in the formulations improved the particle dispersion properties during inhalation. One microparticle was completely covered with a single layer or several layers of nanoparticles, in function of the percentage of nanoparticles in the mixture. Coating the fine drug particles with particles in the nanometer range was believed to reduce Van Der Waals forces and powder agglomeration. These various layers of nanoparticles also allowed a decrease in the cohesion of the powder by improving the slip between the particles.
On the other hand, suspensions containing solely nanoparticles were spray dried with various concentrations of surfactant in order to produce easily dispersible and reproducible micron-size agglomerates of nanoparticles during inhalation. The evaluation of the influence of the concentration of surfactant showed that deposition of only 2% w/w (on a dry basis) of Na glycocholate is sufficient to improve particle dispersion properties during inhalation. Consequently, the use of nanoparticles in dry powder formulations increased the FPF from 36% for the uncoated micronized tobramycin to about 61% for this latter formulation.
To modify the balance between the different forces of interactions without the need for any excipient, the influence of formulation components on the aerosolization characteristics of spray-dried tobramycin through the use of various proportions of water in the solvent used to prepare initial suspensions was investigated. These results showed that it is possible to modify the surface properties of the particles by coating the particles of drug with a homogeneously distributed film of the active compound dissolved in a solvent system containing a mixture of different solvents such as isopropanol and water. During nebulization of the suspension, droplets are composed of one or more particles in solid state surrounded with solvent containing the dissolved drug. It is hypothesized that during the drying step, dissolved tobramycin forms a coating of the amorphous drug around particles in suspension. The coating of drug particles can thus be used as an alternative approach that permits the modification of the surface properties of the particles, increasing the flowability, the desagglomeration tendency and the fine particle fraction deposited in the deep lung. So, the evaluation of the influence of the water content of the suspensions and the effect of the inlet temperature during spray-drying showed that the addition of 2% water v/v is sufficient to improve particle dispersion during inhalation. Of particular interest, as tobramycin is a very hygroscopic drug, the addition of water turned out to be a critical step. It was thus important to add a small amount of water to the solvent system and to process the drying step at a high temperature to produce formulations containing solely the active drug and showing a FPF of up to 50%.
Moreover, stability studies demonstrated that these optimized formulations (lipid-coated formulation, nanoparticle formulation and amorphous drug-coated formulation) were stable over a long time period at various ICH temperature and relative humidity storage conditions (25°C/60% RH, 30°C/65% RH and 40°C/75% RH). The formulations were shown to keep their crystalline state, initial PSD, redispersion characteristics and deposition results for more than twelve months.
In order to confirm these encouraging results, two optimized formulations (one with a lipid coating and another with amorphous drug coating) were selected and compared to the only commercially available tobramycin formulation for inhalation, Tobi® (nebulizer solution), by performing a combined in vivo scintigraphic and pharmacokinetic evaluation of tobramycin DPIs in nine CF patients.
In comparison with Tobi®, it was estimated that lung deposition, expressed as a percentage of the nominal dose, was 7.0 and 4.5 times higher for the lipid-coated and amorphous tobramycin-coated formulations, respectively. Moreover, the pharmacokinetic data, adjusted to the same drug dose as that of the Tobi® deposited in the lungs, showed that the AUC values were found to be 1.6 times higher for Tobi® than for DPI formulations. So this evaluation confirmed the superiority of dry powder formulations in terms of drug deposition and reduced systemic exposure in comparison with the conventional comparator product, Tobi®.
Thus, these new and orginal tobramycin DPI formulations based on the use of very low excipient levels and presenting very high lung deposition properties, were shown to offer very good prospects for improving the delivery of drugs to the pulmonary tract and to the widest possible patient population.
Doctorat en Sciences biomédicales et pharmaceutiques
info:eu-repo/semantics/nonPublished
Dall, Graham Fraser. "Investigation, using an in-vitro alginate biofilm model, into locally delivered antibiotic combinations to treat staphylococcal prosthetic infection." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/32254.
Повний текст джерелаBirault, Albane. "Synthèse et caractérisation de silices hybrides fonctionnelles pour une délivrance autonome de molécules thérapeutiques." Thesis, Montpellier, Ecole nationale supérieure de chimie, 2018. http://www.theses.fr/2018ENCM0010.
Повний текст джерелаThe work developed in this thesis is devoted to the design of functional hybrid silica platforms for controlled delivery of therapeutics (e.g. oncologic drugs, antibiotics, etc.) to improve their performance and limit their side effect. The different types of silylated hybrid materials synthesized and described herein, including (1) pH-sensitive nanoparticles; (2) multi-functional periodic mesoporous organosilicas (PMO) mesostructured via PIC micelles; and (3) sophisticated core-shell and raspberry-type PMO hybrids; demonstrate hierarchical organization over multiple length scales, providing appealing features for drug delivery applications.The manuscript focusses, in particular, on the mechanisms controlling pore nanostructuring, using different type of structuring agents (e.g. CTAB, polyion complex (PIC) micelles, silica seeds or decane droplets) and on the subsequent structure-function relationship. The research project also demonstrated the potential of specific systems for future applications in biomedicine articulated
Tirelle, Pauline. "Role du microbiote intestinal dans la régulation de l'axe intestin-cerveau au cours du modèle murin d'anorexie " activity-based anorexia Gut microbiota alteration in a mouse model of Anorexia Nervosa Comparison of different modes of antibiotic delivery on gut microbiota depletion efficiency and body composition in mouse Gut microbiota depletion affects nutritional and bahavioral responses to activity-based anorexia model in a sex-dependent manner Invalidation of Toll-like receptor 4 in intestinal epithelial cells modifies the response to activity base anorexia model in a sex-dependent manner." Thesis, Normandie, 2020. http://www.theses.fr/2020NORMR056.
Повний текст джерелаAnorexia nervosa (AN) is an eating disorder (ED) with female predominance, mainly characterised by a decrease of food intake leading to a severe body weight loss. Furthermore, psychiatric comorbidities are frequently observed in AN patients such as depression and anxiety. During the last decade, the role of microbiota-gut-brain axis in ED and anxiety-like behavior has emerged. Several studies reported gut microbiota dysbiosis in anorectic patients. Nevertheless, the pathophysiology of AN remains poorly understood. The aim of the present PhD thesis was to better understand the contribution of the gut microbiota in the regulation of gut-brain axis in the mouse model of anorexia "activity-based anorexia" (ABA). The ABA model combines spontaneous physical activity with a free running wheel access and a progressive limited food access. In a first study, we characterised the gut microbiota of C57Bl/6 male mice submitted to ABA model. We observed in ABA mice an increase of Lactobacillus and clostridium cocleatum belonging to genus of Clostridium, as well as a decrease of Burkholderiales. Interestingly, correlations between bacteria taxa and food intake, body weight and body composition have been observed. Then, we aimed to evaluate the response to ABA model of mice with gut microbial depletion. We thus compared in a second study different dosing and administration of large spectrum antibiotic treatments, either by oral gavages (once or twice a day) or by addition in drinking water. Although these three strategies led to a strong decrease of faecal bacteria, once day oral gavage induced proliferation of Gammaproteobacteria. Thus, antibiotics administration by oral gavage twice a day or in drinking water appear as the most appropriate modes to achieve gut microbiota depletion. In a third study, we then evaluated the response to ABA model of both male and female C57Bl/6 mice with antibiotic-induced microbiota depletion. Firstly, we observed that antibiotic administration led to an increase of fat mass and a decrease of lean mass. During the ABA model, gut microbiota-depleted mice exhibited a lower decrease of body weight compared to untreated ABA mice. In males, we also observed altered anxiety-like behavior in ABA mice with depleted gut microbiota. We thus showed that gut microbiota-depleted mice exhibited an altered response to ABA model in a sex-dependent manner. Finally, in order to decipher the underlying mechanisms, we focused on toll-like receptor 4 (TLR4), an endogenous receptor of lipopolysaccharides. Previous studies suggested TLR4 implication in the regulation of feeding and anxiety-like behaviors. To determine the involvement of intestinal TLR4, we submitted mice with intestinal epithelial TLR4 knockout to the ABA model. Again, we observed a sex-dependent response: a delayed and limited body weight loss in males and an increase of anxiety-like behavior in females. In conclusion, studies performed during this PhD thesis highlight the alterations and the role of gut microbiota in the activity-based anorexia model that appear to be sex-dependent
Dzidic, Majda. "Microbiota development and mucosal IgA responses during childhood in health and allergic disease." Doctoral thesis, Universitat Politècnica de València, 2019. http://hdl.handle.net/10251/125479.
