Document Detail


Poly(alkylene oxide) copolymers for nucleic acid delivery.
MedLine Citation:
PMID:  22260518     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The advancement of gene-based therapeutics to the clinic is limited by the ability to deliver physiologically relevant doses of nucleic acids to target tissues safely and effectively. Over the last couple of decades, researchers have successfully employed polymer and lipid based nanoassemblies to deliver nucleic acids for the treatment of a variety of diseases. Results of phase I/II clinical studies to evaluate the efficacy and biosafety of these gene delivery vehicles have been encouraging, which has promoted the design of more efficient and biocompatible systems. Research has focused on designing carriers to achieve biocompatibility, stability in the circulatory system, biodistribution to target the disease site, and intracellular delivery, all of which enhance the resulting therapeutic effect. The family of poly(alkylene oxide) (PAO) polymers includes random, block, and branched structures, among which the ABA type triblocks copolymers of ethylene oxide (EO) and propylene oxide (PO) (commercially known as Pluronic) have received the greatest consideration. In this Account, we highlight examples of polycation-PAO conjugates, liposome-PAO formulations, and PAO micelles for nucleic acid delivery. Among the various polymer design considerations, which include molecular weight of polymer, molecular weight of blocks, and length of blocks, the overall hydrophobic-lipophilic balance (HLB) is a critical parameter in defining the behavior of the polymer conjugates for gene delivery. We discuss the effects of varying this parameter in the context of improving gene delivery processes, such as serum stability and association with cell membranes. Other innovative macromolecular modifications discussed in this category include our work to enhance the serum stability and efficiency of lipoplexes using PAO graft copolymers, the development of a PAO gel-based carrier for sustained and stimuli responsive delivery, and the development of biodegradable PAO-based amphiphilic block copolymers.
Authors:
Swati Mishra; Lavanya Y Peddada; David I Devore; Charles M Roth
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-01-19
Journal Detail:
Title:  Accounts of chemical research     Volume:  45     ISSN:  1520-4898     ISO Abbreviation:  Acc. Chem. Res.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-17     Completed Date:  2012-11-09     Revised Date:  2014-09-15    
Medline Journal Info:
Nlm Unique ID:  0157313     Medline TA:  Acc Chem Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1057-66     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
COS Cells
Cercopithecus aethiops
Liposomes / chemistry
Mice
Micelles
NIH 3T3 Cells
Nucleic Acids / genetics,  metabolism*
Poloxamer / chemistry
Polyethylene Glycols / chemistry
Polymers / chemistry*
Transfection
Grant Support
ID/Acronym/Agency:
EB 008278-07/EB/NIBIB NIH HHS; R01 EB008278/EB/NIBIB NIH HHS; R01 EB008278-07/EB/NIBIB NIH HHS
Chemical
Reg. No./Substance:
0/Liposomes; 0/Micelles; 0/Nucleic Acids; 0/Polyethylene Glycols; 0/Polymers; 106392-12-5/Poloxamer
Comments/Corrections

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