Academic literature on the topic 'Biodistribution studies'
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Journal articles on the topic "Biodistribution studies"
Begent, R. H. J., and K. D. Bagshawe. "Biodistribution studies." Advanced Drug Delivery Reviews 22, no. 3 (December 1996): 325–29. http://dx.doi.org/10.1016/s0169-409x(96)00442-5.
Full textSilva Lima, Beatriz, and Mafalda Ascensão Videira. "Toxicology and Biodistribution: The Clinical Value of Animal Biodistribution Studies." Molecular Therapy - Methods & Clinical Development 8 (March 2018): 183–97. http://dx.doi.org/10.1016/j.omtm.2018.01.003.
Full textHuang, Ying, Mike Havert, Denise Gavin, Mercedes Serabian, Lee Lee Ong, Maritza C. McIntyre, Nicolas Ferry, et al. "Biodistribution studies: understanding international expectations." Molecular Therapy - Methods & Clinical Development 3 (2016): 16022. http://dx.doi.org/10.1038/mtm.2016.22.
Full textCastro-Balado, Ana, Cristina Mondelo-García, Miguel González-Barcia, Irene Zarra-Ferro, Francisco J. Otero-Espinar, Álvaro Ruibal-Morell, Pablo Aguiar, and Anxo Fernández-Ferreiro. "Ocular Biodistribution Studies Using Molecular Imaging." Pharmaceutics 11, no. 5 (May 16, 2019): 237. http://dx.doi.org/10.3390/pharmaceutics11050237.
Full textGonçalves, C., M. F. M. Ferreira, A. C. Santos, M. I. M. Prata, C. F. G. C. Geraldes, J. A. Martins, and F. M. Gama. "Studies on the biodistribution of dextrin nanoparticles." Nanotechnology 21, no. 29 (July 5, 2010): 295103. http://dx.doi.org/10.1088/0957-4484/21/29/295103.
Full textFerreira de Carvalho Patricio, Beatriz, Maria Helena Madruga Lima-Ribeiro, Maria Tereza dos Santos Correia, Ana Maria dos Anjos Carneiro-Leão, Marta de Souza Albernaz, Thiago Barboza, Sergio Augusto Lopes de Souza, and Ralph Santos-Oliveira. "Radiolabeling of Cramoll 1,4: Evaluation of the Biodistribution." International Journal of Peptides 2011 (June 30, 2011): 1–3. http://dx.doi.org/10.1155/2011/945397.
Full textSimões, Ana V. C., Sara M. A. Pinto, Mário J. F. Calvete, Célia M. F. Gomes, Nuno C. Ferreira, Miguel Castelo-Branco, Jordi Llop, Mariette M. Pereira, and Antero J. Abrunhosa. "Synthesis of a new 18F labeled porphyrin for potential application in positron emission tomography. In vivo imaging and cellular uptake." RSC Advances 5, no. 120 (2015): 99540–46. http://dx.doi.org/10.1039/c5ra16103g.
Full textAngra, Pawan K., Aladin Siddig, Henry Nettey, Nishil Desai, Carl Oettinger, and Martin J. D'Souza. "Pharmacokinetic and biodistribution studies of Amphotericin B microspheres." Journal of Microencapsulation 26, no. 7 (November 2009): 627–34. http://dx.doi.org/10.3109/02652040802587173.
Full textDing, Hong, and Fang Wu. "Image Guided Biodistribution and Pharmacokinetic Studies of Theranostics." Theranostics 2, no. 11 (2012): 1040–53. http://dx.doi.org/10.7150/thno.4652.
Full textAcar, Çigdem, Serap Teksöz, Perihan Ünak, F. Zümrüt Biber Müftüler, and E. Ilker Medine. "Somatostatin with 99mTc and Biodistribution Studies in Rats." Cancer Biotherapy and Radiopharmaceuticals 22, no. 6 (December 2007): 748–54. http://dx.doi.org/10.1089/cbr.2007.0340.
Full textDissertations / Theses on the topic "Biodistribution studies"
Kalofonos, Haralabos. "Radiolabelled monoclonal antibodies for tumour immunoscintigraphy and biodistribution studies." Thesis, Imperial College London, 1990. http://hdl.handle.net/10044/1/46376.
Full textMAGLIE, M. DE. "BIODISTRIBUTION AND TOXICITY OF METALLIC NANOPARTICLES:IN VIVO STUDIES IN MICE." Doctoral thesis, Università degli Studi di Milano, 2017. http://hdl.handle.net/2434/487404.
