期刊
ACTA PHARMACOLOGICA SINICA
卷 29, 期 9, 页码 1094-1102出版社
NATURE PUBLISHING GROUP
DOI: 10.1111/j.1745-7254.2008.00829.x
关键词
camptothecin; solid lipid nanoparticle; nanostructured lipid carrier; lipid emulsion; drug delivery; melanoma
Aim: Camptothecin is an anticancer drug that acts against a broad spectrum of tumors. The clinical application of camptothecin is limited by its insolubility, instability, and toxicity problems. The aim of this study was to develop and characterize lipid nanoparticles with different lipid cores which can circumvent these problems. Methods: Lipid nanoparticles made of Precirol (solid lipid nanoparticles; SLN-P), Compritol (SLN-C), Precirol+squalene (nanostructured lipid carriers; NLC), and squalene (a lipid emulsion; LE) as the lipid core material were prepared. These systems were assessed and compared by evaluating the mean diameter, surface charge, molecular environment, camptothecin release, and cell viability against a melanoma. The safety and storage stability of these systems were also preliminarily examined. Results: The particle size ranged from 190 to 310 nm, with the NLC and LE showing the smallest and largest sizes, respectively. The in vitro drug release occurred in a sustained manner in decreasing order as follows: LE>NLC>SLN-P>SLN-C. It was found that varying the type of inner phase had profound effects on cell viability. The SLN-P generally showed higher cytotoxicity than the free control. The treatment of melanomas with the camptothecin-loaded SLN-C and NLC yielded cytotoxicity comparable to that of the free form. The percentage of erythrocyte hemolysis by all nanoparticles was <= 5%, suggesting a good tolerance to lipid nanoparticles. Conclusion: The results collectively suggest that the SLN-P may have the potential to serve as a delivery system for parenteral camptothecin administration because of the sustained drug release, strong cytotoxicity, limited hemolysis, and good storage stability.
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