Development and evaluation of lipid nanoparticles for camptothecin delivery: a comparison of solid lipid nanoparticles, nanostructured lipid carriers, and lipid emulsion.
OBJECTIVE
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 < or =5%, suggesting a good tolerance to lipid nanoparticles.


CONCLUSIONS
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.
Huang
Zih-rou
ZR
Pharmaceutics Laboratory, Chang Gung University, Taoyuan, Taiwan, China.
Hua
Shu-chiou
SC
Yang
Yueh-lung
YL
Fang
Jia-you
JY
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D002166:Camptothecin / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004355:Drug Stability; D004655:Emulsions; D004912:Erythrocytes / Q000187:drug effects; D005079:Excipients; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007267:Injections; D008055:Lipids / Q000737:chemistry; D053758:Nanoparticles; D010316:Particle Size
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D004655:Emulsions; D005079:Excipients; D008055:Lipids; D002166:Camptothecin