Full textJohnson, Claire. "Studies towards the synthesis of photosensitizers with improved biodistribution and light-absorbing properties." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp03/NQ27170.pdf.
Full textDubreil, Chloé. "Nanoparticules tolérogènes pour l’administration d’un auto-antigène des cellules bêta dans le diabète auto-immun Tolerogenic iron oxide nanoparticles in type 1 diabetes: biodistribution and pharmacokinetics studies in nonobese diabetic mice Tolerogenic nanoparticles boost regulatory B cells to reverse autoimmune diabetes." Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCB141.
Full textChronic autoimmune diseases are the consequence of self-antigens recognition as foreign by the adaptive immune system, resulting in inflammation and potential destruction of targeted tissues and organs. Type 1 diabetes (T1D) is one of the most common chronic autoimmune diseases. It is characterized by insulin deficiency due to selective destruction of insulin-producing beta-cells. At clinical onset, more than 70% of beta-cell mass can be destroyed. Consequently, early diagnosis is a major objective in order to avoid, limit or reverse autoimmune aggression, and to create opportunities for strategies enhancing beta-cell survival or regeneration. Antigen (Ag)-specific approaches are appealing because their effects are expected to be limited to cells expressing the chosen antigen, ideally the target organ. However, while treatment with beta -cell Ags can prevent disease in the model of the Non-Obese Diabetic (NOD) mouse, clinical trials in humans have produced disappointing results. Consequently, combinatorial approaches may be required for reversal and prevention of T1D. A potential strategy is to associate self-antigens with signals inducing a tolerogenic phenotype. Co-delivery ensures that both compounds get delivered at the same time and presented in the same cellular environment to auto-reactive immune cells. The first part of this work consisted in undertaking a thorough physicochemical characterization of a new drug vector, aiming to establish quantitative methods to optimize drug loading while maintaining biocompatibility and stability of the delivery vehicle. In this work, 9nm Ultra-small superparamagnetic iron-oxide (USPIO) nanoparticles were surface functionalized with phosphonate polyethylene glycol molecules (USPIO-PEG). Carboxylic acid functions were used to covalently bind a T1D autoantigen. PEG brush allows for the co-packaging of hydrophobic tolerogenic drug molecules, trapped between PEG chains through hydrophobic interactions. We carefully characterized protein and tolerogenic drug loading, and studied cell labeling, toxicity, integrity of loaded protein and tolerogenic drug, and activity of our nanoplatform on murine Bone Marrow Derived Dendritic Cells (BMDCs). We undertook biodistribution and pharmacokinetics studies using the NOD model that shares numerous features with human T1D. Biokinetic studies were performed both qualitatively using MRI 7T and histological Perls staining analyses and quantitatively using magnetometry for NP quantification. USPIO accumulate preferentially in NOD mice pancreas via Enhanced Permeability retention (EPR) effect thus, allowing us to distinguish pre-diabetic mice from non-diabetic controls. This result suggests that vascular leakage could be exploited for NP bioaccumulation, for therapeutic agent delivery and for imaging using MRI agents to monitor treatment. The second part of the work consisted in evaluating the therapeutic effect of such tolerogenic nanoparticles (NPS) on NOD diabetic mice. Diabetic mice were injected intravenously at diabetes onset. USPIO-PEG and vehicle treated mice reached 600mg/dL blood glucose level, considered limit for sacrificing mice, within a couple of days. NPs carrying either the tolerogenic drug or the autoantigen delayed diabetes progression up to 40 days. Complete NPs showed synergistic effects. In fact, 50% of treated mice were still alive 65 days after disease onset, and two mice reverted to stable normoglycemia for more than 300 days. To identify the underlying mechanism, the immune response to NPs in lymphoid organs was investigated. It was found that tolerogenic NPs induce splenomegaly mainly due to B cell proliferation. NP-stimulated B cells secrete anti-inflammatory cytokines namely IL-10 and TGF-beta. Similar B cells could be produced in vitro upon incubation of with NPs. Our strategy has promising therapeutic potential and could be applied, using relevant antigens, to a wider range of autoimmune diseases
Capolla, Sara. "Use of immune-nanoparticles containig chemiotherapeutic agents for the treatment of B-cell malignancies." Doctoral thesis, Università degli studi di Trieste, 2015. http://hdl.handle.net/10077/10980.
