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1
Dickers, Kirsten. "Drug delivery devices from polyglycolide." Thesis, University of Cambridge, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.415267.
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Guan, Jingjiao. "Microfabricated particulate devices for drug delivery." Connect to resource, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1118247862.
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Thesis (Ph. D.)--Ohio State University, 2005.Title from first page of PDF file. Document formatted into pages; contains xxiii, 163 p.; also includes graphics. Includes bibliographical references (p. 118-123). Available online via OhioLINK's ETD Center
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Lei, Wang S. "Fabrication of drug delivery MEMS devices." Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/58271.
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Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2007."May 2007." Cataloged from PDF version of thesis.
Includes bibliographical references (p. 19).
There is considerable amount of interest in the immediate treatment of personnel involved in high risk situations on the battlefield. A novel approach to drug delivery on the battlefield based on MEMS technology is discussed. By combining three separately fabricated layers, a single implantable drug delivery device capable of delivering up to 100 mm3 of a vasopressin solution was developed. In vitro release of vasopressin was observed and the I-V response of the bubble generator was characterized. Results show that the voltage at the time of release is ~11V while the current is ~0.35A, giving a power output of 3.79W. The time to total release of the drug was less than 2 minutes.
by Wang Lei.
S.B.
4
Sinha, Piyush M. "Nanoengineered implantable devices for controlled drug delivery." The Ohio State University, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=osu1115138930.
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Sinha, Piyush Mohan. "Nanoengineered implantable devices for controlled drug delivery." Connect to this title online, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1115138930.
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Thesis (Ph. D.)--Ohio State University, 2005.Title from first page of PDF file. Document formatted into pages; contains xxii, 220 p.; also includes graphics (some col.). Includes bibliographical references (p. 202-220). Available online via OhioLINK's ETD Center.
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Jiang, Ninghao. "Ocular drug delivery using microneedles." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2006. http://hdl.handle.net/1853/19796.
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Thesis (Ph.D)--Chemical Engineering, Georgia Institute of Technology, 2007.Committee Chair: Prausnitz, Mark R.; Committee Member: Allen, Mark; Committee Member: Edelhauser, Henry; Committee Member: Geroski, Dayle; Committee Member: Nickerson, John; Committee Member: Sambanis, Athanassios.
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Ohbi, Daljit Singh. "Novel Elastomer Compositions for Medical Drug Delivery Devices." Thesis, University of Bolton, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.494268.
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Campbell, Christopher. "Poly(lactide-co-glycolide) devices for drug delivery." Thesis, University of Bath, 2008. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.500691.
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Ovarian cancer is one of the five most common causes of cancer death in women in the USA and UK. It is usually diagnosed when it is well established beyond the ovary in the peritoneum. Intravenous injection of cisplatin is a common palliative therapy for ovarian cancer patients. Intraperitoneal therapy has been shown to improve survival for patients. Poly(lactide-co-glycolide) (PLGA) is a biodegradable polyester which has been proven safe for medical implantation. PLGA microspheres or fibres have been considered in this work as depots for delivering intraperitoneal cisplatin directly to the tumour site. The aims of this work were (1) to develop microsphere depot formulations with improved drug release profiles compared to previous work; (2) Novel cisplatin containing solid and hollow fibres were to be developed and investigated as alternative structures for depot devices; (3) The drug release profiles were to be examined using mathematical models to allow rational comparison of the devices. It was found that cisplatin containing PLGA 65:35 solid and hollow fibres represent a novel, reproducible formulation for encapsulating higher amounts of cisplatin for an equivalent mass of excipient than other polymer formulations. The fibres developed in this study were able to maintain elevated concentrations of unbound cisplatin in the presence of a biological matrix for approximately 100 hours in vitro.
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Chu, Leonard Yi. "Dissolving microneedles for cutaneous drug and vaccine delivery." Diss., Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/37177.
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Currently, biopharmaceuticals including vaccines, proteins, and DNA are delivered almost exclusively through the parenteral route using hypodermic needles. However, injection by hypodermic needles generates pain and causes bleeding. Disposal of these needles also produces biohazardous sharp waste. An alternative delivery tool called microneedles may solve these issues.
Microneedles are micron-size needles that deliver drugs or biopharmaceuticals into skin by creating tiny channels in the skin. This thesis focuses on dissolving microneedles in which the needle tips dissolve and release the encapsulated drug or vaccine upon insertion. The project aimed to (i) design and optimize dissolving microneedles for efficient drug and vaccine delivery to the skin, (ii) maintain vaccine stability over long-term storage, and (iii) immunize animals using vaccine encapsulated microneedles. The results showed that influenza vaccine encapsulated in microneedles was more thermally stable than unprocessed vaccine solution over prolonged periods of storage time. In addition, mice immunized with microneedles containing influenza vaccine offered full protection against lethal influenza virus infection.
As a result, we envision the newly developed dissolving microneedle system can be a safe, patient compliant, easy to-use and self-administered method for rapid drug and vaccine delivery to the skin.
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Mualem-Burstein, Odelia Wheatley Margaret A. "Drug loading onto polymeric contrast agents for ultrasound drug delivery /." Philadelphia, Pa. : Drexel University, 2008. http://hdl.handle.net/1860/2811.
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Dolla, William Jacob Spenner Becker Bryan R. "Drug diffusion and structural design criteria for conventional and auxetic drug-eluting stents." Diss., UMK access, 2006.
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Thesis (Ph. D.)--School of Computing and Engineering and Dept. of Chemistry. University of Missouri--Kansas City, 2006."A dissertation in engineering and chemistry." Advisor: Bryan R. Becker. Typescript. Vita. Description based on contents viewed Jan. 26, 2007; title from "catalog record" of the print edition. Includes bibliographical references (leaves 127-130). Online version of the print edition.
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Patel, Samikumar R. "Suprachoroidal drug delivery to the eye using hollow microneedles." Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/47816.
