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Lipid Encapsulation of Cationic Polymers in Hybrid Nanocarriers Reduces Their Non-Specific Toxicity to Breast Epithelial Cells.
MedLine Citation:
PMID:  23135818     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
PURPOSE: Clinical application of cationic polymers for delivery of nucleic acids has been limited by their toxicity. The purpose of this study is to evaluate whether the polymer-in-lipid hybrid nanotechnology recently developed for controlled siRNA delivery can tackle this toxicity issue by reducing exposure of the cellular components to free cationic polymers. METHODS: Lipid-polymer hybrid nanocarriers (LPNs) encapsulating complexes of hexadecylated polyethylenimine (H-PEI) and biologically inactive siRNA in lipids were prepared at different lipid-polymer ratios. Comparative toxicity of these LPNs and unencapsulated cationic materials on breast epithelial cell lines MDA-MB-231 and MCF-10a was evaluated. RESULTS: Even at a low lipid-polymer ratio (3:1 w/w), encapsulation of H-PEI improved its LC(50) values measured within hours by 3-5 fold, and caused less reduction in the colony-formation rates in 10-14 days. The observed reductions in the acute and delayed carrier toxicity were associated with significantly less membrane damages, improved mitochondrial functions, reduced reactive oxidative species production, and lower caspase-3 activity (all p < 0.05) without sacrificing the siRNA transfection efficiency. CONCLUSIONS: This study has validated the hybrid nanotechnology for controlled RNA delivery from a toxicological perspective. This is especially valuable if local or long-term RNA therapy is intended for which low carrier toxicity is essential.
Authors:
Hui Yi Xue; Mayuri Narvikar; Juan-Bao Zhao; Ho Lun Wong
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-8
Journal Detail:
Title:  Pharmaceutical research     Volume:  -     ISSN:  1573-904X     ISO Abbreviation:  Pharm. Res.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 North Broad Street, Philadelphia, Pennsylvania, 19140, USA.
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