Full textB-cell malignancies are a heterogeneous group of clinical conditions including indolent diseases such as Chronic Lymphocytic Leukemia (CLL) and highly aggressive lymphoproliferative disorders such as Burkitt’s lymphoma. B-cell malignancies treatments take advantage of dose-intensive chemotherapeutic regimens and immunotherapy via monoclonal antibodies. Unfortunately, they may lead to insufficient tumor distribution of therapeutic agents and cause several adverse effects. Thus, we propose a novel therapeutic approach for the treatment of CLL and Burkitt’s lymphoma in which high-doses of the association of hydroxychloroquine and chlorambucil (HCQ/CLB) or fludarabine were loaded inside biodegradable nanoparticles (BNPs) coated with an anti-CD20 antibody. First of all, a Burkitt’s lymphoma cell line (BJAB), two CLL cell lines (MEC1 and EHEB) and cells purified from patients’ blood samples were used to confirm CD20 expression and to assess BNPs binding and internalization. These studies demonstrated BNPs ability to bind malignant B cells and to enter inside cells in a process different from endocytosis. Then, BNPs therapeutic effect was evaluated by MTT test, AnnV/PI assay and western blot to put in evidence apoptosis induction and autophagy inhibition. These experiments demonstrated drugs-loaded BNPs ability to kill malignant B cells with comparable effects than those obtained with free drugs whereas empty BNPs were practically ineffective. In vivo BNPs characterization included the evaluation of their toxicity, biodistribution and therapeutic effect. C57/BL mice were used to evaluate BNPs toxicity which was studied considering survival, loss of body weight and several tissue markers in the blood. Mice receiving 8 injections of free HCQ+CLB died in this experiment whereas animals challenged with the same amount of drugs encapsulated inside BNPs did not show toxic effects suggesting BNPs safety. The importance of antiCD20 antibody in the homing of BNPs was confirmed by in vivo Time-Domain Optical Imaging performed in localized B-cell malignancy-bearing mice. This analysis suggested the ability of antiCD20-conjugated BNPs to specifically target tumor B-cells, with a pick after 24-48 hours. On the contrary, untargeted BNPs localization inside tumor was significantly decreased. In this analysis it was also evident that the liver is the main site of BNPs’ elimination while in the other organs the presence of fluorescent BNPs was very low. Finally, BNPs ability to treat a new xenograft human/SCID leukemia and Burkitt’s lymphoma mouse model was studied. Drugs-loaded BNPs were able to improve HCQ/CLB efficacy in vivo allowing the cure of treated all Burkitt’s lymphoma-bearing mice and 3 out of 7 leukemia-bearing animals. All these data together put the basis for the potential use of BNPs in the treatment of B-cell malignancies.
I tumori a cellule B sono un gruppo eterogeneo di patologie che comprendono sia malattie indolenti, come la leucemia linfatica cronica (LLC), sia aggressive, come il linfoma di Burkitt. Il trattamento delle patologie a cellule B prevede sia l’utilizzo di chemioterapici (agenti alchilanti e analoghi delle purine) che di anticorpi monoclonali. Nonostante la varietà di terapie esistenti, l’efficacia di questi farmaci è limitata dalla mancata specificità per le cellule tumorali e dall’induzione di gravi effetti collaterali. Per ovviare ai limiti delle terapie attuali, è stato quindi proposto l’utilizzo di nanoparticelle coniugate con un anticorpo antiCD20, specifico per le cellule B, e contenenti alte concentrazioni di chemioterapici (idrossiclorochina e clorambucile o fludarabina). Le nanoparticelle sono state caratterizzate in vitro e in vivo durante questo progetto di dottorato. Inizialmente sono stati effettuati studi in vitro al fine di valutare l’espressione del CD20 sulla superficie di una linea cellulare di linforma di Burkitt (BJAB), due linee di LLC (MEC1 e EHEB) e cellule purificate da campioni di sangue di pazienti affetti da LLC. In seguito, il legame e l’internalizzazione delle nanoparticelle a queste cellule sono stati dimostrati suggerendo anche come le nanoparticelle vengano internalizzate attraverso un meccanismo diverso dall’endocitosi. L’effetto terapeutico in vitro delle nanoparticelle è stato valutato con test MTT, AnnessinaV/PI e tramite western blot al fine di evidenziare l’induzione di apoptosi e l’inibizione dell’autofagia, meccanismi attraverso cui i farmaci utilizzati sono noti agire. Questi esperimenti hanno dimostrato che le nanoparticelle cariche di chemioterapici sono in grado di uccidere le cellule B tumorali con effetti paragonabili