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Delivering drugs to effectively treat diseases of the back of the eye can be a challenging task. Although pharmacological therapies exist, drug delivery devices and techniques are not very effective at targeting delivery of drugs to the diseased tissues. This work introduces a novel approach to effectively deliver drugs to target tissues such as the choroid and retina. The approach involves a device, a hollow microneedle, to administer the drug formulation into a unique location in the eye, the suprachoroidal space. This new route of administration and a device to accomplish the delivery may provide an effective way to treat diseases of the choroid and retina. The first part of the work determines the ex-vivo feasibility of delivering materials within the suprachoroidal space. The results show that fluids and particles can be delivered into the suprachoroidal space of rabbit, pig and human eyes using a hollow microneedle. It further examines the important parameters for injection of the particles within the suprachoroidal space. The data shows that injection pressure and microneedle length are important parameters for effective delivery of particles. The results lead to a theory on the mechanism by which the particles are delivered into the suprachoroidal space. The second part of the research aims to develop a reliable in vivo delivery device and study the surface area coverage of materials injected into the suprachoroidal space. A hollow glass microneedle device is developed and for the first time shown to be effective in delivering a fluid into the suprachoroidal space in vivo. Up to 100 µL of India ink could be delivered into rabbit eyes in vivo and the spread within the suprachoroidal space is characterized. The results show that a single microneedle injection can cover a significant percentage of the available suprachoroidal space. This is the first study to examine the spread of a material injected into the suprachoroidal space of a live animal. A hollow metal microneedle device is also developed and shown to be effective. The device was able to inject up to 150 µL of latex into suprachoroidal space of fresh human cadaver eyes. The spread of latex is characterized and the results also show that a significant portion of the suprachoroidal space can be covered. The final part of the study examines the clearance of materials injected into the suprachoroidal space of rabbit eyes in vivo. First a comparison of a suprachoroidal injection to a conventional intravitreal injection shows that a suprachoroidal injection is more targeted to the chorioretinal tissues. In addition hollow microneedles are shown to effectively target macromolecules and a therapeutic antibody to the chorioretinal tissues. A study of the clearance kinetics show half lives within the suprachoroidal space on the order of several hours. Nano- and microparticles were also injected into the suprachoroidal space and showed very effective targeting. These non-degradable particles are shown to be present in the suprachoroidal space for months. Basic visual safety assessments identified no adverse effects from the injection of these materials. This represents the first study to compare intraocular clearance kinetics between a suprachoroidal injection and an intravitreal injection. It is also the first study to examine the clearance of a variety of materials from within the suprachoroidal space. Overall this work shows that microneedles have the capability to deliver a variety of materials into the suprachoroidal space of rabbit, pig, and human eyes. The injection can be done in a minimally invasive way with the proper design of an injection device and can target the chorioretinal tissues more effectively than the currently used method. In addition particles have long residence times in the suprachoroidal space, so a particle based drug formulation could provide sustained delivery to the eye. This work represents the first comprehensive study on using the suprachoroidal space as a drug delivery route and also the first study to use hollow microneedles to deliver formulations into the eye in vivo.
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Colby, Aaron Henry. "Novel drug delivery systems: pH-responsive expansile nanoparticles & drug concentrating devices as tools for treating cancer." Thesis, Boston University, 2008. https://hdl.handle.net/2144/30651.
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Thesis (Ph.D.)--Boston UniversityNew strategies for treatment and methods of drug delivery are required for patients suffering from cancer-the second leading cause of death worldwide. Current chemotherapeutic treatments frequently suffer from poor water solubility, systemic toxicity, poor accumulation within the target tissues and an inability to eradicate all remaining tumor following resection procedures. Nanoparticles (NPs) are extensively investigated as a means to increase drug solubility, alter biodistribution, target specific sites within the body, and minimize drug side effects and, as such, numerous NP formulations are being investigated as drug delivery devices to assist in the treatment and management of cancer. We have developed a pH-responsive expansile nanoparticle (eNP) that can encapsulate the hydrophobic chemotherapeutic agent Paclitaxel (Pax) (a poorly water soluble, yet potent chemotherapeutic agent), and deliver it specifically to the intracellular compartment of tumor cells. Paclitaxel-loaded-eNPs (Pax-eNPs) localize specifically to regions of intraperitoneal (IP) tumors and, once taken up by tumor cells, undergo a conformational change upon exposure to the mildly acidic cellular endosome that results in eNP swelling and intratumoral drug release. In this work, we describe: 1) the clinical problem and cost (both humanitarian and fmancial) of local cancer recurrence following tumor resection; 2) the eNP delivery system and, specifically, we characterize the swelling of eNPs using microscopy and tunable resistive pulse sensing techniques; 3) the in vitro activity of Pax-eNPs in breast cancer cells; 4) the improved efficacy of Pax- eNPs compared to the standard clinical formulation of Pax (i.e., Pax dissolved in Cremophor/Ethanol) in a murine model of established peritoneal mesothelioma; and, 5) the ability of eNPs to act as intratumoral, intracellular drug concentrating devices. Further investigation of this NP-based drug delivery system will facilitate a greater understanding of the materials and devices used in the delivery of chemotherapeutic agents and may lead to the clinical translation and application of eNPs.
2019-05-01
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Cheng, Sean Jikang. "Numerical and experimental study of cyclone separators for aerosol drug delivery." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608073.
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James, Jeff. "The Interaction of Drug Particles with Materials Employed in Inhaled Delivery Devices." Thesis, University of Nottingham, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.517833.
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He, Hongyan. "Multifunctional medical devices based on PH-sensitive hydrogels for controlled drug delivery." The Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=osu1148318906.
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Wu, Jun, and 吴隽. "Drug delivery devices fabricated by microfluidic method and their applications in long-term antimicrobial therapy." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/198816.
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Controlled drug delivery devices provide numerous advantages such as reduced side effects, higher therapeutic efficiency and improved patient compliance. Biodegradable polymer has become the most important material for controlled drug delivery device because of the excellent biocompatibility and tunable physicochemical properties. Biodegradable polymeric drug delivery devices are usually processed into various types of micro-particles due to the ease of fabrication and administration. However, controlling the drug release kinetics of these microparticles is still a challenge. One important reason is that drug release kinetics is significantly influenced by the microstructure of drug delivery devices, which is difficult to control.
Microfluidic method is a group of technologies involved in the manipulation of fluids using channels in the scale of micrometers. Microfluidic method is particularly useful in controlling the structure of micro-droplets and generating homogeneous droplets. Therefore, microfluidics suggests great potential in controlling microstructures of drug delivery devices and drug release kinetics.
In this study, biodegradable polymer based controlled drug delivery devices were fabricated using microfluidic method. Various types of microstructures were developed such as microspheres, core-shell microspheres, hollow microspheres and hydrogel microspheres. The results showed that microstructures were well controlled by fluid flow rates and geometries of capillary microfluidic devices. Both hydrophobic and hydrophilic drugs could be delivered by choosing drug delivery devices with suitable microstructures.
Drug release kinetics of biodegradable polymeric microspheres has been studies a lot, yet complete understanding is still to be achieved. The diameter is an important factor which contributes to the drug release kinetics. However, the influence of diameter has not been systemically studied because monodisperse microspheres are difficult to obtain. Using microfluidic method, monodisperse PLGA microspheres with different diameters were fabricated to study the influence of diameter on drug release kinetics. It was found that diameter only influence the duration of the first phase (lag phase) in drug release process and smaller microspheres exhibited shorter lag phase. The relatively faster expansion of smaller microspheres was found to be responsible for the size effect by monitoring physicochemical changes during drug release.
Rifampicin, a broad-spectrum antibiotic, was encapsulated by PLGA microspheres and PLGA-alginate core-shell microspheres. The long-term antimicrobial effects of drug loaded microspheres were investigated by drug release test and antimicrobial test against Staphylococcus aureus. The results showed that drug delivery devices could provide antimicrobial effect for more than one month. These drug delivery devices show potential in applications of controlled drug delivery and long-term antimicrobial therapy.
In conclusion, drug delivery devices with different microstructures were fabricated using microfluidic method. The diameter of PLGA microspheres only influence the first phase of drug release profile (lag phase) and smaller microspheres exhibited shorter lag phase. The size effect is due to the relatively faster expansion rate of smaller microspheres. Rifampicin loaded PLGA microspheres and PLGA-alginate core-shell microspheres could provide sustained release of rifampicin for more than one month. The released rifampicin was able to inhibit the growth of Staphylococcus aureus. The controlled drug delivery devices presented showed great potential in long-term antimicrobial applications.published_or_final_version
Orthopaedics and Traumatology
Doctoral
Doctor of Philosophy
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Colby, Aaron Henry. "Novel drug delivery systems: pH-responsive expansile nanoparticles & drug concentrating devices as tools for treating cancer." Thesis, Boston University, 2014. https://hdl.handle.net/2144/12957.
