رسالة جامعية
Polymeric nanocarriers for the enhancement of enzyme replacement therapy in lysosomal storage diseases: A proof of concept study
| العنوان: | Polymeric nanocarriers for the enhancement of enzyme replacement therapy in lysosomal storage diseases: A proof of concept study |
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| المؤلفون: | Román-Martínez, Angélica |
| المساهمون: | Latorre-Esteves, Magda, College of Engineering, Almodovar, Jorge, Torres-Lugo, Madeline, Department of Chemical Engineering, Cortes-Figueroa, José E. |
| سنة النشر: | 2016 |
| المجموعة: | Digital Institutional Repository @UPR (University of Puerto Rico - DiRe.UPR) |
| مصطلحات موضوعية: | Nanoparticle drug delivery systems, Biodegradable synthetic polymers, Lysosomal Storage Diseases, Enzyme Replacement Therapy, Lysosomal storage diseases--Treatment, Drug delivery systems, Block copolymers, Enzymes--Therapeutic use |
| الوصف: | Lysosomal Storage Diseases (LSDs) are a group of inheritable genetic diseases caused by mutant lysosomal enzymes, leading to the accumulation of undigested macromolecules in the lysosomes and causing increases in lysosome size and number, cellular dysfunction, clinical abnormalities and premature death. These LSDs can be treated with Enzyme Replacement Therapy (ERT) through intravenous administration of a recombinant enzyme in replacement of the defective enzyme. However, this is an expensive and inefficient method with adverse side effects associated with the high enzyme amounts required for the treatment, the need of posttranslational modification of the enzyme and the host immune system response. Nanoparticle drug delivery systems (DDSs) are a promising alternative to enclose the therapeutic cargo, then overcoming the drawbacks associated with ERT. As building blocks of those DDSs, biodegradable synthetic polymers are considered an attractive alternative for protein delivery applications because they can be designed to obtain desirable properties like low immune response, stimuli response, specific circulation time and affinity to certain drugs and environments. This research project aims to develop biodegradable and bioresponsive polymersomes, composed of amphiphilic block copolymers of Polyethylene glycol and Polycaprolactone (PEGPCL), suitable for the encapsulation and delivery of protein therapeutics as proof of concept for ERT applications. This goal was achieved through the synthesis and optimization of protein loaded polymersomes using a Water in-Oil-in Water (WOW) double emulsion method, and the addition of a protein corona composed of Fetal Bovine Serum (FBS) components. First, a group of copolymers were synthesized by Ring Opening Polymerization, using either Stannous Octoate (SO) or Hydrochloric Acid (HCl) as catalysts. Characterization was carried out by Proton Nuclear Magnetic Resonance (1H-NMR) and Gel Permeation Chromatography (GPC). Results demonstrated that SO was a better catalyst for ... |
| نوع الوثيقة: | thesis |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://hdl.handle.net/20.500.11801/487Test |
| الإتاحة: | https://doi.org/20.500.11801/487Test https://hdl.handle.net/20.500.11801/487Test |
| حقوق: | (c) 2016 Angélica Román-Martinez ; All rights reserved |
| رقم الانضمام: | edsbas.779ACB9F |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |