Body distribution of camptothecin solid lipid nanoparticles after oral administration

• Published in: Pharmaceutical research 1999-05, Vol.16 (5), p.751-757
• Main Authors: Yang, S, Zhu, J, Lu, Y, Liang, B, Yang, C
• Format: Article
• Language: English
• Subjects: Acids; Administration, Oral; Animals; Antineoplastic agents; Antineoplastic Agents, Phytogenic - blood; Antineoplastic Agents, Phytogenic - pharmacokinetics; Biological activity; Biological and medical sciences; Blood-Brain Barrier; Camptothecin - blood; Camptothecin - pharmacokinetics; Cellulose acetate; Chromatography; Chromatography, High Pressure Liquid; Delayed-Action Preparations; Drugs; General aspects; General pharmacology; Glycerol; Lipids; Medical sciences; Mice; Mice, Inbred C57BL; Nanoparticles; Oils & fats; Oral administration; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Physiology; Soybeans; Tissue Distribution; Toxicity; Transmission electron microscopy
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1023/A:1018888927852

The aim of this study was to investigate the specific changes in body distribution of camptothecin (CA) through incorporation into solid lipid nanoparticles (SLN) by peroral route. Camptothecin loaded solid lipid nanoparticles (CA-SLN) coated with poloxamer 188 were produced by high pressure homogenization. The CA-SLN were characterized by transmission electron microscopy and electrophoretic mobility measurement. In vitro release characteristics of camptothecin from CA-SLN were studied at different pH media. The concentration of camptothecin in organs was determined using reversed-phase high-performance liquid chromatography with a fluorescence detector after oral administration of CA-SLN and a camptothecin control solution (CA-SOL). Our results showed that CA-SLN had an average diameter 196.8 nm with Zeta potential of -69.3 mV. The encapsulation efficiency of camptothecin was 99.6%, and in vitro drug release was achieved up to a week. There were two peaks in the camptothecin concentration-time curves in plasma and tested organs after oral administration of CA-SLN. The first peak was the result of free drug and the second peak was indicative of gut uptake of CA-SLN after 3 hours. In tested organs, the area under curve (AUC) and mean residence time (MRT) of CA-SLN increased significantly as compared with CA-SOL, and the increase of brain AUC was the highest among all tested organs. The results indicate SLN could be a promising sustained release and targeting system for camptothecin or other lipophilic antitumor drugs after oral administration.