Повний текст джерела[CAT] Antecedents: S'ha proposat que els patrons de colonització microbiana alterats durant la infància podrien ser en part els responsables de l'augment de malalties al·lèrgiques als països desenvolupats. La microbiota intestinal difereix en composició i diversitat durant els primers mesos de vida en els nens que després van desenvolupar una malaltia al·lèrgica. No obstant això, poc es sap sobre la importància de les respostes immunes de la mucosa a la microbiota intestinal en el desenvolupament d'al·lèrgies infantils. A més, les investigacions amb relació a l'efecte protector de la microbiota de la llet materna en el risc de desenvolupar al·lèrgies no han sigut concloents. Encara que la cavitat bucal és el primer lloc de trobada entre la majoria dels gèneres externs i el sistema immunològic, encara no s'ha descobert la influència dels bacteris en el desenvolupament d'una al·lèrgia durant la infància. Objectius: L'objectiu general d'aquesta tesi va ser avaluar la composició microbiana i la diversitat de mostres orals, fecals i llet materns, juntament amb la seva interacció amb IgA, per estudiar el paper del desenvolupament microbià durant el període de la infància primerenca a la salut i la malaltia al·lèrgica. Subjectes: Les mares i xiquets inclosos en aquest estudi formen part d'un estudi aleatori doble-cec a Suècia, entre el 2001 i el 2003, on es van avaluar els possibles efectes preventius de la suplementació amb Lactobacillus ATCC 55730 fins als 2 i 7 anys. En aquesta tesi, s'utilitzaren mostres de bebès arreplegades longitudinalment, obtinguts a 1 i 12 mesos, 3, 6, 12, 24 mesos i 7 anys, respectivament. A més, s'analitzaren les mostres de llet materna, arreplegades a un mes postpart de les corresponents mares. Mètodes: S'han utilitzat tecnologies de seqüenciació de nova generació dirigides al ARNr 16S, en combinació amb la classificació de les cèl·lules activades, per abordar les respostes de la mucosa cap als bacteris intestinals i de la llet materna. A més, s'utilitzà la seqüenciació d'Illumina MiSeq del gen 16S per descriure la colonització microbiana oral, i es van obtenir mostres longitudinals de saliva de menuts que varen desenvolupar al·lèrgies i d'alguns que es van mantenir saludables. Els nivells de càrrega bacteriana en diferents nínxols microbians s'han obtingut mitjançant la metodologia de qPCR i els nivells totals d'IgA de les mostres fecals es determinaren mitjançant l'immunoassaig ELISA. Resultats i conclusions: La colonització de la cavitat bucal durant la primera infància és transitòria, augmenta la seva complexitat amb el temps, i diversos factors externs influeixen en gran mesura el procés de maduració de la microbiota oral, amb un impacte a curt i llarg termini. Els canvis primerencs en la composició microbiana oral pareixen influir en la maduració del sistema immunològic i el desenvolupament d'al·lèrgies a la infància, així com la presència d'espècies bacterianes específiques pot ser important per a aquest progrés. A més, les respostes d'IgA alterades cap a la microbiota intestinal durant la infància precedeixen a les manifestacions relatives a la malaltia asmàtica i al·lèrgiques durant els primers 7 anys de vida. Per altra banda, el consum de llet materna amb una microbiota de riquesa reduïda al primer mes de vida podria augmentar el risc de desenvolupar al·lèrgia durant la infància. Els resultats observats en aquest estudi haurien de confirmar-se en cohorts humanes més grans i la importància dels factors ambientals post natals que influeixen en el desenvolupament de la microbiota primerenca han de ser més estudiats. Les investigacions futures deuen anar més enllà de la caracterització de la composició de la comunitat bacteriana i investigar els mecanismes funcionals entre els microorganismes colonitzadors primerencs, la maduració del sistema immunològic i el desenvolupament de l'al·lèrgia i l'asma durant la in
[EN] Background: It has been proposed that altered microbial colonization patterns during infancy may be partly responsible for the increase of allergic diseases in developed countries. The gut microbiota differs in composition and diversity during the first months of life in children who later do or do not develop allergic disease. However, little is known about the significance of early mucosal immune responses to the gut microbiota in childhood allergy development, and the findings regarding the protective effect of breastmilk microbiota in the risk of allergy development have been inconclusive. Furthermore, even though the oral cavity is the first site of encounter between a majority of foreign antigens and the immune system, the influence of oral bacteria on allergy development during childhood has not yet been reported. Objectives: The general aim of this thesis was to assess the microbial composition and diversity of oral, fecal and breastmilk samples, together with its interaction with IgA, in order to study the role of microbial development during early childhood in health and allergic disease. Subjects: The infants and mothers included in this study were part of a larger randomized double-blind trial in Sweden, between 2001 and 2003, where potential allergy preventive effects of Lactobacillus reuteri ATCC 55730 were evaluated until 2 and 7 years of age. In this thesis, we used longitudinally collected stool and oral samples from infants, obtained at 1 and 12 months and 3, 6, 12, 24 months and 7 years of age, respectively. Furthermore, we analyzed breastmilk samples, collected at one month post partum, from the corresponding mothers. Methods: Next-generation sequencing technologies targeting the 16S rRNA gene, in combination with cell activated cell sorting, were used in order to address mucosal IgA responses towards gut and breastmilk bacteria. Furthermore, sequencing of the 16S rRNA gene was used in order to describe oral microbiota colonization, in longitudinally obtained saliva samples, from children developing allergy or staying healthy. Bacterial load levels in different microbial habitats were obtained by qPCR methodology and total IgA levels of stool samples were determined by ELISA immunoassays. Results and conclusion: Colonization of the oral cavity during early childhood is transitional, increasing in complexity with time, and several external factors appear to greatly influence oral microbiota maturation, having either a short or a long-term impact. Early changes in oral microbial composition seem to influence immune maturation and allergy development in childhood, and the presence of specific bacterial species may be important for this progress. Furthermore, altered IgA responses towards the gut microbiota during infancy preceded asthma and allergy manifestations during the first 7 years of life, and consumption of breastmilk with a reduced microbial richness in the first month of life may increase the risk for allergy development during childhood. Findings observed here need to be confirmed in larger cohorts and the importance of postnatal environmental factors for early microbiota development should be addressed further. Future research should go beyond characterization of bacterial community composition and investigate the functional mechanisms between early colonizing microorganisms, immune maturation and allergy and asthma development during childhood.
