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Novel multifunctional polyelectrolyt...
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Taluja, Ajay.
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Novel multifunctional polyelectrolytes in protein stabilization and controlled delivery.
紀錄類型:
書目-電子資源 : Monograph/item
正題名/作者:
Novel multifunctional polyelectrolytes in protein stabilization and controlled delivery./
作者:
Taluja, Ajay.
出版者:
Ann Arbor : ProQuest Dissertations & Theses, : 2008,
面頁冊數:
189 p.
附註:
Source: Dissertation Abstracts International, Volume: 69-02, Section: B, page: 9660.
Contained By:
Dissertation Abstracts International69-02B.
標題:
Pharmaceutical sciences. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3302499
ISBN:
9780549481799
Novel multifunctional polyelectrolytes in protein stabilization and controlled delivery.
Taluja, Ajay.
Novel multifunctional polyelectrolytes in protein stabilization and controlled delivery.
- Ann Arbor : ProQuest Dissertations & Theses, 2008 - 189 p.
Source: Dissertation Abstracts International, Volume: 69-02, Section: B, page: 9660.
Thesis (Ph.D.)--The University of Utah, 2008.
This dissertation focused on evaluation of multifunctional novel polyelectrolytes for stabilization of proteins in poly(lactide-co-glycolide) [PLGA] microspheres. The research project focused on ion-pairing proteins with polyelectrolytes to improve microspheres fabrication, characteristics, and performance in a simulated physiological environment.
ISBN: 9780549481799Subjects--Topical Terms:
3173021
Pharmaceutical sciences.
Novel multifunctional polyelectrolytes in protein stabilization and controlled delivery.
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This dissertation focused on evaluation of multifunctional novel polyelectrolytes for stabilization of proteins in poly(lactide-co-glycolide) [PLGA] microspheres. The research project focused on ion-pairing proteins with polyelectrolytes to improve microspheres fabrication, characteristics, and performance in a simulated physiological environment.
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Ion-pairing of anionic poly(ethylene glycol)-block-oligo(vinyl sulfadimethoxine) [PEG-OVSDM] with cationic lysozyme and the effect on reduction of protein's aggregation during encapsulation in microspheres was investigated. Lysozyme recovery after interfacial exposure (42--88%) was PEG-OVSDM concentration-dependent compared to only 30% for lysozyme without any ion-pairing. No significant structural or activity changes in the recovered lysozyme were observed by enzymatic assay, fluorescence, and chromatographic methods. Lysozyme and PEG-OVSDM ion-paired in an optimized weight ratio were incorporated into microspheres via the double emulsion method. Incorporation of lysozyme complexes led to greater retention of protein stability in the PLGA microspheres, higher encapsulation efficiency and loading amount, compared to the control microspheres. More significantly, ion-pairing was able to dramatically reduce the initial burst and provided an overall better control of release rate of lysozyme.
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Along the same principle, a cationic polyelectrolyte; poly(ethylene glycol)- block-poly(L-histidine) [PEG-PH] was tested for stabilization of insulin during microencapsulation. The effect of nonionic Pluronic F-127 as a control and PEG-PH as a novel excipient was evaluated at various insulin/polymer weight ratios.
520
$a
PEG-PH complexation with insulin at pH 6.0 drastically reduced protein aggregation. Circular dichroism revealed negligible change in soluble insulin's secondary structure. Radioimmunoassay showed that recovered insulin had retained its immunoreactivity. Incorporation of insulin/PEG-PH complexes led to modest benefits compared to the control insulin microspheres. Ion-pairing was not able to modulate the release of insulin from microspheres possibly due to weak interactions between insulin and PEG-PH. Insignificant hydrophobic interactions did not lead to coacervation; most likely a key determinant in successful use in microencapsulation as demonstrated by PEG-OVSDM/lysozyme system.
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Optimization of ionic and hydrophobic interactions between the proteins and polyelectrolytes needs to be determined empirically. Manipulation of polyelectrolyte-protein complexation may play a role in controlled delivery of proteins from polymeric matrices. There is a potential for use of polyelectrolytes as a platform technology for stabilization of proteins in the PLGA microspheres.
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