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Thesis (Ph.D.)--Boston UniversityNew strategies for treatment and methods of drug delivery are required for patients suffering from cancer-the second leading cause of death worldwide. Current chemotherapeutic treatments frequently suffer from poor water solubility, systemic toxicity, poor accumulation within the target tissues and an inability to eradicate all remaining tumor following resection procedures. Nanoparticles (NPs) are extensively investigated as a means to increase drug solubility, alter biodistribution, target specific sites within the body, and minimize drug side effects and, as such, numerous NP formulations are being investigated as drug delivery devices to assist in the treatment and management of cancer. We have developed a pH-responsive expansile nanoparticle (eNP) that can encapsulate the hydrophobic chemotherapeutic agent Paclitaxel (Pax) (a poorly water soluble, yet potent chemotherapeutic agent), and deliver it specifically to the intracellular compartment of tumor cells. Paclitaxel-loaded-eNPs (Pax-eNPs) localize specifically to regions of intraperitoneal (IP) tumors and, once taken up by tumor cells, undergo a conformational change upon exposure to the mildly acidic cellular endosome that results in eNP swelling and intratumoral drug release. In this work, we describe: 1) the clinical problem and cost (both humanitarian and fmancial) of local cancer recurrence following tumor resection; 2) the eNP delivery system and, specifically, we characterize the swelling of eNPs using microscopy and tunable resistive pulse sensing techniques; 3) the in vitro activity of Pax-eNPs in breast cancer cells; 4) the improved efficacy of Pax- eNPs compared to the standard clinical formulation of Pax (i.e., Pax dissolved in Cremophor/Ethanol) in a murine model of established peritoneal mesothelioma; and, 5) the ability of eNPs to act as intratumoral, intracellular drug concentrating devices. Further investigation of this NP-based drug delivery system will facilitate a greater understanding of the materials and devices used in the delivery of chemotherapeutic agents and may lead to the clinical translation and application of eNPs.
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Gupta, Jyoti. "Microneedles for transdermal drug delivery in human subjects." Diss., Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/34770.
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Microneedles have been developed as a minimally invasive alternative to painful hypodermic needles to deliver modern biotherapeutics. Previously, several in-vitro and in-vivo animal studies have been conducted to show that microneedles increase skin permeability to a wide range of molecules that cannot cross the skin using conventional transdermal patches due to the skin's stratum corneum barrier. However, only a limited number of studies have been performed to study microneedle-based drug delivery in human subjects. Therefore, the objective of this study was to perform the first-in-humans microneedle studies to: a) characterize skin repair responses to solid microneedle insertion to determine the extent of increased skin permeability coupled with predictions of pharmacokinetics of drug delivered through premeabilized skin, b) determine the effect of hollow microneedle-based infusion parameters on flow conductivity of skin and pain and thereby identify barriers to fluid flow into the skin from hollow microneedles, c) assess the safety and efficacy of systemic therapeutic effects through measurement of pharmacokinetic parameters, pain and irritation for microneedle-based insulin delivery in type 1 diabetes subjects, and d) assess the safety and efficacy of local therapeutic effects though delivery of lidocaine to the skin. Results showed for the first time that solid microneedle-treated skin reseals rapidly (< 2 h) in the absence of occlusion whereas occluded skin reseals slowly (3-40 h) depending on microneedle geometry as determined by skin impedance measurements. Increased microneedle length, number, and cross-sectional area led to slower recovery kinetics in the presence of occlusion. This thesis also demonstrated that the flow conductivity of skin decreased as fluid was infused to the dermis through hollow microneedles due to the dense structure of the dermis. Microneedle retraction, low flow rates, and the addition of hyaluronidase helped increase flow conductivity. Microneedles were able to deliver 800 µl of saline to the dermis without causing significant pain. Further, microneedle-based insulin delivery in type 1 diabetes subjects revealed that microneedles provided faster pharmacokinetics and improved glycaemic control than conventional subcutaneous catheters. Lastly, microneedle-based lidocaine injection demonstrated that microneedles were less painful, as effective, and more preferred than hypodermic needles in anesthetizing clinically relevant areas.
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Sakhalkar, Harshad S. "Enhanced adhesion of biodegradable drug delivery vehicles to inflamed endothelium." Ohio : Ohio University, 2005. http://www.ohiolink.edu/etd/view.cgi?ohiou1129916752.
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Jung, Hyunchul. "Design, Fabrication and Characterization of Micro/Nano Electroporation Devices for Drug/Gene Delivery." The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1316541070.
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Rivera, Edgardo. "Affinity-Based Drug Delivery Devices and its Applications in the Modulation of Cellular Processes." Case Western Reserve University School of Graduate Studies / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=case1417792663.
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Pongsaanutin, Tarinee. "Fabrication and characterisation of calcium phosphate and liposome composites for potential drug delivery devices." Thesis, University of Oxford, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.249572.
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Tantipolphan, Ruedeeporn, and n/a. "Characterisation of protein-phospholipid interactions in implantable delivery systems." University of Otago. School of Pharmacy, 2007. http://adt.otago.ac.nz./public/adt-NZDU20071218.162425.
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Purpose: This thesis aimed to gain a better understanding of the effects of salts in modifying in vitro phase behaviour of lecithin and cholesterol solid implants and to obtain further information on in vitro protein release and stability.
Methods: Raman spectroscopy and partial least squares regression (PLSR) were used to investigate lecithin-cholesterol molecular interactions as a function of method of preparation. Lipid-salt interactions were studied by attenuated total reflectance Fourier transform infrared (ATR-FTIR) and Raman spectroscopy using principal component analysis (PCA). In vitro release of bovine serum albumin (BSA), a model protein, from lecithin and lecithin:cholesterol implants comprising 10 and 30% NaCl and CaCl₂ were performed. Size exclusion (SE) HPLC was used for quantitative and qualitative analysis of the released BSA. On hydration, changes in phase behaviour and implant morphology were studied by ATR spectroscopy and light microscopy. SE-HPLC, ATR and fluorescence spectroscopy were used to evaluate the structure of unreleased BSA. Protein adsorption on lipid films was studied by flow through ATR spectroscopy. Increased amide II peak area upon recirculation of BSA in salt solutions over hydrated lecithin and lecithin:cholesterol films cast on ZnSe prisms was used to quantify the deposition of BSA onto the lipid surfaces.
Results: Shifts in the Raman spectra suggested the lecithin headgroup may be involved in lecithin-cholesterol interactions. Greater R� and root mean square error of cross validation in the calibration curves of physical mixing and heating (120�C) methods reflected poor mixing in these preparations. The mean absolute residue and mean Mahalanobis distance values from the physical mixing and granulation methods indicated their spectral similarity and comparable level of lecithin-cholesterol interactions. Calcium exhibited stronger affinity for phospholipids than sodium and it induced headgroup hydration and reorganisation upon binding. PCA of ATR spectra was sensitive to cholesterol addition, calcium binding and method of preparation whilst PCA of Raman spectra only differentiated the presence of cholesterol. In vitro release of BSA from implants produced from wet granulation mixtures of lecithin and lecithin:cholesterol in the absence of salt showed retention of a high monomer content and the release profiles were similar to the literature. Cholesterol increased the swelling, induced phase transformation of lecithin and, subsequently, reduced the BSA release. Salts only slightly modified the BSA release from the lecithin implants. In contrast, for lecithin:cholesterol matrices salts greatly enhanced implant swelling, induced the formation of hydrated lecithin of heterogeneous size and inhibited the in vitro BSA release. Analyses of the protein showed increased aggregation of BSA with a high retention of native structure while retained within the swollen matrices. ATR spectra suggested that salts promoted protein adsorption onto hydrated lecithin surfaces and the effects depend on salt types (NaCl > CaCl₂) and concentration (0.1 M > 1.0 M) but not on lecithin:cholesterol surfaces.