Dzidic, M. (2019). Microbiota development and mucosal IgA responses during childhood in health and allergic disease [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/125479
TESIS
Morais, Guilherme Mota Horta. "Dry powder formulations for antibiotic pulmonary delivery." Master's thesis, 2018. http://hdl.handle.net/10362/41209.
Повний текст джерелаHenriques, Margarida da Silveira. "Evaluation of scaffolds for local antibiotic delivery to the bone." Master's thesis, 2020. http://hdl.handle.net/10451/52156.
Повний текст джерелаO osso é um tecido conjuntivo heterogéneo que apresenta uma estrutura mineralizada e complexa que promove o suporte estrutural do corpo humano. Nas últimas décadas muitas tecnologias ortopédicas e biomateriais têm vindo a ser desenvolvidos na tentativa de dar resposta ao aumento das doenças ósseas nomeadamente, as infeções e defeitos ósseos resultantes de diferentes etiologias como trauma, osteoartrose, osteoporose, doenças oncológicas, etc. Os enxertos ósseos têm surgido como uma estratégia para resolver algumas destas situações. Neste contexto, os scaffolds ósseos tridimensionais têm sido desenvolvidos com o objetivo de fornecer uma estrutura semelhante à do osso assim como permitir a adesão, proliferação, diferenciação e migração celular. Paralelamente, diferentes scaffolds vêm sendo estudados como sistemas de libertação de antibióticos com o intuito de permitirem uma libertação controlada do fármaco de forma a tratar o defeito ósseo, bem como prevenir e tratar infeções. Assim, diferentes antibióticos (em associação ou não) são incorporados em diferentes tipos de scaffolds obtidos por diferentes métodos de produção (convencionais ou avançados). Ensaios in vitro e in vivo têm sido realizados para avaliar os scaffolds produzidos. Em relação aos ensaios in vitro, a duração e perfil de libertação do fármaco assim como a atividade antimicrobiana têm sido estudadas. A duração da libertação do fármaco é variada consoante os scaffolds estudados. A maioria dos scaffolds estudados apresenta um perfil de libertação caracterizado por uma libertação inicial rápida seguida de uma libertação controlada. Os scaffolds apresentaram atividade antimicrobiana tendo esta sido avaliada contra os microorganismos mais frequentemente associados às infeções óesseas como Staphylococcus aureus, Staphylococcus epidermidis e Escherichia coli. Além disso, ensaios de citocompatibilidade são realizados com a finalidade de confirmar a ausência de toxicidade aguda e crónica não apenas in vitro, mas também in vivo. De forma geral, os resultados destes ensaios não apresentaram efeitos de citotoxicidade, demonstrando adesão, proliferação e até mesmo diferenciação celular. Relativamente aos ensaios in vivo, os scaffolds estudados apresentam resultados semelhantes aos obtidos com outros scaffolds nos ensaios in vitro. É necessário desenvolver mais estudos in vitro e in vivo para obter uma harmonização da avaliação dos scaffolds. Quanto aos estudos in vivo, realizados em animais devem ser posteriormente validados por ensaios clínicos.
Bone is a heterogeneous connective tissue presenting a mineralized architecture and a composite structure that purveys a framework to the human body. In the last decades, many orthopaedic technologies and biomaterials have been developed due to increase in bone diseases such infections, osteoarthritis, osteoporosis, oncological diseases, etc. Bone grafting is becoming a strategy to solve those situations. In this context, three-dimensional bone scaffolds are being developed with the purpose of having not only a similar structure to the bone but also to allow the attachment, proliferation, differentiation, and migration of the cells. In parallel, different scaffolds are being studied as antibiotic delivery systems with the aim of allowing a sustained release of the drug to treat the bone defect as well as to prevent and treat infections. In this way, different antibiotics (in association or not) are being loaded into different types of scaffolds obtained by different production techniques (conventional or advanced). In vitro and in vivo assays are being performed in order to evaluate the properties of the produced scaffolds. Regarding to the in vitro assays, the duration of drug release and the release prolife is being assessed as well as the antimicrobial activity. The duration of the drug release is variable according to the studied scaffolds. Most of the scaffolds studied shown a release profile characterized by an initial burst release followed by a sustained release. The scaffolds shown antimicrobial activity being that studied against the most common bone infection pathogens such as Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli. Furthermore, cytocompatibility assays are being performed to confirm the absence of acute toxicity and chronic toxicity not only in vitro but also in vivo. In general, the results of these assays did not show cytotoxic effects, demonstrating adhesion, proliferation and even cell differentiation. Regarding in vivo assays, the scaffolds studied shown similar results to the obtained with other scaffolds in the in vitro assays. More standardized in vitro and in vivo studies are needed to obtain more information. Regarding to the in vivo studies, they should be confirmed by clinical investigations.
Lai, Tzu-Hsiang, and 賴子詳. "An antibiotic delivery platform using in vitro packed AP205 VLPs." Thesis, 2019. http://ndltd.ncl.edu.tw/handle/9ww673.
Повний текст джерела國立臺灣大學
生化科學研究所
107
Nowadays, small molecular drugs are used for chemotherapy to treat cancer diseases despite that these small molecules are non-targeting drugs. However, all efficacious drugs have adverse side effects. In order to avoid these unwanted hazards, scientists dedicate efforts to develop a carrier, which is capable of delivering drugs to target cancer cells precisely instead of anonymously. VLPs (Virus like particles) is a nanoscale self-assembled protein-based cage that is composed of only capsid from virus. The surface of capsid is tolerated with chemical modifications or genetic engineering to present the targeting peptides and epitopes. By far, the Qβ, MS2, and HBVc VLPs have been extensively studied in application of vaccine and drug delivery. In this study, the AP205 VLPs are used to encapsulate two small molecular drugs, doxorubicin (dox) and neomycin (neo), through the RNA hairpin-capsomere interactions. The encapsulated RNA hairpin is phosphorothioated by T4 PNK reaction, and then covalently coupled with dox or neo through amine-to-sulfhydryl crosslinker. The AP205 VLPs dox and AP205 VLPs neo are packed successfully in vitro. However, both the in vitro packed VLPs show low cytotoxicity towards cancer cells, which indicates that low coupling efficiency of dox/neo to the RNA hairpin, contributing to a low level of compound loading within the VLPs. The dox/neo and RNA hairpin coupling require further investigations in future works.
Hulbah, Maram. "Development of An Antibiotic Marker-Free Gene Delivery System in Streptococcus gordonii." 2013. http://hdl.handle.net/10222/21770.
Повний текст джерелаKrähenbühl, Amstalden Maria Cecilia. "Development of a bacterial responsive antibiotic release system." Doctoral thesis, 2018. https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-163386.