a quelli ottenuti da pari concentrazioni di farmaci liberi dimostrando come il processo di produzione delle nanoparticelle non influisca sull’efficacia dei chemioterapici. Al contrario, nanoparticelle vuote non sono in grado di uccidere le cellule dimostrando la mancata tossicità dei polimeri da cui sono costituite. Dopo aver confermato il legame e l’internalizzazione delle nanoparticelle che inducono la morte delle cellule B tumorali, sono stati effettuati esperimenti in vivo tra cui studi di tossicità al fine di valutare eventuali effetti collaterali indotti dal trattamento, studi di biodistribuzione e la valutazione degli effetti terapeutici. Gli studi di tossicità sono stati effettuati in topi sani valutando parametri quali la perdita di peso, la sopravvivenza e la tossicità sistemica. Nanoparticelle cariche di farmaci presentano un profilo tossicologico sicuro mentre pari dosi di farmaci liberi inducono la morte di tutti gli animali trattati. Questi esperimenti dimostrano quindi come l’inserimento di farmaci all’interno di nanoparticelle prevenga gli effetti collaterali normalmente indotti dai chemioterapici. Secondariamente, sono stati effettuati studi di biodistribuzione di nanoparticelle coniugate o meno con un anticorpo antiCD20. Questi studi effettuati tramite Optical Imaging dimostrano come nanoparticelle coniugate con l’anticorpo antiCD20 si localizzino preferenzialmente nella massa tumorale in 24-48 ore in quantità maggiore rispetto a nanoparticelle non coniugate con l’anticorpo. Inoltre, da queste analisi risulta evidente come il fegato sia il maggiore sito di eliminazione delle nanoparticelle mentre in altri organi la presenza di nanoparticelle è molto bassa. Infine, un modello disseminato di linfoma di Burkitt e un modello di LLC sono stati sviluppati in topi SCID (Severe Combined ImmunoDeficiency) iniettando rispettivamente cellule BJAB intraperitoneo e cellule MEC1 endovena. I modelli sono stati caratterizzati e utilizzati per valutare la potenziale applicazione delle nanoparticelle nel trattamento di queste patologie. Questi studi hanno dimostrato come le nanoparticelle siano in grado di aumentare l’efficacia dei chemioterapici e di curare tutti i topi affetti da linfoma di Burkitt e 3/7 topi affetti da leucemia. Concludendo, questi risultati suggeriscono la potenziale applicazione delle nanoparticelle cariche di chemioterapici nel trattamento di LLC e linfoma di Burkitt.
XXVII Ciclo
1986
Johnson, Claire. "Studies towards the synthesis of photosensitizers with improved biodistribution and light-absorbing properties." Thesis, 1997. http://hdl.handle.net/2429/8672.
Full textYeh, Shih-Hua, and 葉士華. "Fluorescent Nanodiamond as a Novel Nanoparticle for Cell Labeling and in vivo Biodistribution Studies." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/16969705787253390340.
Full text國立臺灣大學
化學研究所
99
Fluorescent nanodiamond (FND) has many unique properties, such as photostability and biocompatibility, making it as a novel nanoparticle for both in vitro and in vivo applications. By high energy ion beam irradiation on 100 nm typeIb nanodiamonds and subsequent annealing at high temperature, result in NV0 and NV- defect centers in the diamond crystal lattice which emit far red fluorescence under the excitation of visible light. Excellent optical properties like no photobleaching and no photoblinking along with facile surface fuctionalizabilty and nontoxicity make FND a robust nanoparticle for cell labeling and tracking. Here, we demonstrated that the 100 nm FND as a nanolabel for Hela (adherent cervical cancer cell) and M1 (non-adherent leukemia cell). We introduced FNDs into cells through incubation. Colocalization analysis showed that the internalized FNDs are accumulated in lysosomes with little excretion after 3 hours of post-labeling for Hela cells. Cell division tracking was performed by fluorescence microscopy and cell doubling time was analyzed by flow cytometry. Compared to molecular fluorophore, carboxyfluorescein diacetate succinimidyl ester, FND offers several advantages in long-term cell labeling and tracking. Finally, we demonstrated the long-term in vivo biodistribution of FNDs. FNDs accumulated in liver and spleen after intraperitoneal injection during the study period of 5 months, showing no symptoms of abnormality. The photostability of FND in vivo is also shown here through in vivo imaging system. In conclusion, FND is an ideal nanoparticle for various biological applications.
Biagiotti, Giacomo. "Discovery of a Drug Delivery System Based on Carbon Nanotubes: Synthesis and Biological Studies." Doctoral thesis, 2019. http://hdl.handle.net/2158/1158681.