Conclusion: PLSR and PCA can be used to investigate molecular interactions in the solid lipid matrices. In lecithin:cholesterol implants, salts modified the phase behaviour of lecithin which resulted in enhanced swelling, formation of hydrated lecithin of altered morphology and inhibition of in vitro BSA release.
25
Hilder, Tamsyn A. "Modelling nanostructures as nano-oscillators for applications in nanomedicine." Access electronically, 2008. http://www.library.uow.edu.au/adt-NWU/public/adt-NWU20080918.101103/index.html.
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Kam, Kin-wai, and 甘健威. "A systematic review of factors improving medication safety of oral medication via enteral feeding tubes in institutions." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/206916.
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Objective: Medication safety is always having great concern in healthcare. Giving oral medication through enteral feeding tubes is not uncommon and is a well-known area that prone to error happening. These errors may lead to inadequate treatment or adverse drug reaction resulting in unnecessary health care cost and wastage of public health resources. This systematic review aims to identify contributing factors on medication errors associated with administration of oral medication via enteral feeding tubes. With better understanding of the factors, improvement measures applicable to Hong Kong situations will be suggested.
Methods: Pubmed, Medline and Embase databases were searched up to February 2014 by using relevant keywords. Prospective studies with researcher analyzing the drug administration process to observe the occurrence of errors and evaluate the contributing factors and case reports on medical error with review of the place of errors and their potential root causes were considered to be potential relevant literature. Studies meeting the inclusion criteria were included and evaluated in this review. Studies were excluded based on the exclusion criteria.
Results and Discussion: An initial search of medical literature by searching engines identified 682 references. After appraisal for inclusion, 11 of them were included in this systematic review. For the findings, lack of knowledge, lack of the presence or the awareness of protocol, environmental factors, inter-disciplinary communication among healthcare professionals and the ability of inadvertent connection of both IV catheter and enteral feeding system had been identified to be key contributing factors to drug administration error. Taken account with the findings, measures to improve the existing local practice through educational reinforcement, establishing guideline and inter-disciplinary communication were suggested.
Conclusion: With consideration of the local situation in Hong Kong and the findings identified in this review, suggestions of improvement measures on different aspects have been made in this review. Involvement of government policy, institutional management and the collaboration of multi-disciplinary healthcare professional are essential for the success of these improvement measures. Besides, this review also revealed the lack of research on medication safety issue concerning feeding tube, further research in this area is required.published_or_final_version
Public Health
Master
Master of Public Health
27
Comolli, Noelle Kristine Lowman Anthony M. "Engineering a multifunctional scaffold for spinal cord repair /." Philadelphia, Pa. : Drexel University, 2007. http://hdl.handle.net/1860/2902.
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Dziubla, Thomas D. Lowman Anthony M. "Macroporous hydrogels as vascularizable soft tissue-implant interfaces : materials characterization, in vitro evaluation, computer simulations, and applications in implantable drug delivery devices /." Philadelphia : Drexel University, 2002. http://dspace.library.drexel.edu/handle/1721.1/36.
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Pastorino, David. "Calcium phosphate cements and foams: characterization of porosity and use as local drug delivery devices." Doctoral thesis, TDX (Tesis Doctorals en Xarxa), 2015. http://hdl.handle.net/10803/673603.
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The topic of this Philosophy Doctor Thesis tallies with the national project MAT2012 of the BBT group of UPC: "Pore4Bone: Biomimetic calcium phosphates: tailoring porosity from the nano- to the macroscale for osteoinduction, drug delivery and bone tissue engineering".
Bone is one of the most transplanted tissues globally, with around one million surgical procedures each year. Ageing of the population worldwide requires intense effort in designing efficient, clinically applicable multifunctional biomaterials for bone regeneration. The need for a higher volume of bone graft, and advanced solutions make synthetic bone grafts an attractive alternative to auto- or xenografts.
Synthetic calcium phosphate cements (CPCs) provide a high freedom of processing and conformation, and excellent biomimicry to natural bone. Biocompatible and osteoconductive per se , CPCs support in vivo remodeling of bone. The intrinsic micro- and nano- porosity of CPCs resulting from the spaces between the entangled crystals and aggregates once set is a key property when considering bone regeneration and local release of drugs. It provides free space for drug diffusion and fluid penetration, both of which are essential elements for drug release. Thus, a comprehensive characterization of the porosity, especially at the microscopic and nanoscopic scale is of paramount interest to identify these mechanisms, so it has been tackled in detail in this work.
Focusing on bone infections, the combination of antibiotics with osteogenic matrices like CPCs is explored in the PhD Thesis. Indeed, while bone infections and bone disorders are generally treated post-operatively by systemic administration of the indicated antibiotic, achieving a therapeutically efficient local delivery of the active principles is a key challenge, as it allows reducing secondary unwanted effects, drug interactions and diminishing the required dose due to the enhanced local bioavailability.