Повний текст джерелаEin weltweites Problem des Gesundheitswesens ist die Entstehung von antibiotikaresistenten Bakterienstämmen, besonders Methicillin-resistenter Staphylococcus aureus (MRSA). Eine wichtige Ursache für Resistenzentwicklungen ist die unüberlegte Verschreibung von Antibiotika; allerdings das breite Wirkspektrum der meisten Substanzen ist ein stets vernachlässigter Aspekt. Dies betrifft nicht nur die Pathogene selbst, sondern auch die bakterielle Mikroflora des Patienten, die opportunistische Pathogene darstellen und in machen Fallen ebenfalls verschiedene Erkrankungen hervorrufen können. Unser Ziel ist die Entwicklung eines bioresponsiven Freisetzungssystems für Antibiotika. Das System besteht aus einem Polymer zur Optimierung der Pharmakokinetik, einem Peptidlinker sowie dem eigentlichen Antibiotikum. Die bakterielle Protease Aureolysin wird von S. aureus exprimiert, sobald sich das Bakterium in seinem virulenten Zustand befindet. Das Enzym schneidet den Linker, wodurch das Antibiotikum zum Teil freigesetzt wird. Da es noch an Aminosäureartefakte gebunden ist, muss es im Anschluss durch eine Aminopeptidase, einer Gruppe von Exoproteasen des humanen Plasmas, abgespalten werden. Die erste Phase des Projektes war die Suche nach einer passenden Peptidsequenz, die als Linker geeignet ist. Diese soll nur durch die Zielprotease und nicht durch andere humane Proteasen geschnitten werden, um die Spezifizität des Systems zu gewährleisten. Es wurden drei Sequenzen ausgewählt und mittels Festphasen-Peptidsynthese hergestellt. Diese wurden mit Aureolysin sowie humanen Matrix-Metalloproteasen (MMP) inkubiert; die Produkte wurden chromatographisch (RP-HPLC) charakterisiert und die enzymatische Aktivität bestimmt. Die von Plasminogen abgeleitete Sequenz wurde von keiner der Matrix-Metalloproteasen geschnitten, wohl aber von Aureolysin. Eine ausführliche Analyse des Aureolysin-Verdaus zeigte, dass der Linker innerhalb weniger Stunden komplett geschnitten wird. In der zweiten Phase wurde die Peptidsequenz als Crosslinker in verschiedene Hydrogelmatrices inkorporiert. Die Strategie war der physikalische Einschluss des Antibiotikums in das Hydrogel und die anschließende Freisetzung durch Spaltung dieser Sequenzen und Lockerung des Hydrogelnetzes auf molekularer Ebene. Hierfür wurde ein kommerzielles Hydrogelkit mit Maleinsäureamid-modifizierter PVA Matrix verwendet, die mit Thiol-funktionalisierten Linkern konjugiert werden können. Drei verschiedene Fluorophore wurden als Modelle für die Diffusionsversuche verwendet. Nur das glomeruläre green fluorescent protein (GFP) besaß eine ausreichend niedrige Diffusionskonstante und wurde deshalb als Prototyp für die weiteren Schneidversuche verwendet. Die Ergebnisse zeigen, dass der Fluorophor bei niedrigen Matrixkonzentrationen schnell aus den Poren in das umgebende Medium diffundiert, während er bei höheren Konzentrationen nicht freigesetzt wird. Die physikalische Inkorporierung des Antibiotikums wurde aus diesen Gründen verworfen und nicht durchgeführt. Als zweiter Versuch wurde der Fluorophor kovalent an den Linker gekoppelt, welcher im Anschluß an die Matrix konjugiert wurde. Die Inkubation mit Aureolysin und die nachfolgende RP-HPLC-Analyse zeigte einen Peak bei der Retentionszeit entsprechend dem Fragmentprodukt, das durch Inkubation des freien Linkers entsteht. Die kovalente Bindung zwischen der antimikrobiellen Substanz und dem Linker ist eine vielversprechende Strategie für eine bio-responsive Freisetzung. In der dritten Phase des Projektes wurde die Zersetzung des resultierenden Fragments nach Aureolysin-Verdau und die anschließende vollständige Freisetzung des Antibiotikums durch humane Aminopeptidasen untersucht. Die Konzentration an Aminopeptidasen im humanen Plasma wurde bestimmt und die durch Aureolysin entstehende Peptidsequenz an Aminofluorescein mittels EDC/NHS-Reaktion gekoppelt. Die Inkubation des Konstruktes mit der niedrigsten Aminopeptidase-Konzentration, die im Plasma bestimmt werden konnte zeigte, dass der Fluorophor in zwei Stunden vollständig freigesetzt wurde. Die letzte Phase hat sich mit der PEGylierung des Linker-Antibiotikum-Komplexes beschäftigt. Das Tetracyclin-analoge Antibiotikum Chelocardin wurde als Prototyp ausgewählt und am Helmholtz-Institut für Pharmazeutische Forschung des Saarlandes synthetisiert. Die Konjugation des Linker-CHD-Konstruktes an das Polymer wurde mittels kupferfreier Click-Chemie durchgeführt. Der PEGylierte Linker wurde in einer ähnlichen Rate durch Aureolysin geschnitten wie der freie Linker, was beweist, dass das Polymer keinen Einfluss auf die enzymatische Aktivität hat. Allerdings wurde während der Optimierung der Beladung von CHD je Polymermolekül eine sehr niedrige Freisetzung des Antibiotikums beobachtet, was durch Aggregatbildung der Konstrukte erklärt werden kann. Das entwickelte System ist eine interessante Delivery-Strategie für Antibiotika, welche hierdurch nur durch virulente S. aureus-Erreger freigesetzt werden
Ferreira, Inês da Fonseca Santos 1985-1. "Novel particulate antibiotic-loaded platforms as sustained drug delivery systems for bone infection treatment." Doctoral thesis, 2015. http://hdl.handle.net/10451/18378.
Повний текст джерелаThe most common infecting microorganisms in bone infections are staphylococci, namely Staphylococcus aureus and Staphylococcus epidermidis. Conventionally, complicated bone infections caused by Gram-positive bacteria are treated with vancomycin. However, emergence of resistant staphylococci to vancomycin led to the increased use of daptomycin, which is bactericidal against resistant staphylococci. However, in severe bone infections, daptomycin efficacy is often limited, due to insufficient drug bioavailability at the infected site and biofilm tolerance; hence novel approaches are needed to enhance daptomycin antibiofilm effect. Over the last decades, polymeric nano-/microparticles have emerged as a worthy strategy to enhance the antibiofilm effect of clinically available antibiotics. In this context, daptomycin was encapsulated into polymeric microparticles composed by poly(methyl methacrylate (PMMA), PMMA-Eudragit RL 100 (EUD) and poly-caprolactone (PCL). Vancomycin-loaded microparticles were also prepared as controls. All particles were obtained by an optimised double emulsion-solvent evaporation method and subsequently freeze-died. The final particles presented a spherical morphology within the micrometre size range, high drug encapsulation and yield of preparation. Additionally, the effect of the microparticles on cell viability of ISO-compliant cells, fibroblasts, and osteoblasts was tested. Although some formulations induced a slight decrease in cell viability, none of them was considered cytotoxic. Bearing in mind the main objective of this work, daptomycin-loaded PMMA-EUD and PCL microparticles presented the highest in vitro drug release, with concentrations above the minimal inhibitory and bactericidal concentration of the tested strains. Nevertheless, the antibacterial activity of all formulations was assessed against planktonic and sessile clinically relevant staphylococci by isothermal microcalorimetry (IMC). Further characterization of microparticles-biofilm interaction, as well as assessment of their effect on biofilm size, structure and metabolic state, was performed by fluorescence in situ hybridization (FISH). Daptomycin-loaded PMMA-EUD and PCL microparticles proved to be the most effective against the tested strains with high antibiofilm activity. Finally, the microencapsulation of daptomycin into polymeric carriers proved to be an advantageous approach, thus making them potential candidates as sustained drug delivery systems for bone infections treatment. In addition, the innovative combination of IMC with FISH was essential in order to gain further insights on the antibiofilm effects of microparticulate systems, as well as on their interaction with sessile bacteria.