Full textChen, Chien-Yu, and 陳建宇. "Synthesis, Biodistribution, and SPECT/CT Imaging Studies of 99mTc Labeled Angiogenesis-targeting polyplexes for gene delivery." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/62607642058396471728.
Full text國立清華大學
生醫工程與環境科學系
98
The polyplexes of polyethylene glycol (PEG) grafted polyethylenimine (PEI) and conjugated with gene can be used as a gene carrier in gene therapy for its low toxicity. However, the polyplexes displayed lower transfection capability in vitro and in vivo in the past studies. Modification of the polyplexes by binding a targeting ligand may improve the transfection capability. Integrin αvβ3 plays a critical role in tumor angiogenesis and becomes a promising diagnostic and therapeutic target for various solid tumors. It is well known that Arg-Gly-Asp (RGD) peptide has high affinity with αvβ3 integrin. The studies of targeting ability of a gene delivery vehicle usually rely on a design by expression of reporter gene in vivo. In this study, we have attempted to label a targeting gene delivery vehicle with a gamma emitter for evaluating its biodistribution and targeting ability by single photon emission computed tomography/computed tomography (SPECT/CT). The scope of this study was to prepare targeting polymeric gene carriers based on dimeric cyclic RGD binding PEG-g-PEI (abbreviated as E[c(RGDyK)]2- PEG-g-PEI) and labeling with 99mTc for in vivo study. We have prepared the PEG-g-PEI products with PEG to PEI ratios of 1 to 1, 3 to 1, and 10 to 1, abbreviated as PP1, PP3 and PP10, respectively. The PEG to PEI ratios in the products were confirmed by 1H-NMR. Furthermore, the PEG-g-PEI/DNA polyplexes with different polymer/DNA weight ratios (abbreviated as P/D) were prepared and their surface charges and zeta potentials and formation abilities with DNA were measured. The particles sizes of the PEG-g-PEI/DNA polyplexes were measured to be 90-135 nm. The zeta potential of the polyplexes was measured to be 40-50 mV. The polyplexes had high formation ability with DNA in P/D ratio at 1:1. We compared the cytotoxicities of PEI/DNA and PEG-g-PEI/DNA fabricated at different PEG/PEI ratios and different P/D ratios. The polyplex of PEG-g-PEI/DNA fabricated with PEG/PEI ratio at 10: 1 and P/D=1, i.e., PP10/D, showed lowest cytotoxicity whereas PEI/DNA showed highest cytotoxicity. In the transfection studies, PP10/D with PP10 concentration at 0.025 mg/ml displayed a highest transfection efficiency in comparison with the other two polyplexes. The RPP10/D polyplex demonstrated significantly higher binding affinity and transfection efficiency than non-targeting PP10/D. Both PP10/D and RPP10/D had high radiolabeling efficiency at greater than 95% and borne with radiochemical stability above 80% either in saline and in rat plasma when stored for 24 h. In in vivo SPECT/CT studies, it was found from the images that RPP10/D presented higher uptake in the tumor than PP10/D through all the postinjection times studied. From the analyses on the regions of interest (ROI) by the SPECT/CT imaging, RPP10/D also showed higher tumor to liver and tumor to blood ratios than PP10/D. The conventional biodistribution study presented corresponding results and confirmed the targeting effect of RPP10/D. The plasmid EGFP (enhanced green fluorescent protein) of RPP10/D for gene transfection was also observed to successfully transfect into the tumor site by fluorescence microscope in this study. In conclusion, E[c(RGDyK)]2 bound PEGylated PEI complex is a potential gene delivery vehicle as a targeting and imaging agent for gene therapy as evidenced by the study with the Hela tumor bearing mice model.
Serralheiro, Ana Isabel Azevedo. "Intranasal Delivery of Antiepileptic Drugs: Non-clinical Evaluation of Pharmacokinetics and Brain Biodistribution." Doctoral thesis, 2016. http://hdl.handle.net/10316/29482.