In particular, the relationship between antibiotic addition, porosity and drug release in calcium phosphate cements (CPCs) is highlighted and studied in this PhD Thesis. Finally the introduction of macropores in CPCs is investigated to manufacture antibiotic-releasing calcium phosphate foams (CPFs) for bone regeneration, which present clear clinical benefits over CPCs as multifunctional biomaterials. Indeed, the clinical performance of CPCs as local drug delivery devices is restricted by the relatively low penetration of corporal fluids through their micro or nanopores, preventing a complete release of the drug. The slow release of the entrapped antibiotic during the degradation of the CPC may generate a local concentration below the minimum inhibitory concentration, with the risk to foster the development of antibiotic-resistant bacteria. The addition of a network of interconnected macropores in CPCs represents a major advance by enhancing fluid circulation, and the consequent increase of the release rate of the antibiotic. Thus, in addition to the injectability and biomimicry of CPCs, the interconnected macroporosity of CPFs endows these materials with clear advantages not only in terms of tuning the release kinetics of active principles, but also when considering their excellent osteogenic properties.La presente Tesis doctoral se enmarca dentro del proyecto MAT2012 del grupo de investigación BBT de la UPC: "Pore4Bone: Biomimetic calcium phosphates: tailoring porosity from the nano- to the macroscale for osteoinduction, drug delivery and bone tissue engineering" financiado por el Gobierno de España. El hueso es uno de los tejidos más trasplantados mundialmente con hasta 1 millón de cirugías anuales. El envejecimiento de la población conlleva la necesidad de hacer grandes esfuerzos en el diseño de biomateriales multifuncionales, eficientes y clínicamente aplicables a la regeneración ósea. El aumento del número de injertos óseos necesarios y la necesidad de encontrar soluciones avanzadas hace que los biomateriales sintéticos sean una alternativa atractiva a los auto- o xeno- injertos actuales. Los cementos de fosfato de calcio (CPCs) son materiales muy versátiles en cuanto a los procesos de conformado, y presentan propiedades muy similares a las del hueso natural. Siendo materiales biocompatibles y osteoconductivos, los CPCs actúan de soporte al proceso de remodelación ósea in vivo . Además, los CPCs presentan una micro- y nano- porosidad intrínseca, que tiene su origen en los espacios entre los cristales que se forman tras el fraguado. Dicha porosidad es de gran relevancia en la regeneración ósea y la liberación local de fármacos, al proporcionar espacios disponibles para la difusión de los fármacos y la circulación de fluidos corporales, ambos procesos esenciales para la liberación del principio activo. En esta Tesis Doctoral se ha abordado la caracterización de la porosidad de los CPCs en profundidad, especialmente a escala micro- y nanoscópica, por ser de gran interés en la identificación de los mecanismos de regeneración ósea y liberación controlada de fármacos. En el caso de las infecciones óseas, en la presente Tesis Doctoral se explora la combinación de antibióticos con matrices bioactivas como los CPCs. Así, mientras las infecciones óseas se tratan habitualmente mediante la administración sistémica de antibióticos de forma post-operatoria, alcanzar una liberación local eficaz del principio activo es un reto clave, que permitiría reducir los efectos secundarios no deseados, minimizar las interacciones potenciales entre fármacos y disminuir la dosis necesaria, gracias a una mayor biodisponibilidad. En este Trabajo, se ha estudiado en profundidad la relación entre la incorporación de antibiótico, la porosidad y la liberación de fármaco en cementos de fosfato de calcio (CPCs). Además, se ha investigado la introducción de macroporosidad en los CPCs con el objetivo de fabricar espumas de fosfato de calcio (CPFs) capaces de liberar fármacos para regeneración ósea a nivel local, con claras ventajas frente a los CPCs como biomateriales multifuncionales. En efecto, la eficacia clínica de los CPCs como dispositivos de liberación local de fármacos está limitada por la relativamente baja penetración y circulación de los fluidos corporales en los mismos, impidiendo una liberación completa del fármaco. El riesgo de que el antibiótico atrapado en el material se libere lentamente durante la degradación del mismo, dando lugar a concentraciones locales de antibiótico inferiores a la concentración mínima inhibitoria, puede llevar a la generación de resistencia bacteriana al antibiótico. La adición de una red de macroporos interconectados en los CPFs representa un avance importante, puesto que aumenta la circulación de fluidos corporales en el biomaterial, incrementa el control sobre la cinética de liberación de fármacos y permite colonización celular. Así pues, los CPFs junto a la inyectabilidad y el biomimetismo de los CPCs, presentan a una macroporosidad interconectada que les confiere un elevado interés en vistas tanto a la regeneración ósea como a la liberación local de fármacos.
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Azimi, Mandana. "EVALUATION OF THE REGIONAL DRUG DEPOSITION OF NASAL DELIVERY DEVICES USING IN VITRO REALISTIC NASAL MODELS." VCU Scholars Compass, 2017. http://scholarscompass.vcu.edu/etd/4780.
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The overall objectives of this research project were i) to develop and evaluate methods of characterizing nasal spray products using realistic nasal airway models as more clinically relevant in vitro tools and ii) to develop and evaluate a novel high-efficiency antibiotic nanoparticle dry powder formulation and delivery device. Two physically realistic nasal airway models were used to assess the effects of patient-use experimental conditions, nasal airway geometry and formulation / device properties on the delivery efficiency of nasal spray products. There was a large variability in drug delivery to the middle passages ranging from 17 – 57 % and 47 – 77 % with respect to patient use conditions for the two nasal airway geometries. The patient use variables of nasal spray position, head angle and nasal inhalation timing with respect to spray actuation were found to be significant in determining nasal valve penetration and middle passage deposition of Nasonex®. The developed test methods were able to reproducibly generate similar nasal deposition profiles for nasal spray products with similar plume and droplet characteristics. Differences in spray plume geometry (smaller plume diameter resulted in higher middle passage drug delivery) were observed to have more influence on regional nasal drug deposition than changes to droplet size for mometasone furoate formulations in the realistic airway models.
Ciprofloxacin nanoparticles with a mean (SD) volume diameter of 120 (10) nm suitable for penetration through mucus and biofilm layers were prepared using sonocrystallization technique. These ciprofloxacin nanoparticles were then spray dried in a PVP K30 matrix to form nanocomposite particles with a mean (SD) volume diameter of 5.6 (0.1) µm. High efficiency targeted delivery of the nanocomposite nasal powder formulation was achieved using a modified low flow VCU DPI in combination with a novel breathing maneuver; delivering 73 % of the delivered dose to the middle passages. A modified version of the nasal airway model accommodating Transwell® inserts and a Calu-3 monolayer was developed to allow realistic deposition and evaluation of the nasal powder. The nanocomposite formulation was observed to demonstrate improved dissolution and transepithelial transport (flux = 725 ng/h/cm2) compared to unprocessed ciprofloxacin powder (flux = 321 ng/h/cm2).
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Martinez, Adam W. "Design and development of an elastin mimetic stent with therapeutic delivery potential." Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/45926.
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Stenting remains a common treatment option for atherosclerotic arteries. The main drawback of early stent platforms was restenosis, which has been combated by drug eluting stents; however, these stents have suffered from a higher incidence of late stage thrombosis. To address current stenting limitations, the major research focuses have been the development of the next generation of drug eluting stents and first generation bioabsorbable stents. The main objective of this dissertation was the design and development of a new class of bioabsorbable stent composed of elastin mimetic protein polymers. The first phase explored different stent design schemes and fabrication strategies. Successfully fabricated stents were then mechanically tested to ensure they possessed sufficient mechanical strength. Additionally, described herein is the potential to modulate the properties of the elastin mimetics through different crosslinking strategies. We have demonstrated that chemical crosslinking allows for the tailoring of the physical, mechanical, drug delivery, and endothelialization properties of these materials. The potential for drug delivery from this elastin mimetic stent was benchmarked as was the potential to endothelialize these stents. Furthermore, we developed the necessary delivery systems to allow for deployment in the rat aorta model.
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Sullivan, Sean Padraic. "Polymer microneedles for transdermal delivery of biopharmaceuticals." Diss., Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/33873.
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Biopharmaceuticals, including proteins, DNA and vaccines, are one of the fastest growing segments of the overall pharmaceutical market. While the hypodermic injection, the most common delivery method for these molecules, is effective, it also has limitations, including low patient compliance, need for medically trained personnel and biohazardous sharps after delivery. The overall goal of this thesis was to develop a new delivery system for biopharmaceuticals, based on dissolving polymer microneedles, which is effective and more patient compliant than the hypodermic needle.
Microneedles are microscopic needles that are large enough to insert into the skin to deliver drugs effectively, while being short enough to avoid the pain causing nerves deep in the skin. An additional benefit of polymer microneedles is that the needles completely dissolve in the skin, leaving behind no biohazardous sharps. There are significant material and fabrication issues that must be overcome in the development of this new device.
The first part of this thesis focused on the development of a new fabrication process, based on in situ photopolymerization, for the creation of polymer microneedles. These microneedles were shown to successfully insert into the skin, dissolving within a minute to deliver the encapsulated cargo, and retain full activity of encapsulated proteins.
