Fabrication and characterization of controlled release of proteins and peptides from poly glu lactide-co-glycolide (PLGA) microspheres /
Biodegradable poly(lactide-co-glycolide) (PLGA)-based microspheres and nanoparticles have received much attention over the last twenty-five years for controlled parenteral delivery of therapeutic protein and peptide drugs. In general, PLGA-based injectable delivery systems of macromolecular protein...
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| Main Author: | |
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| Format: | Thesis |
| Language: | English |
| Published: |
Kuantan, Pahang :
Kulliyyah of Pharmacy, International Islamic University Malaysia,
2016
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| Online Access: | Click here to view 1st 24 pages of the thesis. Members can view fulltext at the specified PCs in the library. |
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| LEADER | 050550000a22003010004500 | ||
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| 008 | 160905s2016 my a f m 000 0 eng d | ||
| 040 | |a UIAM |b eng |e rda | ||
| 041 | |a eng | ||
| 043 | |a a-my--- | ||
| 050 | 0 | 0 | |a RS201.M53 |
| 100 | 1 | |a Ansary, Md. Rezaul Haque, |e author | |
| 245 | 1 | |a Fabrication and characterization of controlled release of proteins and peptides from poly glu lactide-co-glycolide (PLGA) microspheres / |c by Md. Rezaul Haque Ansary | |
| 264 | 1 | |a Kuantan, Pahang : |b Kulliyyah of Pharmacy, International Islamic University Malaysia, |c 2016 | |
| 300 | |a xviii, 208 leaves : |b illustrations ; |c 30cm. | ||
| 336 | |2 rdacontent |a text | ||
| 502 | |a Thesis (Ph.D)--International Islamic University Malaysia, 2016. | ||
| 504 | |a Includes bibliographical references (leaves 180-200). | ||
| 520 | |a Biodegradable poly(lactide-co-glycolide) (PLGA)-based microspheres and nanoparticles have received much attention over the last twenty-five years for controlled parenteral delivery of therapeutic protein and peptide drugs. In general, PLGA-based injectable delivery systems of macromolecular protein and peptide drugs still suffer from two major technical problems associated with their inherent stability problem. Initial burst release followed by very slow and incomplete release is one of the most serious problems in the formulation of PLGA-based protein drugs delivery system. In this study, two model proteins, bovine serum albumin (BSA) and lysozyme, and a therapeutic peptide drug, insulin loaded double-walled microspheres have been fabricated using a fast degrading glucose core, hydroxyl-terminated poly(lactide-co-glycolide) (Glu-PLGA) and a moderate degrading carboxyl-terminated PLGA polymers to reduce the high initial burst release and to eliminate the lag phase from the release profile of PLGA microspheres. Double-walled microspheres were prepared using a modified water-in-oil-in-oil-in-water (w1/o/o/w2) method. In addition, single-polymer microspheres were prepared by a conventional water-in-oil-in-water (w1/o/w2) emulsion solvent evaporation method for comparison. The microspheres size, morphology, encapsulation efficiency, thermal properties, in vitro drug release, and structural integrity of BSA, lysozyme and insulin were evaluated in this study. The bioactivity of released lysozyme was determined using Micrococcus lysodeikticus as substrate. Moreover, in vivo release and bioactivity of insulin was evaluated upon subcutaneous injection of insulin loaded microspheres in STZ induced diabetic rats. BSA, lysozyme and insulin loaded double-walled microspheres prepared with Glu-PLGA and PLGA polymers in a mass ratio of 1:1 showed reduced particle size (< 5 µm), non-porous, smooth-surfaced, and spherical in shape. In contrast, highly porous surface was observed for single-polymer microspheres. Double-walled microspheres comprising Glu-PLGA and PLGA polymers in a mass ratio of 1:1 exhibited higher encapsulation efficiency for BSA compared to lysozyme and insulin. A significant reduction in initial burst release was achieved for double-walled microspheres compared to single-polymer microspheres. In addition, double-walled microspheres prepared using Glu-PLGA and PLGA polymers in a mass ratio of 1:1 exhibited continuous and almost complete release of BSA and insulin after small initial burst release without any lag phase. In contrast, incomplete release was observed for lysozyme from both double-walled and single-polymer microspheres. SDS-PAGE result shows that a small fraction of encapsulated and released proteins (BSA and lysozyme) underwent aggregation and possible degradation, whereas no substantial aggregation or degradation was observed for insulin during microspheres fabrication and in vitro release studies. Moreover, the in vivo studies demonstrated that the bioactivity of insulin was retained throughout the experimental period. This study suggests that double-walled microspheres made of Glu-PLGA and PLGA polymers in a mass ratio of 1:1 can be a potential delivery system for pharmaceutical proteins and peptides. | ||
| 596 | |a 1 6 | ||
| 655 | 7 | |a Theses, IIUM local | |
| 690 | |a Dissertations, Academic |x Kulliyyah of Pharmacy |z IIUM | ||
| 710 | 2 | |a International Islamic University Malaysia. |b Kulliyyah of Pharmacy | |
| 856 | 4 | |u https://lib.iium.edu.my/mom/services/mom/document/getFile/lmNKfJzXsOWWLVhjhcjBQuduT8LcvBIx20170112145505975 |z Click here to view 1st 24 pages of the thesis. Members can view fulltext at the specified PCs in the library. | |
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