Document Detail


pH-responsive oligodeoxynucleotide (ODN)-poly(ethylene glycol) conjugate through acid-labile beta-thiopropionate linkage: preparation and polyion complex micelle formation.
MedLine Citation:
PMID:  12959615     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
An oligodeoxynucleotide (ODN) conjugated to poly(ethylene glycol) (PEG) through a pH-responsive ester linkage (PEG-ODN conjugate) was successfully synthesized by the Michael reaction of 3'-thiol-modified ODN with a heterobifunctional PEG bearing an acetal group at the alpha-end and an acrylate group at the omega-end (acetal-PEG-acrylate), aimed at the development of a novel ODN delivery system. The prepared PEG-ODN conjugate and linear-poy(ethyleneimine) (L-PEI) spontaneously associated to form a polyion complex (PIC) micelle whose diameter and polydispersity index micro(2)/Gamma(2)) were 102.5 nm and 0.096 as determined by DLS measurements, respectively. Both the PEG-ODN conjugate and PIC micelle showed cleavage of the ester linkage at the endosomal pH (=5.5), suggesting that the PIC micelle is anticipated to release the ODN in the intracellular compartment. Furthermore, the PEG-ODN conjugate in the PIC micelle was stable against deoxyribonuclase (DNase I) digestion and has no interaction with the serum component because of the steric stabilization of the highly dense PEG corona surrounding the PIC core. These characteristics of the PIC micelles entrapping the PEG-ODN conjugate are promising for their utility as a novel ODN delivery system.
Authors:
Motoi Oishi; Shigeki Sasaki; Yukio Nagasaki; Kazunori Kataoka
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biomacromolecules     Volume:  4     ISSN:  1525-7797     ISO Abbreviation:  Biomacromolecules     Publication Date:    2003 Sep-Oct
Date Detail:
Created Date:  2003-09-08     Completed Date:  2004-06-17     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100892849     Medline TA:  Biomacromolecules     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1426-32     Citation Subset:  IM    
Affiliation:
Department of Materials Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Proteins
Cattle
Deoxyribonucleases / metabolism
Drug Delivery Systems / methods*
Drug Stability
Hydrogen-Ion Concentration
Hydrolysis
Micelles*
Oligodeoxyribonucleotides / administration & dosage,  chemistry*
Polyethylene Glycols / chemistry*
Propionates
Chemical
Reg. No./Substance:
0/Blood Proteins; 0/Micelles; 0/Oligodeoxyribonucleotides; 0/Polyethylene Glycols; 0/Propionates; EC 3.1.-/Deoxyribonucleases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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