Next, we applied the microneedle technology to the delivery of the influenza virus. We found that the reformulation process required to encapsulate the influenza virus in polymer microneedles did not affect the antigenicity or immunogenicity of the virus. In addition, we used coated metal microneedles to successfully immunize mice with the influenza virus, verifying the delivery capabilities of a microneedle system.
Finally, we used the dissolving polymer microneedles to successfully immunize mice with the influenza virus, resulting in full protection against lethal challenge after one immunization. This immune response was equivalent to the control intramuscular injection. In conclusion, we have developed dissolving polymer microneedles as an effective and patient compliant delivery system for biopharmaceuticals. This system could be especially applicable to mass immunization efforts or home use, since it can be self-administered and allows for easy disposal with no biohazardous sharps.
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Marquez, Soto Daniela Trinidad. "Plasmon-Mediated Photothermal Phenomena and Nanofabrication of Applicable Devices." Thesis, Université d'Ottawa / University of Ottawa, 2017. http://hdl.handle.net/10393/36002.
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This thesis studies the different ways in which the localized plasmon heating effect of gold nanostructures -activated by plasmon excitation via visible and/or NIR irradiation- can be used to obtain different outcomes following the nanofabrication of applicable devices. Both spatial and temporal control were obtained for each one of the systems developed upon the incorporation of plasmonic gold nanostructures. Spatial control was enabled in hybrid mesoporous drug delivery systems fabricated in this thesis through the localized surface plasmon heating effect that allowed the modification of the dynamics of diffusion of the cargo being delivered, thus giving rise to different rates of release that can be controlled by plasmon excitation. At the same time, the plasmon heating effect proved to be capable of controlling the start of the release by dismantling thermo-responsive gates previously incorporated, thus enabling also a wavelength-controlled feature that enhances the versatility of these systems. Spatial control was also conferred to the photo-patterning applications presented in this dissertation by influencing the degree of motility of gold nanorods (AuNRs) embedded in polymer matrices allowing them to self-assemble when the longitudinal plasmon of the incorporated nanostructures was excited; the patterns generated were quite robust and persisted for extended periods of time. Finally, the feature of spatial heating control was also conferred to catalysis. The Friedel-Crafts alkylation of anisole by benzyl chloride using spherical gold nanoparticles (AuNPs) supported on Nb2O5-based catalysts was performed at bulk temperatures below those necessary for the reaction to occur when using bare or modified Nb2O5; this was the result of the combination of bulk and localized plasmon heating produced -both- via plasmon excitation. This also demonstrates the possibility of using plasmon excitation as an alternative heat source in this type of reactions. By combining the plasmonic properties of metallic nanostructures with those granted by mesoporous materials, polymer matrices and Nb2O5-based materials it was possible to obtain light-activated systems endowed also with temporal control and wavelength control while preserving the original properties of each systems' components. Overall, the content of this thesis describes in detail the practical aspects of combining gold nanostructures with different materials and the rationale behind the development of systems with customized and controllable properties.
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Watts, Stewart Ian. "Development of thin film oral drug delivery devices for use in paediatric and palliative care patient populations." Thesis, University of Strathclyde, 2016. http://digitool.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=27503.
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Wang, Xiaoyang. "Design, Construction and Investigation of Synthetic Devices for Biological Systems." University of Cincinnati / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1314041031.
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Uguz, Ilke. "Organic Implantable Probes for in vivo Recordings of Electrophysciological Activity and Drug Delivery." Thesis, Lyon, 2016. http://www.theses.fr/2016LYSEM027/document.
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L’enregistrement et la stimulation in vivo de l’activité neuronale peuvent aussi bien servir pour la recherche médicale que pour les interfaces cerveau-machine. Les dispositifs à base d’électronique organique sont de prometteurs candidats pour ce faire, grâce à leur flexibilité et leur biocompatibilité. Le contrôle local de l’activité neuronale est la clé de nombreuses stratégies thérapeutiques visant à traiter les troubles neurologiques. Une solution idéale serait donc de fabriquer un dispositif capable de détecter l’activité neuronale et, en réponse, d’injecter des molécules endogènes. L’un des objectifs de cette thèse est de s’attaquer à cette problématique à l’aide d’un dispositif permettant à la fois de stimuler les cellules, et de mesurer l’activité neuronale, au même endroit, à l’échelle cellulaire. Nous présentons un dispositif organique capable de délivrer précisément des neurotransmetteurs in vitro et in vivo. En convertissant un signal électrique en la délivrance de neurotransmetteurs, le dispositif mime le fonctionnement d’une synapse. Le neurotransmetteur inhibiteur, l’acide γ- aminobutyrique (GABA), est relargué au niveau des électrodes d’enregistrement par l’activation d’une pompe ionique électronique. L’injection du GABA engendre l’arrêt de l’activité épileptique qui a été enregistré au niveau des électrodes. Des dispositifs multifonctionnels ouvrent de nombreuses possibilités, incluant des dispositifs thérapeutiques avec des boucles de retour, avec lesquels l’enregistrement local de signaux régule la délivrance d’agents thérapeutiques. De plus, nous avons également réalisé pendant cette thèse l’intégration de transistors organiques sur un film organique ultra fin, pour mesurer les signaux électrophysiologiques in vivo à la surface d’un cerveau de rat. Le dispositif, implanté de façon épidurale, montre des résultats surpassant certains dispositifs subduraux de taille similaire, permettant ainsi une approche moins invasive et efficace pour mesurer l’activité neuronaleRecordings and stimulation of in vivo neural activity are necessary for diagnostic purposes and for brain-machine interfaces. Organic electronic devices constitute a promising candidate due to their mechanical flexibility and biocompatibility. Local control of neuronal activity is central to many therapeutic strategies aiming to treat neurological disorders. Arguably, the best solution would make use of endogenous highly localized and specialized regulatory mechanisms of neuronal activity, and an ideal therapeutic technology should sense activity and deliver endogenous molecules simultaneously to achieve the most efficient feedback regulation. Thus, there is a need for novel devices to specifically interface nerve cells. Here, we demonstrate an organic electronic device capable of precisely delivering neurotransmit- ters in vitro and in vivo. In converting electronic addressing into delivery of neurotransmit- ters, the device mimics the nerve synapse. The inhibitory neurotransmitter, -aminobutyric acid (GABA), was actively delivered and stopped epileptiform activity, recorded simultaneously and colocally. These multifunctional devices create a range of opportunities, including implantable therapeutic devices with automated feedback, where locally recorded signals regulate local release of specific therapeutic agents. In addition, we demonstrate the engineering of an organic electrochemical transistor embedded in an ultrathin organic film designed to record electrophysiological signals on the surface of the brain. The device was applied in vivo and epidurally implanted could reach capabilities beyond similar sized electrodes allowing minimally invasive monitoring of brain activity
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Ali, Maryam Byrne Mark E. "Therapeutic contact lenses for comfort molecules." Auburn, Ala., 2007. http://hdl.handle.net/10415/1334.
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Gill, Harvinder Singh. "Coated microneedles and microdermabrasion for transdermal delivery." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2007. http://hdl.handle.net/1853/24711.