Full textEven though remarkable advances in the treatment of epilepsy have been made over the last years, the currently available anticonvulsant pharmacotherapy is unsatisfactory as it provides only the management of epileptic seizures, is not effective in a significant percentage of patients, and is often associated to several adverse effects. Therefore, the development of novel and alternative therapeutic approaches towards a safer and more effective seizure control is urgently needed. The search for an ideal antiepileptic drug (AED) that will be capable of preventing, delaying or modifying epilepsy is still ongoing. However, since the process of discovery and development of new chemical entities is very expensive and commonly accompanied by reduced rates of success, the use of already existing AEDs by improving some of their formulation properties, delivery systems or routes of administration aiming at allowing their efficient and prompt delivery to the brain could also be an attractive strategy. Owing to the unique anatomical connection between the nasal cavity and the central nervous system, a great deal of interest has recently been focused on the exploitation of the intranasal (IN) route for the delivery of therapeutics directly to the brain by circumventing the blood-brain barrier (BBB). Indeed, the olfactory region is the only site in the human body where the nervous system is in direct contact with the surrounding environment, providing a great opportunity for drugs intranasally administered to gain a quick and easy access to the brain, minimising their systemic exposure. The purpose of the present thesis was to assess and compare the pharmacokinetic behaviour of phenytoin (PHT), carbamazepine (CBZ), oxcarbazepine (OXC) and lamotrigine (LTG) administered via the IN and intravenous (IV) routes to mice and to investigate whether a direct transport of the referred compounds from nose to brain could be involved. This project started with the development and validation of appropriate and reliable bioanalytical techniques to support the execution of the intended pharmacokinetic and brain biodistribution studies. In essence, two high performance liquid chromatographic methods coupled with ultraviolet detection were properly validated for the quantification of drugs and some of their respective main metabolites in mouse plasma, brain (whole brain, olfactory bulb and frontal cortex) and liver matrices. An additional technique developed in human plasma has also shown to be a useful tool to be applied in clinical practice. Due to unexpected difficulties encountered during the definition and optimisation of the in vivo experimental setup, two of the four initially proposed test molecules were excluded from further investigation, which was performed only with CBZ and LTG. The fairly comparable concentration-time profiles of both of these drugs obtained in plasma, brain and liver following IN and IV administrations to mice, together with a high IN absolute bioavailability, underscored the fact that a substantial absorption of the drugs from the nasal vasculature into the systemic circulation has occurred. Conversely, the uneven biodistribution profile after IN delivery of either CBZ or LTG, with the highest drug concentration levels attained in the olfactory bulb contrasted with the homogeneous biodistribution pattern typically observed following IV injection, strongly suggesting the involvement of a pathway to directly transport these drugs from nose-to-brain, bypassing the BBB. According to our results, it seems that the IN route can be assumed as a suitable and a valuable drug delivery strategy for the chronic treatment of epilepsy and, in the specific case of CBZ, it gathers favourable conditions to be also applied in acute convulsive emergencies. Considering all its inherent potential and indisputable advantages, the IN administration may likewise emerge as a promising and a non-invasive alternative approach for a prospective management of pharmacoresistance.
Apesar de, ao longo dos últimos anos, terem sido alcançados avanços notáveis no que ao tratamento da epilepsia diz respeito, a terapêutica farmacológica anticonvulsivante atualmente disponível não é satisfatória, uma vez que possibilita apenas o controlo das crises epiléticas, não é eficaz numa percentagem muito significativa de doentes e é frequentemente associada a vários efeitos adversos. Deste modo, afigura-se urgente o desenvolvimento de abordagens terapêuticas novas e alternativas com vista a um controlo mais seguro e eficaz das crises. A procura pelo fármaco antiepilético (AED) ideal que permita prevenir, retardar ou modificar a doença ainda permanece uma realidade. Porém, tendo em conta que o processo de descoberta e desenvolvimento de novas entidades químicas é geralmente muito dispendioso e acompanhado de uma reduzida taxa de sucesso, a otimização das propriedades de formulação, sistemas de entrega ou vias de administração de AEDs já estabelecidos e disponíveis na clínica também poderá constituir uma estratégia muito atrativa. A ligação anatómica ímpar entre a cavidade nasal e o sistema nervoso central tem recentemente suscitado um interesse particular na exploração da via intranasal (IN) para a entrega de agentes terapêuticos diretamente para o cérebro, circunscrevendo a barreira hemato-encefálica (BBB). De facto, a região olfativa representa o único local do corpo humano onde o sistema nervoso se encontra em contacto direto com o meio ambiente, oferecendo assim uma grande oportunidade aos fármacos administrados por via IN de atingirem o cérebro de uma forma rápida e facilitada, minimizando a sua exposição sistémica. Com o trabalho de investigação subjacente à presente dissertação pretendeu-se avaliar e comparar o comportamento farmacocinético da fenitoína (PHT), carbamazepina (CBZ), oxcarbazepina (OXC) e lamotrigina (LTG) administrados por via IN e intravenosa (IV) a murganhos, e investigar o eventual envolvimento de um transporte direto para estas moléculas desde a cavidade nasal até ao cérebro. Este projeto iniciou-se com o desenvolvimento e validação de técnicas bioanalíticas adequadas e confiáveis para suportar a execução dos estudos farmacocinéticos e de biodistribuição cerebral pretendidos. Para tal, foram validados dois métodos de cromatografia líquida de alta eficiência acoplada a deteção ultravioleta para a quantificação dos referidos fármacos e alguns dos seus principais metabolitos em matrizes de plasma, cérebro (cérebro total, bolbo olfativo e córtex frontal) e fígado de murganho. Uma técnica adicional em plasma humano foi ainda desenvolvida demonstrando aplicabilidade na prática clínica. Face a dificuldades inesperadamente encontradas durante a definição e otimização do protocolo experimental in vivo, apenas a CBZ e a LTG, de entre as quatro moléculas teste inicialmente propostas, foram amplamente avaliadas neste trabalho. A semelhança observada entre os perfis de concentração-tempo em plasma, cérebro e fígado após a administração IN e IV a murganhos, juntamente com a elevada biodisponibilidade absoluta IN indicaram a ocorrência de uma absorção substancial de ambos os fármacos a partir da vasculatura nasal para a circulação sanguínea. Por outro lado, em oposição a um padrão de biodistribuição cerebral homogéneo tipicamente observado mediante administração IV, após administração IN foi obtido um perfil muito heterogéneo com níveis de concentração de CBZ e LTG mais elevados no bolbo olfativo, sugerindo assim o provável envolvimento de uma via de transporte direto desde a cavidade nasal até ao cérebro contornando a BBB. De acordo com os nossos resultados, pressupõe-se que a via IN seja assumida como uma estratégia válida e apropriada para a administração continuada de ambos os fármacos visando o tratamento crónico da epilepsia, reunindo no caso específico da CBZ condições favoráveis para ser aplicada também em situações de emergência convulsiva. Considerando todas as suas vantagens e potencial inerente, a administração IN poderá igualmente representar uma abordagem alternativa, não-invasiva e promissora para um controlo prospetivo da epilepsia farmacorresistente.
FCT - SFRH/BD/64895/2009
Book chapters on the topic "Biodistribution studies"
Deshmukh, Aaishwarya, Jayvadan Patel, Govind Vyas, and Mukesh Patel. "In Vivo Biodistribution and Pharmacokinetic Studies of NPDDS for Brain Targeting." In Pharmacokinetics and Pharmacodynamics of Nanoparticulate Drug Delivery Systems, 365–84. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-030-83395-4_20.
Full textKlingensmith, William C. "Overview of Part III, Quantitative Evaluation in Nuclear Medicine Studies." In The Mathematics and Biology of the Biodistribution of Radiopharmaceuticals - A Clinical Perspective, 129–37. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-26704-3_11.
Full textRaki, Mari, Kim Bergström, and Jukka Jolkkonen. "In Vivo Biodistribution Studies and Cell Tracking in Stroke Using SPECT Imaging." In Cell-Based Therapies in Stroke, 137–49. Vienna: Springer Vienna, 2012. http://dx.doi.org/10.1007/978-3-7091-1175-8_10.
Full textMoisan, A., PY Le Prise, J. Le Cloirec, E. Legall, C. Ghandour, R. Le Blay, and JY Herry. "111-Indium Labeled Platelets in Thrombocytopenic Purpura. Survival and Biodistribution Studied With Scintillation Camera. A Review of 485 Patients." In Clinical Application of Radiolabelled Platelets, 248–57. Dordrecht: Springer Netherlands, 1990. http://dx.doi.org/10.1007/978-94-009-0581-8_22.
Full textHodges, Robert. "Clinical Considerations in Radiotracer Biodistribution Studies." In Biological Transport of Radiotracers, 261–71. CRC Press, 2020. http://dx.doi.org/10.1201/9780429283062-13.
Full textKumar Gupta, Santosh, and Venkatesh Rangarajan. "Radiopharmaceutical Biodistribution and Dosimetry." In Radiopharmaceuticals - Current Research for Better Diagnosis and Therapy [Working Title]. IntechOpen, 2022. http://dx.doi.org/10.5772/intechopen.104917.
Full textLahkar, Sunita, and Malay K. Das. "Image-guided Biodistribution and pharmacokinetic studies of theranostics." In Multifunctional Theranostic Nanomedicines in Cancer, 293–306. Elsevier, 2021. http://dx.doi.org/10.1016/b978-0-12-821712-2.00009-8.
