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Evaluation of cationic solid lipid microparticles as synthetic carriers for the targeted delivery of macromolecules to phagocytic antigen-presenting cells

Paper ID Volume ID Publish Year Pages File Format Full-Text
13101 829 2002 10 PDF Available
Title
Evaluation of cationic solid lipid microparticles as synthetic carriers for the targeted delivery of macromolecules to phagocytic antigen-presenting cells
Abstract

Biodegradable microparticles represent a promising carrier system for the efficient delivery of therapeutic macromolecules to phagocytic professional antigen-presenting cells (APC). Solid lipid microparticles (SLM) consisting of a tripalmitin matrix were prepared using a novel micromixer-based solvent extraction process. A positive surface charge was introduced by the incorporation of cationic lipids into the formulation. All obtained SLM were efficiently phagocytosed by primary macrophages in vitro. Complete intracellular degradation was observed already within 24 h, making SLM a suitable carrier for the immediate delivery of therapeutics to APC. Cationic SLM adsorbed plasmid DNA and bovine serum albumin (BSA) used as a model protein, and triggered the cellular internalization of the macromolecules by phagocytic macrophages. Surprisingly, the cationic SLM also triggered the internalization of these molecules by non-phagocytic 293 cells. This was probably due to the detachment of nanocomplexes formed of cationic lipid and DNA or BSA, respectively, from the surface of DNA- or BSA-loaded SLM and their subsequent uptake into the cells. Transfection efficiency of the DNA-loaded SLM was most pronounced in non-phagocytic cells and was not detected in the macrophage cell line or in primary macrophages. Our further studies revealed that cytotoxic effects of cationic SLM were more pronounced in the phagocytic cells, which could be explained by the very rapid uptake and degradation of the cationic SLM in these cells. In conclusion, SLM may provide a new, efficient means for the immediate intracellular delivery of therapeutic macromolecules into APC. Caution is warranted for cationic carriers, which may accentuate cytotoxic effects in the phagocytic cells.

Keywords
Solid lipid microparticles; Phagocytosis; Macrophages; DNA; Transfection efficiency; Cationic lipid; Toxicity
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Evaluation of cationic solid lipid microparticles as synthetic carriers for the targeted delivery of macromolecules to phagocytic antigen-presenting cells
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 23, Issue 23, December 2002, Pages 4667–4676
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us