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PEG-poly(amino acid) block copolymer micelles for tunable drug release.
MedLine Citation:
PMID:  20372992     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
PURPOSE: To achieve tunable pH-dependent drug release in tumor tissues.
METHODS: Poly(ethylene glycol)-poly(aspartic acid) [PEG-p(Asp)] containing 12 kDa PEG and pAsp (5, 15, and 35 repeating units) were prepared. Hydrazide linkers with spacers [glycine (Gly) and 4-aminobenzoate (Abz)] were introduced to PEG-p(Asp), followed by drug conjugation [doxorubicin (DOX)]. The block copolymer-drug conjugates were either reconstituted or dialyzed in aqueous solutions to prepare micelles. Drug release patterns were observed under sink conditions at pH 5.0 and 7.4, 37°C, for 48 h.
RESULTS: A collection of six block copolymers with different chain lengths and spacers was synthesized. Drug binding yields were 13-43.6%. The polymer-drug conjugates formed <50 nm polymer micelles irrespective of polymer compositions. Gly-introduced polymer micelles showed marginal change in particle size (40 ± 10 nm), while the size of Abz-micelles increased gradually from 10 to 40 nm as the polymer chain lengths increased. Drug release patterns of both Gly and Abz micelles were pH-dependent and tunable. The spacers appear to play a crucial role in controlling drug release and stability of polymer micelles in combination with block copolymer chain lengths.
CONCLUSION: A drug delivery platform for tunable drug release was successfully developed with polymer micelles possessing spacer-modified hydrazone drug-binding linkers.
Authors:
Andrei Ponta; Younsoo Bae
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-06
Journal Detail:
Title:  Pharmaceutical research     Volume:  27     ISSN:  1573-904X     ISO Abbreviation:  Pharm. Res.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2330-42     Citation Subset:  IM    
Affiliation:
Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone, Lexington, Kentucky 40536, USA.
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