Document Detail


Physicochemical properties and nuclease resistance of antisense-oligodeoxynucleotides entrapped in the core of polyion complex micelles composed of poly(ethylene glycol)-poly(L-lysine) block copolymers.
MedLine Citation:
PMID:  11292566     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In this study, the physicochemical properties of polyion complex (PIC) micelles formed from antisense-oligodeoxynucleotides (antisense-ODN) and poly(ethylene glycol)-poly(L-lysine) block copolymers (PEG-PLL) were investigated to utilize them as a novel formulation for antisense-ODN delivery. Angular and concentration dependences of the diffusion coefficient of PIC micelles were evaluated by dynamic light scattering. Results suggested that the formed PIC micelles may have spherical shape with core-shell structure, in which the PIC core formed from antisense-ODN and PLL segment was surrounded by a PEG shell. The average radius of PIC micelles was dependent on the chain length of the PLL segment and was not influenced by the change in the length of ODN molecules at least in the range between 15 and 20 base pairs. Critical association concentration (cac) of PIC micelles was then determined from a profile of light scattering intensity versus concentration (Debye plots). Cac is ca. 0.20 mg/ml, which is low enough to ensure the micelle stability in very diluted condition as is the case with systemic injection into the blood compartment for antisense-ODN therapy. Furthermore, the stability of antisense-ODN against deoxyribonuclease I (DNase I) attack was evaluated using capillary gel electrophoresis, revealing that the complexation of antisense-ODN with PEG-PLL effectively prohibited DNase I attack. These characteristics of the PIC micelle system highlight its promising feature as ODN carrier used in the field of targeting therapy.
Authors:
A Harada; H Togawa; K Kataoka
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences     Volume:  13     ISSN:  0928-0987     ISO Abbreviation:  Eur J Pharm Sci     Publication Date:  2001 Apr 
Date Detail:
Created Date:  2001-04-09     Completed Date:  2001-08-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9317982     Medline TA:  Eur J Pharm Sci     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  35-42     Citation Subset:  IM    
Affiliation:
Department of Materials Science, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-8656, Tokyo, Japan.
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MeSH Terms
Descriptor/Qualifier:
Deoxyribonuclease I / pharmacology
Micelles*
Oligonucleotides, Antisense / chemistry*,  drug effects
Polyethylene Glycols / chemistry*
Polylysine / chemistry*,  drug effects
Chemical
Reg. No./Substance:
0/(O-methylpoly(ethylene glycol)-O'-succinyl)-N-epsilon-poly(L-lysine); 0/Micelles; 0/Oligonucleotides, Antisense; 0/Polyethylene Glycols; 25104-18-1/Polylysine; EC 3.1.21.1/Deoxyribonuclease I

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