Fundação para a Ciência e a Tecnologia (FCT), projeto PEst-OE/SAU/UI4013/2011; Fundo Europeu de Desenvolvimento Regional (FEDER)
Yu-PuChu та 朱育普. "Sustained release of antibiotic from bioactive micro arc oxidized TiO2 using γ-PGA for drug delivery". Thesis, 2015. http://ndltd.ncl.edu.tw/handle/whw8y3.
Повний текст джерелаSpicer, Patrick. "Two Stage Repair of Composite Craniofacial Defects with Antibiotic Releasing Porous Poly(methyl methacrylate) Space Maintainers and Bone Regeneration." Thesis, 2013. http://hdl.handle.net/1911/72042.
Повний текст джерелаVilhena, Cláudia Sofia Jorge. "Daptomycin : a review of properties, clinical use, drug delivery and resistance." Master's thesis, 2015. http://hdl.handle.net/10451/26923.
Повний текст джерелаDaptomycin is a branched cyclic anionic lipopeptide antibiotic that was discovered in the early 1980's but only got the FDA approval in 2003. This novel pharmaceutical molecule has demonstrated great in vitro activity against a wide range of aerobic and anaerobic gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. Daptomycin has a unique mechanism of action, not completely understood, involving a calcium-dependent dissipation of membrane potential leading to the release of intracellular ions from the cell and bacteria death. This antibiotic has been already approved for the treatment of patients with complicated skin and skin structure infections, right-sided endocarditis and bacteraemia. Local delivery of daptomycin is an emerging area of study. Current in vitro studies show that daptomycin can be eluted from polymethylmethacrylate, calcium sulfate and chitosan films. Emerging cases of resistance to daptomycin have been reported, commonly occuring by spontaneous mutations, and has been associated with prolonged use, osteomyelitis, acute myeloid leukaemia and leucocyte adhesion deficiency syndrome. This review examines the most recent literature evidences on daptomycin molecular structure, mechanism of action, bacterial spectrum, clinical uses, local delivery, toxicity and resistance.
Fernandes, Carolina Santos. "Biodegradable poly(trimethylenecarbonate)versus non-biodegradable poly(methyl methacrylate) beads as antibiotic delivery devices in the treatment of diabetic foot osteomyelitis." Master's thesis, 2015. http://hdl.handle.net/1822/42041.
Повний текст джерелаOsteomyelitis is a frequent complication of diabetic foot ulcers and/or diabetic foot infection. It is defined as an infection of bone tissue and it is an aggravated condition in diabetic patient due to their poor blood flow and elevated blood glucose levels, which can increase biofilm formation. In general, osteomyelitis cannot be eradicated merely by intravenous administration of antibiotics. A successful treatment will include a combination of surgical procedures, usually surgical debridement of dead infected tissue and local antibiotic therapy. Non-degradable delivery devices are currently used for local antibiotic administration. The poly(methylmethacrylate) (PMMA) is widely used to develop gentamicin-loaded beads that are implanted on the local of infection. Even though these beads are routinely used to treat osteomyelitis, they present several disadvantages, including the requirement for a second surgery to remove the beads after treatment. Hence, the use of biodegradable devices for antibiotic delivery in osteomyelitis is a very attractive alternative. The poly(trimethylene carbonate) (PTMC) is an enzymatically biodegradable polymer that does not produce acidic degradation products. In the current thesis, the suitability of PTMC to function as an antibiotic delivery device for the local treatment of osteomyelitis was explored. Gentamicin-loaded PTMC beads were produced and their release kinetics was assessed. The inhibition of biofilm formation was also evaluated for these beads and compared with the commercially available PMMA Septopal® beads. Additionally, the glucose influence in biofilm growth was also studied, namely medium with and without 2.6 g/L concentration of glucose was used to grow the biofilm The results showed that the mass of biofilm (Enterobacter cloacae, Staphylococcus aureus) increased when glucose was present in the culture medium, which may explain the difficulties that are observed in the treatment of diabetic foot osteomyelitis. The antibiotic release profile and inhibition of biofilm formation by the PTMC beads was found to be similar to the PMMA beads. Therefore, PTMC seems a promising biodegradable carrier to be used in the local treatment of osteomyelitis.
A osteomielite é uma complicação frequente em úlceras e/ou infeção do pé diabético. É definida como uma infecção do tecido ósseo, agravada em pacientes diabéticos devido ao baixo fluxo sanguíneo e elevado nível de glucose no sangue, o que pode contribuir para a formação de biofilme. Em geral, a osteomielite não pode ser erradicada meramente com administração intravenosa de antibióticos. Um tratamento bem-sucedido inclui uma combinação de procedimentos cirúrgicos, geralmente remoção cirúrgica do tecido infectado e morto, seguido de terapia antibiótica local. Dispositivos de administração nãobiodegradáveis são actualmente utilizados para a administração de antibióticos no local infectado. O poli (metacrilato de metilo) (PMMA) é amplamente utilizado para desenvolver sistemas de libertação controlada de antibióticos, e estes são implantados no local infetado. Embora as partículas de PMMA sejam utilizadas com frequência no tratamento da osteomielite, estas apresentam várias desvantagens, incluindo a exigência de uma segunda cirurgia para as remover, após o tratamento. A utilização de dispositivos biodegradáveis para a libertação de antibióticos no tratamento da osteomielite é uma alternativa muito atraente. O poli (carbonato de trimetileno) (PTMC) é um polímero enzimaticamente biodegradável que não produz produtos de degradação ácidos. No presente trabalho foi explorada a adequação de PTMC para funcionar como um dispositivo de administração de antibiótico para o tratamento local da osteomielite. Foram produzidas partículas de PTMC carregadas com gentamicina e a cinética de libertação do antibiótico foi avaliada. Adicionalmente, a inibição da formação de biofilme foi estudada e comparada com as partículas de PMMA Septopal® comercialmente disponíveis. Além disso, a influência da glucose no crescimento de biofilme também fez parte deste estudo e por conseguinte, desenvolveu-se um biofilme em meio sem e com glucose com uma concentração de 2.6 g/L Os resultados mostraram que a massa de biofilme (Enterobacter cloacae, Staphylococcus aureus) aumentou na presença de glucose no meio de cultura, o que pode explicar a dificuldade observada no tratamento da osteomielite do pé diabético. O perfil de libertação do antibiótico e a inibição da formação de biofilme para as partículas de PTMC foi semelhante ao encontrado para as partículas de PMMA. Nesse sentido, as partículas de PTMC parecem ser um transportador biodegradável promissor no tratamento local de osteomielite.
Gunasekaran, Christopher. "Effect of Denaturants, Organic Solvents and Salts on the Protein Stability, Drug Efficacy, Release and Delivery of the Enediyne Antitumor Antibiotic Chromoprotein, Neocarzinostatin." 2006. http://www.cetd.com.tw/ec/thesisdetail.aspx?etdun=U0005-0806200616441300.
Повний текст джерелаSudhahar, G. Christopher Paul, and 克利多弗. "Effect of Denaturants, Organic Solvents and Salts on the Protein Stability, Drug Efficacy, Release and Delivery of the Enediyne Antitumor Antibiotic Chromoprotein, Neocarzinostatin." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/80303002055343903267.
