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The importance of endo-lysosomal escape with lipid nanocapsules for drug subcellular bioavailability.
MedLine Citation:
PMID:  20630585     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
To establish the therapeutic relevance of new nanocarriers, rationalization of knowledge on their interactions with biological structures is essential. In the present study, we have investigated endocytosis and intracellular trafficking of lipid nanocapsules (LNCs) in rat glioma cells. Radiolabelled and fluorescent LNCs were synthesized by using a phase inversion process that follows the formation of an oil/water microemulsion containing triglycerides, lecithins and a non-ionic surfactant, the hydroxystearate of poly(ethylene glycol) (HS-PEG). Our data revealed that LNCs were rapidly accumulated within cells (from 2 min exposure) through active and saturating mechanisms involving endogenous cholesterol with a major contribution of clathrin/caveolae-independent pathways. Although initially present in endosomes, LNCs can bypass the endo-lysosomal compartment with only 10% of the cell-internalized fraction found in isolated lysosomes after 2 h exposure. As demonstrated by use of lysosomal probes, LNCs reverted lysosome integrity similarly to V-ATPase inhibitors and in a size-dependent fashion with best efficiency for small nanoparticles. When loaded with paclitaxel, smallest LNCs also triggered the best cell death activity. Those LNC properties are ascribed to the proportion of HS-PEG they provided to the cell. They are important to consider toward the development of nanomedicines that use drugs sensitive to lysosomal degradation or that need to reach extra endo-lysosomal targets.
Authors:
Archibald Paillard; François Hindré; Caroline Vignes-Colombeix; Jean-Pierre Benoit; Emmanuel Garcion
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-14
Journal Detail:
Title:  Biomaterials     Volume:  31     ISSN:  1878-5905     ISO Abbreviation:  Biomaterials     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-08-03     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8100316     Medline TA:  Biomaterials     Country:  England    
Other Details:
Languages:  eng     Pagination:  7542-54     Citation Subset:  IM    
Copyright Information:
2010 Elsevier Ltd. All rights reserved.
Affiliation:
Laboratoire d'Ingénierie de la Vectorisation Particulaire, Inserm, UMR_S 646, Université d'Angers, Angers, France.
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