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Computational and experimental studi...
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Raman, Chandrashekar.
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Computational and experimental studies of controlled release drug delivery: Effect of microsphere diameter and drug size on in-vitro release kinetics.
Record Type:
Electronic resources : Monograph/item
Title/Author:
Computational and experimental studies of controlled release drug delivery: Effect of microsphere diameter and drug size on in-vitro release kinetics./
Author:
Raman, Chandrashekar.
Description:
107 p.
Notes:
Source: Dissertation Abstracts International, Volume: 66-07, Section: B, page: 3836.
Contained By:
Dissertation Abstracts International66-07B.
Subject:
Engineering, Chemical. -
Online resource:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3182359
ISBN:
9780542230714
Computational and experimental studies of controlled release drug delivery: Effect of microsphere diameter and drug size on in-vitro release kinetics.
Raman, Chandrashekar.
Computational and experimental studies of controlled release drug delivery: Effect of microsphere diameter and drug size on in-vitro release kinetics.
- 107 p.
Source: Dissertation Abstracts International, Volume: 66-07, Section: B, page: 3836.
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2005.
The use of devices for controlled release therapeutics is a thriving area of research today. Among the many controlled release devices available, poly(lactide-co-glycolide) (PLG) microspheres are perhaps the most popular. While a number of studies have investigated the effects of various parameters on the in-vitro release kinetics from microspheres, detailed studies of the effect of microsphere size have not been presented. This work is an examination of the effect of microsphere size on the in-vitro release kinetics of small-molecule drugs, proteins and oligonucleotides from uniform PLG microspheres.
ISBN: 9780542230714Subjects--Topical Terms:
1018531
Engineering, Chemical.
Computational and experimental studies of controlled release drug delivery: Effect of microsphere diameter and drug size on in-vitro release kinetics.
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Computational and experimental studies of controlled release drug delivery: Effect of microsphere diameter and drug size on in-vitro release kinetics.
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107 p.
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Source: Dissertation Abstracts International, Volume: 66-07, Section: B, page: 3836.
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Adviser: Daniel W. Pack.
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Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2005.
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The use of devices for controlled release therapeutics is a thriving area of research today. Among the many controlled release devices available, poly(lactide-co-glycolide) (PLG) microspheres are perhaps the most popular. While a number of studies have investigated the effects of various parameters on the in-vitro release kinetics from microspheres, detailed studies of the effect of microsphere size have not been presented. This work is an examination of the effect of microsphere size on the in-vitro release kinetics of small-molecule drugs, proteins and oligonucleotides from uniform PLG microspheres.
520
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For small-molecule release, increasing the microsphere diameter slows the release and the profile shifts from smooth, diffusive profile to sigmoidal profile. A model incorporating the effects of polymer degradation and the non-uniform initial drug distribution within the microspheres is developed to describe this transition. The variation of the drug's diffusivity with polymer molecular weight is also included. The model results agree well with experimental data despite using only one fit parameter.
520
$a
In the case of in-vitro protein (human hemoglobin) and oligonucleotide release, an unusual phenomenon of faster release from larger microspheres is observed. Using polymer characterization techniques, larger microspheres are shown to degrade and erode faster, which explains the faster macromolecule release from them. The faster degradation of larger microspheres is believed to be due to the accumulation of acidic degradation products within the microspheres, which are known to further catalyze PLG degradation.
520
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In order to verify the accumulation of acidic degradation products within larger microspheres, the pH within microspheres was monitored by encapsulating bovine serum albumin labeled with pH-sensitive and pH-insensitive fluorophores. Ratiometric confocal microscopy gives us a direct measure of the pH of the local environment. From these experiments, the increased acidity within larger microspheres is demonstrated.
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Overall, the several ways microsphere size affects small-molecule, protein and oligonucleotide release have been clarified in this work.
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School code: 0090.
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http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3182359
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