Повний текст джерела國立中興大學
化學系
94
Neocarzinostatin, the antitumor antibiotic chromoprotein from Streptomyces carzinostaicus, is a non-covalent complex of a highly stable all β-sheet apoprotein of 113 amino acids and a labile 9-membered enediyne chromophore. The apoprotein stabilize and transports its chromophore, also regulates its release in juxtaposition to the target DNA. The present study is intended to understand (i) the mechanism of the release of the chromophore from the chromoprotein complex; (ii) the structural stability of the carrier protein; and (iii) the mechanism of sodium chloride inhibition of DNA cleavage induced by neocarzinostatin. The first chapter of the thesis, the “Introduction”, is an elaborate account describing the system and the objectives along with reviewing the literatures dealing with the discovery, classification, structure, and mechanism of activity of enediyne antitumor antibiotics, with particular references to neocarzinostatin. The second chapter deals with the expression, purification, and preliminary biophysical characterizations of the recombinant aponeocarzinostatin. The third chapter describes the mechanism of the 2,2,2-trifluoroetanol-induced release of the chromophore. The studies involve circular dichroism, fluorescence, HPLC, and 1-dimensional nuclear magnetic resonance analyses of aponeocarzinostatin and the chromophore release. The results show that the release of chromophore occurs before the unfolding of aponeocarzinostatin becomes evident, suggesting that the release does not require a major conformational change in the protein. The fourth chapter describes the exploration of the natural driving force(s) underlying the chromophore release. The studies involved structural changes of aponeocarzinostatin and release kinetics of the chromophore in the presence of organic solvents (alcohols and acetonitrile) and salts. The results, in concert, suggest that the release of the chromophore, which precedes major conformational changes of aponeocarzinostatin induced by organic solvents, is caused by hydrophobic perturbation, rather than ionic. The fifth chapter describes experiments to assess the stability of aponeocarzinostatin against chemical denaturants and organic solvents, since the structural stability is an important requirement for being an efficient proteinaceous drug carrier. While aponeocarzinostatin retains almost its native structure in fairly high concentrations of organic solvents, it shows only partial unfolding at the maximum concentration of urea and guanidine hydrochloride. It also retains its structural integrity in the potent denaturant sodium n-dodecyl sulfate. The structural stability of aponeocarzinostatin against organic solvents and chemical denaturants is higher than that of cytochrome c, lysozyme, and several other proteins which are known to be stable. The comparison among proteins provides evidence to the unusually high stability of aponeocarzinostatin. The results highlight the appropriateness of aponeocarzinostatin to protect its labile chromophoric partner. The sixth chapter presents an attempt to understand the mechanism of salt inhibition of neocarzinostatin-mediated DNA strand scission, an unexplored aspect of neocarzinostatin activity. Earlier studies on neocarzinostatin elsewhere showed that sodium chloride inhibits the neocarzinostatin-mediated DNA strand scission. Our data from in vitro DNA cleavage experiments under different sodium chloride concentrations, performed in the presence of thiols (β-mercaptoethanol or glutathione), show that the salt-protein interaction is not be the major inhibitory factor. There is little effect of sodium chloride on the thermal stability of aponeocarzinostatin. Fluorescence analysis of release kinetics of the chromophore reveals little influence of salt on the rate of release. The DNA binding data suggest that the major inhibitory effect of salt on DNA cleavage is caused by preventing the binding of the chromophore with the target DNA.
Fragoso, Ana Sofia Fernandes. "Nanosized delivery systems for fluoroquinolones: a review and practical case formulation in the setting of multidrug-resistant bacteria." Master's thesis, 2019. http://hdl.handle.net/10316/88297.
Повний текст джерелаA resistência bacteriana apresenta-se nos dias de hoje como uma ameaça constante, com impacto não só ao nível da saúde da comunidade global como também na economia dos países. A ineficácia das quinolonas apresenta especial importância, uma vez que esta classe de antibióticos ocupa um lugar de destaque constituindo uma escolha comum de antibiotrapia.Com este trabalho pretende-se sistematizar os melhores métodos de produção, com vista à obtenção de características físico-químicas otimizadas para produção de formulações eficazes na erradicação de resistências. Estes novos sistemas de administração de fármacos minimizam os efeitos de bombas de efluxo, a formação de biofilmes, tendo ainda a capacidade de ultrapassar diversos problemas de farmacocinética. Para alcançar esse compromisso, foi realizada uma revisão sistemática da literatura para entender os principais usos das nanopartículas no cenário de resistência a antibióticos, bem como a integração e interpretação de uma série dados provenientes de experiências realizadas na Universidade de Coimbra, validando as informações descritas na literatura.Existem inúmeras classes de nanopartículas e optamos por abordar nanopartículas lipídicas, poliméricas e inorgânicas neste artigo devido à sua aplicação no contexto de resistências a antibióticos.Entre os processos de produção de nanopartículas lipídicas sólidas (SLN), a técnica de microemulsão apresentou os melhores tamanhos de partículas e ainda taxas de encapsulação mais eficientes. Quanto à produção de transportadores lipídicos nanoestruturados (NLC), o processo com o melhor tamanho de partícula foi a Homogeneização a Alta Pressão (HPH). Em relação às partículas poliméricas, as técnicas destacadas foram dessolvatação, coacervação e gelificação iónica. Os usos previstos de diferentes tipos de partículas nos respectivos contextos clínicos são discutidos em detalhes neste trabalho, considerando as diferenças nas propriedades farmacocinéticas e farmacodinâmicas.
The antibiotic resistance is a global threat to world’s public health, encompassing several challenges to human health as well as a huge economic burden. The unmet aimed efficiency of quinolones retains crucial interest and relevance since they are a common choice in antibiotherapy. This work aims to review the several nanoparticle production processes, in order to obtain delivery systems able to surpass bacteria’s widespread resistance. These new delivery systems minimize the efflux pump effects, the formation of biofilms and have the capacity of overcome pharmacokinetic issues. To achieve such commitment a critical analysis of literature was performed to understand the main usages of nanoparticles in antibiotic resistance setting, as well as a series of experiments performed in the University of Coimbra to validate whenever possible the information described by literature. Among numerous classes of nanoparticles, we have chosen to address lipid, polymeric and inorganic nanoparticles due to its appliance in the context of antibiotic resistances. Among production processes for Solid Lipid Nanoparticles (SLN), the microemulsion technique presented the best particle size and the most efficient encapsulation rate. As for the production of Nanostructured Lipid Carriers (NLC), the process with the best particle size was High Pressure Homogenization (HPH). Regarding polymeric particles, the highlighted techniques were desolvation, coacervation, and ionic gelation. The foreseen usages of different types of particles in the respective clinical settings are discussed in detail in this work, namely comprising the differences in pharmacokinetic and pharmacodynamic properties.
Alves, Ana Bernardina Cotrim Dias. "Locust bean gum-based microparticles for pulmonary delivery of antibiotics." Master's thesis, 2015. http://hdl.handle.net/10400.1/8238.