Full textSharma, Nivya, Mohd Aslam Saifi, Shashi Bala Singh, and Chandraiah Godugu. "In vivo studies: toxicity and biodistribution of nanocarriers in organisms." In Nanotoxicity, 41–70. Elsevier, 2020. http://dx.doi.org/10.1016/b978-0-12-819943-5.00003-8.
Full textWani, Irshad Ahmad. "Biomedical Applications of Gold Nanoparticles." In Biomedical Engineering, 837–58. IGI Global, 2018. http://dx.doi.org/10.4018/978-1-5225-3158-6.ch037.
Full textWani, Irshad Ahmad. "Biomedical Applications of Gold Nanoparticles." In Integrating Biologically-Inspired Nanotechnology into Medical Practice, 74–101. IGI Global, 2017. http://dx.doi.org/10.4018/978-1-5225-0610-2.ch004.
Full textConference papers on the topic "Biodistribution studies"
Moan, Johan, Qian Peng, Vladimir Iani, Li Wei Ma, Richard W. Horobin, Kristian Berg, Magne Kongshaug, and Jahn M. Nesland. "Biodistribution, pharmacokinetic, and in-vivo fluorescence spectroscopic studies of photosensitizers." In BiOS Europe '95, edited by Benjamin Ehrenberg, Giulio Jori, and Johan Moan. SPIE, 1996. http://dx.doi.org/10.1117/12.231008.
Full textEustaquio, Trisha, and James F. Leary. "Nanobarcoding: a novel method of single nanoparticle detection in cells and tissues for nanomedical biodistribution studies." In SPIE NanoScience + Engineering, edited by Hooman Mohseni, Massoud H. Agahi, and Manijeh Razeghi. SPIE, 2011. http://dx.doi.org/10.1117/12.893915.
Full textMansfield, James, Abhi Agarwal, Allison Curtis, and Thomas Krucker. "Abstract 4211:In vivofluorescence kinetic imaging for improved contrast and studies of temporal and quantitative biodistribution." In Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-4211.
Full textTartis, Michaelann S., Jan Marik, Azadeh Kheirolomoom, Rachel E. Pollard, Hua Zhang, Jinyi Qi, Julie L. Sutcliffe, and Katherine W. Ferrara. "Pharmacokinetics of Encapsulated Paclitaxel: Multi-Probe Analysis With PET." In ASME 2007 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2007. http://dx.doi.org/10.1115/sbc2007-176435.
Full textShah, Neha B., and John C. Bischof. "Effect of Surface Charge on Gold Nanoparticle Biotransport: An In Vivo Blood and Biodistribution Study." In ASME 2011 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2011. http://dx.doi.org/10.1115/sbc2011-53324.
Full textHe, Guangan, Gregory Thiabaud, Kathyrin A. Shelton, Luke J. Segura, Jonathan L. Sessler, Rick A. Finch, Zahid H. Siddik, and Jonathan F. Arambula. "Abstract 1073: Preclinical tissue biodistribution and plasma pharmacokinetic studies with oxaliTEX, a novel platinum(IV)-based oxaliplatin prodrug." In Proceedings: AACR Annual Meeting 2021; April 10-15, 2021 and May 17-21, 2021; Philadelphia, PA. American Association for Cancer Research, 2021. http://dx.doi.org/10.1158/1538-7445.am2021-1073.
Full textTsygankova, А., V. Каnygin, А. Каsatova, Е. Zavjalov, Т. Guselnikova, А. Kichigin, and R. Mukhamadiyarov. "PRE-CLINICAL BNCT GLIOBLASTOMA RESEARCH. ICP-AES BORON DETERMINATION METHOD. STUDIES ON 10 B BORON BIODISTRIBUTION IN MICE’S ORGANS." In RAP Conference. Sievert Association, 2020. http://dx.doi.org/10.37392/rapproc.2019.06.
Full textGupta, Parul, Dangshe Ma, Rachel Roach, Mary Spilker, Mauricio Leal, Cedo Bagi, and Anand Giddabasappa. "Abstract 2092: Characterizing NIR dye-IL13RA2 antibody conjugates for biodistribution studies in xenograft tumor models by fluorescence molecular tomography (FMT)." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-2092.
Full textNizzero, Sara, Feng Li, Alessandro Venuta, Guodong Zhang, Carlotta Borsoi, Joy Wolfram, Junhua Mai, et al. "Abstract LB-019: Empowering preclinical studies: A systematic and quantitative analysis of biodistribution methods to facilitate clinical translation of new drugs." In Proceedings: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, IL. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1538-7445.am2018-lb-019.
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