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Thesis (Ph.D.)--Bioengineering program, Georgia Institute of Technology, 2008.Committee Chair: Dr. Mark R. Prausnitz; Committee Co-Chair: Dr. Mark Feinberg; Committee Member: Dr. Mark Allen; Committee Member: Dr. Niren Murthy; Committee Member: Dr. Peter Hesketh; Committee Member: Dr. Robert Swerlick
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Chandrasekaran, Shankar. "Surface micromachined hollow metallic microneedles." Diss., Georgia Institute of Technology, 2003. http://hdl.handle.net/1853/15505.
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Choi, Seong-O. "An Electrically Active Microneedle Electroporation Array for Intracellular Delivery of Biomolecules." Diss., Georgia Institute of Technology, 2007. http://hdl.handle.net/1853/19710.
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The objective of this research is the development of an electrically active microneedle array that can deliver biomolecules such as DNA and drugs to epidermal cells by means of electroporation. Properly metallized microneedles could serve as microelectrodes essential for electroporation. Furthermore, the close needle-to-needle spacing of microneedle electrodes provides the advantage of utilizing reduced voltage, which is essential for safety as well as portable applications, while maintaining the large electric fields required for electroporation. Therefore, microneedle arrays can potentially be used as part of a minimally invasive, highly-localized electroporation system for cells in the epidermis layer of the skin.
This research consists of three parts: development of the 3-D microfabrication technology to create the microneedle array, fabrication and characterization of the microneedle array, and the electroporation studies performed with the microneedle array. A 3-D fabrication process was developed to produce a microneedle array using an inclined UV exposure technique combined with micromolding technology, potentially enabling low cost mass-manufacture. The developed technology is also capable of fabricating 3-D microstructures of various heights using a single mask.
The fabricated microneedle array was then tested to demonstrate its feasibility for through-skin electrical and mechanical functionality using a skin insertion test. It was found that the microneedles were able to penetrate skin without breakage. To study the electrical properties of the array, a finite element simulation was performed to examine the electric field distribution. From these simulation results, a predictive model was constructed to estimate the effective volume for electroporation. Finally, studies to determine hemoglobin release from bovine red blood cells (RBC) and the delivery of molecules such as calcein and bovine serum albumin (BSA) into human prostate cancer cells were used to verify the electrical functionality of this device.
This work established that this device can be used to lyse RBC and to deliver molecules, e.g. calcein, into cells, thus supporting our contention that this metallized microneedle array can be used to perform electroporation at reduced voltage. Further studies to show efficacy in skin should now be performed.
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Chakravarty, Prerona. "Photoacoustic drug delivery using carbon nanoparticles activated by femtosecond and nanosecond laser pulses." Diss., Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/33842.
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Cellular internalization of large therapeutic agents such as proteins or nucleic acids is a challenging task because of the presence of the plasma membrane. One strategy to facilitate intracellular drug uptake is to induce transient pores in the cell membrane through physical delivery strategies. Physical approaches are attractive as they offer more generic applicability compared with viral or biochemical counterparts. Pulsed laser light can induce the endothermic carbon-steam reaction in carbon-nanoparticle suspensions to produce explosive photoacoustic effects in the surrounding medium. In this study, for the first time, these photoacoustic forces were used to transiently permeabilize the cell membrane to deliver macromolecules into cells. Intracellular delivery using this method was demonstrated in multiple cell types for uptake of small molecules, proteins and DNA. At optimized conditions, uptake was seen in up to 50% of cells with nearly 100% viability and in 90% of cells with ≥90% viability, which compared favorably with other physical methods of drug delivery. Cellular bioeffects were shown to be a consequence of laser-carbon interaction and correlated with properties of the carbon and laser, such as carbon concentration and size, laser pulse duration, wavelength, intensity and exposure time. Similar results were observed using two different lasers, a femtosecond Ti: Sapphire laser and a nanosecond Nd: YAG laser. Uptake was also shown in murine skeletal muscles in vivo with up to 40% efficiency compared to non-irradiated controls. This synergistic use of nanotechnology with advanced laser technology could provide an alternative to viral and chemical-based drug and gene delivery.
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Alhamad, Bshayer R. "The Effect of Aerosol Devices and Administration Techniques on Drug Delivery in a Simulated Spontaneously Breathing Pediatric Model with a Tracheostomy." Digital Archive @ GSU, 2013. http://digitalarchive.gsu.edu/rt_theses/17.
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Background: Evidence on aerosol delivery via tracheostomy is lacking. The purpose of this study was to evaluate the effect of aerosol device and administration technique on drug delivery in a simulated spontaneously breathing pediatric model with tracheostomy.
Methods: Delivery efficiencies during spontaneous breathing with assisted and unassisted administration techniques were compared using the jet nebulizer (JN- MicroMist), vibrating mesh nebulizer (VMN- Aeroneb Solo) and pressurized metered-dose inhaler (pMDI- ProAirHFA). The direct administration of aerosols in spontaneously breathing patients (unassisted technique) was compared to administration of aerosol therapy via a manual resuscitation bag (assisted technique) attached to the aerosol delivery device and synchronized with inspiration. An in-vitro lung model consisted of an uncuffed tracheostomy tube (4.5 mmID) was attached to a collecting filter (Respirgard) which was connected to a dual-chamber test lung (TTL) and a ventilator (Hamilton). The breathing parameters of a 2 years-old child were set at an RR of 25 breaths/min, a Vt of 150 mL, a Ti of 0.8 sec and PIF of 20 L/min. Albuterol sulfate was administered with each nebulizer (2.5 mg/3 ml) and pMDI with spacer (4 puffs, 108 µg/puff). Each aerosol device was tested five times with both administration techniques (n=5). Drug collected on the filter was eluted with 0.1 N HCl and analyzed via spectrophotometry.
Results: The amount of aerosol deposited in the filter was quantified and expressed as inhaled mass and inhaled mass percent. The pMDI with spacer had the highest inhaled mass percent, while the VMN had the highest inhaled mass. The results of this study also found that JN had the least efficient aerosol device used in this study. The trend of higher deposition with unassisted versus assisted administration of aerosol was not significant (p>0.05).
Conclusions: Drug deposited distal to the tracheostomy tube with JN was lesser than either VMN or pMDI. Delivery efficiency was similar with unassisted and assisted aerosol administration technique in this in vitro pediatric model.
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Absher, Jason Matthew. "THE DEVELOPMENT OF MICROFLUIDIC DEVICES FOR THE PRODUCTION OF SAFE AND EFFECTIVE NON-VIRAL GENE DELIVERY VECTORS." UKnowledge, 2018. https://uknowledge.uky.edu/cme_etds/85.
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Including inherited genetic diseases, like lipoprotein lipase deficiency, and acquired diseases, such as cancer and HIV, gene therapy has the potential to treat or cure afflicted people by driving an affected cell to produce a therapeutic protein. Using primarily viral vectors, gene therapies are involved in a number of ongoing clinical trials and have already been approved by multiple international regulatory drug administrations for several diseases. However, viral vectors suffer from serious disadvantages including poor transduction of many cell types, immunogenicity, direct tissue toxicity and lack of targetability. Non-viral polymeric gene delivery vectors (polyplexes) provide an alternative solution but are limited by poor transfection efficiency and cytotoxicity. Microfluidic (MF) nano-precipitation is an emerging field in which researchers seek to tune the physicochemical properties of nanoparticles by controlling the flow regime during synthesis. Using this approach, several groups have demonstrated the successful production of enhanced polymeric gene delivery vectors. It has been shown that polyplexes created in the diffusive flow environment have a higher transfection efficiency and lower cytotoxicity. Other groups have demonstrated that charge-stabilizing polyplexes by sequentially adding polymers of alternating charges improves transfection efficiency and serum stability, also addressing major challenges to the clinical implementation of non-viral gene delivery vectors.