Повний текст джерелаA administração de fármacos por via pulmonar tem sido abordada com elevado interesse, conduzindo-se ao crescimento do desenvolvimento de sistemas de libertação específicos para esta via. A sua reduzida atividade enzimática, a prevenção do metabolismo hepático, a superfície elevada, o fino e permeável epitélio alveolar e a vasta rede vascular, tornam-na elegível para a administração sistémica. Mas também, por permitir a elevada deposição de fármaco em elevada concentração numa zona específica do pulmão, permitindo assim, aumentar a sua ação terapêutica, reduzindo a dose total, efeitos adversos sistémicos e efeito de primeira passagem. É largamente utilizada para a veiculação de fármacos para o tratamento local de doenças respiratórias como a asma e fibrose cística, e atualmente investigada para a veiculação de antibióticos para o tratamento de doenças infeciosas, como a pneumonia ou a tuberculose. A tuberculose apresenta ainda uma elevada prevalência e incidência a nível mundial, em 2012, estimou-se o aparecimento de 8.6 milhões de novos casos e 1.3 milhões de casos de mortalidade. Sendo que uma das principais causas de morte é a baixa adesão a terapia oral atual, e consequentemente a falha terapêutica desta. A administração de sistemas que veiculem fármacos antituberculosos tem sido vista como uma abordagem terapêutica que potencialmente será eficaz e segura. Os sistemas micropartículados produzidos, por exemplo, por atomização, tem sido bastantes explorados, devido, a se poderem modular as suas características, de modo, a que exibam características aerodinâmicas adequadas (tamanho geométrico, densidade e forma) para alcançar a região alveolar. A goma de alfarroba (LBG) é um polissacarídeo neutro, que é extraído a partir das sementes de alfarroba, e tem sido largamente utilizado, em aplicações farmacêuticas, devido, a sua baixa citotoxicidade, propriedade bioadesivas e gelificantes. Este polímero pertence a classe dos galactomanamos, e é composto por unidades de mannose e galactose, num ratio aproximadamente de 4/1. A sua estrutura molecular consiste numa ligação linear de unidades (1-4)--mannose com uma unidade de (1-6)-α-galactose. A obtenção de micropartículas com esta estrutura, e com capacidade de atingirem a região alveolar, permite proporcionar o direcionamento destes sistemas para os macrófagos alveolares, onde reside o agente infecioso, Mycobacterium tuberculosis, e permitirem que haja a libertação intracelular dos fármacos veiculados. Este direcionamento deve-se ao facto de os macrófagos alveolares infetados expressarem o receptor da mannose, que ao reconhecer estruturas com mannose, irá conduzir a sua fagocitose, de um modo, mais específico e rápido, comparativamente com sistemas que não tenham esta estrutura. Neste contexto, este trabalho propõe o desenvolvimento de sistemas microparticulados, utilizando a goma de alfarroba, para a produção de micropartículas através da técnica de atomização. Pretende-se que este polímero veicule dois fármacos antituberculosos de primeira linha, a isoniazida (INH) e a rifabutina (RFB). Os sistemas microparticulados obtidos serão caracterizados em termos de propriedades aerodinâmicas, de eficácia de encapsulação e capacidade de permitirem a libertação dos fármacos num ambiente alveolar e do fagolisossoma. A sua biocompatibilidade será analisada em duas linhas celulares representativas do epitélio alveolar (A549) e dos macrófagos alveolares (macrófagos diferenciados a partir de THP-1). A capacidade de as partículas com uma matriz de LBG em serem fagocitadas será avaliada na dose de 50 μg/cm2 em duas linhas celulares de macrófagos, macrófagos diferenciados a partir de THP-1 e em macrófagos alveolares provenientes de ratinho (NR8383). A capacidade destas micropartículas em ativarem macrófagos será também avaliada nos macrófagos diferenciados a partir de THP-1. A utilização da goma de alfarroba neste contexto nunca fora descrita anteriormente. Pelo que torna as quatro formulações desenvolvidas com diferentes ratios de fármacos, uma nova abordagem/proposta para a terapêutica de tuberculose, ou a sua potencial adaptação para outra doença infeciosa do trato inferior respiratório. Deste modo as formulações desenvolvidas foram: partículas sem fármaco: Unloaded LBG e partículas com fármaco (ratio polímero:fármaco), LBG.INH 10:1, LBG.RFB 10:0.2, 10:0.5, 10:1 e LBG.INH.RFB 10:1:0.5 e 10:1:1. Apesar de a goma de alfarroba formar dispersões viscosas, devido a não solubilizar por completo, foi necessário a adição de ácido clorídrico (HCl) 0.1 M, para que fosse possível a sua atomização. Permitindo-se assim obter com um rendimento satisfatório (entre 58 a 71%), micropartículas com tamanho adequado para a administração alveolar (entre 1.26 a 1.50 μm). Para além do tamanho adequado, apresentam também valores de densidade real (aproximadamente 1.45 g/cm3) e de diâmetro aerodinâmico (entre 1.27 a 1.90 μm), que indicam a sua capacidade de atingirem a zona alveolar. Apesar de a INH ser um fármaco hidrofílico e a RFB ser um fármaco hidrofóbico, foi possível a sua encapsulação na matriz hidrofílica da LBG, com valores elevados de eficácia de encapsulação (> 82%). Outra justificação para a adição de HCl na formulação, foi a necessidade, de na molécula de RFB, haver um processo de desprotonação, que permitisse a sua solubilização em meio aquoso. O perfil de libertação de INH e RFB foi analisado a partir da formulação LBG.INH.RFB 10:1:0.5, verificando-se a libertação de ambos os fármacos num perfil semelhante em meio com pH 7.4, representativo da região alveolar. O perfil de libertação de INH a partir da formulação de LBG.INH foi avaliado, em dois meios, o representativo da região alveolar, e um representativo do fagolissosoma dos macrófagos, pH 5, estrutura formada após a fagocitose da micropartícula, e onde se irá libertar o fármaco. Em ambos os meios se obteve um perfil de libertação rápido de INH. A biocompatibilidade dos fármacos, matéria-prima e sistemas micropartículados produzidos foi avaliada em duas linhas celulares, uma representativa do epitélio alveolar (A549) e outra representativa dos macrófagos alveolares (macrófagos diferenciados a partir de células THP-1). E é feita através da avaliação da atividade metabólica (MTT) e da libertação da enzima lactato desidrogenase (LDH). Os resultados obtidos nos dois testes foram concordantes entre si, e verificou-se que nas concentrações testadas o fármaco RFB é citotóxico, com um índice de concentração que inibe a proliferação/população celular em 50 % (IC50), nestas duas linhas celulares, idêntico aos ratios testados. Apenas formulações que contêm RFB, se observa uma redução da viabilidade celular para estas duas linhas celulares, abaixo, do limite aceitável para formulações farmacêuticas (70%). No polímero observa-se alguma citotoxicidade nas células A549, que não está presente nas Unloaded LBG. Diversas razões foram apresentadas para a explicação desta citotoxicidade da RFB, sendo que por comparação com as Unloaded LBG MPs, se justifica, que a presença de HCl necessário na formulação, em associação com a RFB faz com que exista um efeito sinérgico na redução da viabilidade celular. É proposto a redução do ratio de RFB para um inferior aos desenvolvidos, usar HCl 0.01M para a sua encapsulação, e testar um novo excipiente para a redução da viscosidade da LBG. A biocompatibilidade foi também avaliada, quando os sistemas micropartículados são apresentados em aerossol. As micropartículas selecionadas foram as seguintes: Unloaded LBG, LBG.INH 10:1, LBG.RFB 10:0.5 e LBG.INH.RFB 10:1:0.5 na dose 303 μg/cm2, correspondente à concentração mais elevada em que amostras foram testadas quando apresentadas em solução. As micropartículas foram insufladas sobre uma monocamada de macrófagos alveolares. Como em todas se apresentou uma elevada redução de citotoxicidade, selecionou-se as Unloaded LBG e LBG.INH.RFB 10:1:0.5 e testou-se na dose 50 μg/cm2, verificando-se um aumento da viabilidade celular, em ambas, mas maior nas partículas brancas. Reforçando também, que as doses testadas são elevadas, comparativamente com a dose fármaco/sistema administrada in vivo, onde se esperam melhores resultados de viabilidade celular. Através de citometria de fluxo, foi analisado a capacidade de os macrófagos fagocitarem micropartículas com a matriz de LBG nas linhas celulares referidas. Onde se verificou a existência de uma elevada percentagem de fagocitose nos macrófagos diferenciados a partir de THP-1 (99,5 %), e nas NR8383, uma preferência significativa por micropartículas de LBG (94,35 %) comparativamente com um polímero sem mannose na sua estrutura (53,16%). Após comprovada a capacidade dos macrófagos em fagocitarem micropartículas de LBG, foi avaliada a capacidade deste galactomanano em ativar macrófagos, diferenciados a partir de THP-1, e que se encontram no estado M0 de ativação, para o estado M1, com capacidade pro-inflamatória. Após a exposição destas células, á uma solução da matriz de LBG e de micropartículas de LBG.INH.RFB 10:1:0.5 na dose de 303 μg/cm2, verificou-se que, devido a sua estrutura, a LBG tem a capacidade de induzir a libertação de citocinas, factor de necrose tumoral α e interleucina 8, num nível idêntico ao lipopolissacarídeo, presente na parede bacteriana, e com num nível superior e estatisticamente significativo comparativamente com o nível basal. Estes resultados reforçam que as micropartículas obtidas a partir deste polímero, através de atomização, apresentam propriedades aerodinâmicas que permitem que atinjam a região alveolar, e sejam veículos de fármacos antituberculosos ou de um outro antibiótico. E devido a sua estrutura com mannose, permitem que haja um reconhecimento específico pelos macrófagos alveolares infetados, permitindo potenciar a sua fagocitose. Após este processo, estas micropartículas permitem a libertação dos fármacos em meio intracelular, e ainda, activarem os macrófagos, para um estado de ativação pro-inflamatório, que irá melhorar a resposta inflamatória, e consequentemente, um melhor controlo o agente infecioso.
Govender, Mershen. "Sequential delivery of antibiotics and probiotics employing a dual release mechanism." Thesis, 2015. http://hdl.handle.net/10539/17357.
Повний текст джерелаSon, Yoen Ju. "Dry powder antibiotics for inhaled anti-tuberculosis therapy." Thesis, 2010. http://hdl.handle.net/2152/ETD-UT-2010-12-2230.
Повний текст джерелаtext
Hong, Ding-Wei, and 洪鼎惟. "A study on the delivery system for antibiotics based on biodegradable, thermosensitive polymeric hydrogels." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/32917167341584445431.
Повний текст джерела國立清華大學
化學工程學系
102
The first part of this thesis focuses on mixed hydrogels. The mixed micelles were formed by mPEG-PLGA and mPEG-PCL, the mixed micelles aggregated to form hydrogels under certain temperature and concentration above 15 wt%. The mixed hydrogels can successfully encapsulate a typical hydrophilic drug (vancomycin). Experimental results show that the mixed hydrogels have the features of stable durg release properties and slow degradation. The second part of this thesis focuses on polyanhydride hydrogels. The thermosensitive micelles mPEG-PLCPPA and mPEG-PLCPHA copolymers compose of methoxy polyethylene glycol (mPEG), polylactic acid (PLA) and 1,3-bis(p-carboxyphenoxy)propane (CPP) or 1,6-bis (p-carboxyphenoxy) hexane (CPH) are fabricated for application as a novel hydrophilic drug carrier. The copolymer can self-assemble into micelles in phosphate buffered saline (PBS) by hydrophobic interaction. The sol-gel transition profiles were investigated by the tube flipped upside method and a rheometer. The drug release profiles were investigated in PBS at 37°C with different concentrations of mPEG- PLCPPA and mPEG-PLCPHA solution. The in vitro and in vivo biocompatibility were also evaluated. Bacterial inhibition zone assay was performed by encapsulation of vancomycin and cefazolin. The diameters of these micelles increased as the temperature increased. The micelles increased in viscosity because of the aggregation of hydrophobic segments while temperature increased from the room temperature to the body temperature. The micelle properties of hydrogel containing vancomycin or cefazolin compared with hydrogel without drug loading were not significant difference. During the in vitro degradation process, hydrogels demonstrated a lower degradation rate and a light decrease in pH value. The in vitro and in vivo cytotoxicity results showed that the copolymer micelles had excellent biocompatibility. In vitro drug release profiles revealed a stable vancomycin release for 10 days and a stable cefazolin release for 30 days. The hydrogel encapsulating vancomycin and cefazolin had good antibacterial effects. Based on the results, mPEG-PLCPPA and mPEG-PLCPHA are promising as injectable depot gels for drug delivery.
Rimmer, Stephen, V. Venuganti, S. MacNeil, P. Garg, I. Douglas, and S. Foster. "MRC/DBT Workshop UK-India Centre for Advanced Technologies-Minimising the indiscriminate use of Antibiotics (UKICAT–MA) 14th/15th March 2016, Hyderabad, India." 2016. http://hdl.handle.net/10454/8622.
Повний текст джерелаOn 14/15th March 2016 we held a MRC/DBT funded workshop on the theme of Materials to Combat Antibiotic Resistance. The workshop was part of a continuing series of events that are part of the work of UK-India Centre for Advanced Technologies-Minimising the indiscriminate use of Antibiotics (UKICAT–MA). The following is the collection of presentations and the results of discussions highlighting key themes for future work by this group. Combating antibiotic resistance is perhaps the biggest issue facing the global community in the 21st century and no other area, with the exception perhaps of nuclear conflict, has the capacity to significantly reduce living standards and mortality rates. Key objectives identified by WHO1 in this area among five key aspects, include: Objective 4-to optimize the use of antimicrobial agents Objective 5-new medicines, diagnostic tools, vaccines and other interventions Our aims in this series of workshops are to provide an Indo-UK forum for: discussions of our advances in providing technologies to address these objectives; facilitate the interface between UK and Indian clinicians, materials and biological scientists and to identify key areas for new projects. An important aspect of the work in a global context is that by combining the UK and Indian community and clinical experiences we cover most of the scenarios that the global population might expect to encounter
Martino, Victor Jean-Marc Robert. "Análise do uso de antimicrobianos locais no tratamento periodontal." Master's thesis, 2018. http://hdl.handle.net/10284/7345.
Повний текст джерелаPeriodontitis is an inflammatory disease that causes destruction of tooth supporting tissues, characterized by multifactorial etiology with pathogenic bacteria being the primary etiologic agents that live in the subgingival área. The basic treatment of chronic periodontitis is a mechanical debridement of periodontal pockets by scaling and root planing (SRP) in combination with efficient plaque control. Despite the proven efficacy, this therapeutic approach has, however, some limitations. So in recent years, have been studied adjuvants means to nonsurgical treatment, like administration of antimicrobial agentes, with the aim of improving the short and medium term, the healing periodontal. Various antimicrobial agents have been used effectively in the management of periodontal infection. Whether in the form of fibers, gel, chips, or microspheres, degradable or not, local administration of antimicrobial agents allows to maintain high and more constant concentrations at the target site for a desired period of time and reduces the adverse effects due to an systemic administration of antibiotics. The objective of this work of literature review was to evaluate the interest and potential of the use of local antimicrobial agents in periodontal disease and to compare their efficacy with systemic administration of antibiotic agents.