To advance non-viral gene delivery towards clinical relevance, we have developed a microfluidic platform (MS) that produces conventional polyplexes with increased transfection efficiency and decreased toxicity and then extended this platform for the production of ternary polyplexes. This work involves first designing microfluidic devices using computational fluid dynamics (CFD), fabricating the devices, and validating the devices using fluorescence flow characterization and absorbance measurements of the resulting products. With an integrated separation mechanism, excess polyethylenimine (PEI) is removed from the outer regions of the stream leaving purified polyplexes that can go on to be used directly in transfections or be charge stabilized by addition of polyanions such as polyglutamic acid (PGA) for the creation of ternary polyplexes. Following the design portion of the research, the device was used to produce binary particle characterization was carried out and particle sizes, polydispersity and zeta potential of both conventional and MS polyplexes was compared. MS-produced polyplexes exhibited up to a 75% reduction in particle size compared to BM-produced polyplexes, while exhibiting little difference in zeta potential and polydispersity. A variety of standard biological assays were carried out to test the effects of the vectors on a variety of cell lines – and in this case the MS polyplexes proved to be both less toxic and have higher transfection efficiency in most cell lines. HeLa cells demonstrated the highest increase in transgene expression with a 150-fold increase when comparing to conventional bulk mixed polyplexes at the optimum formulation. A similar set of experiments were carried out with ternary polyplexes produced by the separation device. In this case it was shown that there were statistically significant increases in transfection efficiency for the MS-produced ternary polyplexes compared to BM-produced poyplexes, with a 23-fold increase in transfection activity at the optimum PEI/DNA ratio in MDAMB-231 cells. These MS-produced ternary polyplexes exhibited higher cell viability in many instances, a result that may be explained but the reduction in both free polymer and ghost particles.
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Krishnan, Vinu. "Design and Synthesis of Nanoparticle “PAINT-BRUSH” Like Multi-Hydroxyl Capped Poly(Ethylene Glycol) Conjugates for Cancer Nanotherapy." Akron, OH : University of Akron, 2008. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=akron1217677351.
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Thesis (M.S.)--University of Akron, Dept. of Biomedical Engineering, 2008."August, 2008." Title from electronic thesis title page (viewed 12/9/2009) Advisor, Stephanie T. Lopina; Committee members, Amy Milsted, Daniel B. Sheffer, Daniel Ely; Department Chair, Daniel B. Sheffer; Dean of the College, George K. Haritos; Dean of the Graduate School, George R. Newkome. Includes bibliographical references.
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Thote, Amol Janardan Gupta Ram B. "Molecular bonding in product engineering." Auburn, Ala., 2005. http://hdl.handle.net/10415/1275.
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Mirza, Rizwan. "Customized Biomimetic Coatings for Hip and Spinal Implants to Reduce Implant-Related Infections and Promote Osseointegration." Case Western Reserve University School of Graduate Studies / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1291215710.
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Yerich, Andrew J. "Development of an Artificial Nose for the Study of Nanomaterials Deposition in Nasal Olfactory Region." Miami University / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=miami151187266403964.
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Razavi, Mashoof Arash. "High intensity focused ultrasound in ophthalmology : part one, transscleral drug delivery : part two, infrared thermography for scalable acoustic characterization, an application in the manufacture of a glaucoma treatment device." Phd thesis, Université Claude Bernard - Lyon I, 2014. http://tel.archives-ouvertes.fr/tel-00996286.
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Therapeutic ultrasound has become a topic of growing interest in ophthalmology. High intensity focused ultrasound (HIFU) for the treatment of glaucoma and ultrasound (US) drug delivery are the two main areas of research in this field. This work addresses these domains in two separate parts: transscleral ultrasound drug delivery (USDD), and infrared (IR) field characterization of an ophthalmic HIFU device for glaucoma treatment. The sclera is a promising pathway for ocular drug delivery, since transscleral administration can address both the anterior and posterior segments of the eye. Due to the low permeability however, efficient drug delivery is challenging. In this study, HIFU was investigated as a potential modality for an enhanced transscleral drug delivery (in vitro). Among US effects, cavitation was shown to be the major contributor to an enhanced USDD. A pulsed US protocol designed to maximum cavitation activity may therefore be a viable method for enhancing ocular drug delivery. In the second part, a new method of ultrasonic field characterization was developed for a multi-element HIFU device. This system is designed and produced for glaucoma treatment by Eyetechcare Company (Rillieux-la-Pape, France). The traditional hydrophone method for field characterization was prohibitively slow on an industrial scale. An alternative modality for rapid qualitative assessment of the intensity distribution based on infra-red (IR) thermography was developed specific to this high frequency (19-21 MHz) device with line-focus US radiators. The second part of the study was aimed to expand the application of a R&D technique for ultrasonic field characterization to an industrial scale
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Katsamba, Panayiota. "Biophysics of helices : devices, bacteria and viruses." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/283006.
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A prevalent morphology in the microscopic world of artificial microswimmers, bacteria and viruses is that of a helix. The intriguingly different physics at play at the small scale level make it necessary for bacteria to employ swimming strategies different from our everyday experience, such as the rotation of a helical filament. Bio-inspired microswimmers that mimic bacterial locomotion achieve propulsion at the microscale level using magnetically actuated, rotating helical filaments. A promising application of these artificial microswimmers is in non-invasive medicine, for drug delivery to tumours or microsurgery. Two crucial features need to be addressed in the design of microswimmers. First, the ability to selectively control large ensembles and second, the adaptivity to move through complex conduit geometries, such as the constrictions and curves of the tortuous tumour microvasculature. In this dissertation, a mechanics-based selective control mechanism for magnetic microswimmers is proposed, and a model and simulation of an elastic helix passing through a constricted microchannel are developed. Thereafter, a theoretical framework is developed for the propulsion by stiff elastic filaments in viscous fluids. In order to address this fluid-structure problem, a pertubative, asymptotic, elastohydrodynamic approach is used to characterise the deformation that arises from and in turn affects the motion. This framework is applied to the helical filaments of bacteria and magnetically actuated microswimmers. The dissertation then turns to the sub-bacterial scale of bacteriophage viruses, 'phages' for short, that infect bacteria by ejecting their genetic material and replicating inside their host. The valuable insight that phages can offer in our fight against pathogenic bacteria and the possibility of phage therapy as an alternative to antibiotics, are of paramount importance to tackle antibiotics resistance. In contrast to typical phages, flagellotropic phages first attach to bacterial flagella, and have the striking ability to reach the cell body for infection, despite their lack of independent motion. The last part of the dissertation develops the first theoretical model for the nut-and-bolt mechanism (proposed by Berg and Anderson in 1973). A nut being rotated will move along a bolt. Similarly, a phage wraps itself around a flagellum possessing helical grooves, and exploits the rotation of the flagellum in order to passively travel along and towards the cell body, according to this mechanism. The predictions from the model agree with experimental observations with respect to directionality, speed and the requirements for succesful translocation.
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Henry, Sʹebastien. "Microfabricated device for transdermal drug delivery." Thesis, Georgia Institute of Technology, 1997. http://hdl.handle.net/1853/20707.
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