A stabilizer-free and organic solvent-free method to prepare 10-hydroxycamptothecin nanocrystals: in vitro and in vivo evaluation.
10-Hydroxycamptothecin (10-HCPT) is a promising anticancer drug with a wide spectrum of antitumor activities. Due to its poor solubility, the carboxylate form that shows high water solubility but minimal anticancer activity and pharmacokinetic defects is used in the marketed 10-HCPT injections, resulting in its limited clinical application. To develop a simple, safe, and highly effective drug delivery system, a modified acid-base microprecipitation combined with a high-pressure homogenization technique was adopted to prepare 10-HCPT nanocrystals. Neither organic solvents nor stabilizers were employed throughout the preparation process. The in vitro and in vivo performances of the resulting10-HCPT nanocrystals were investigated systematically. The nanocrystals were spherical with a small size of ~130 nm, and the actual drug-loading content was as high as 75%. The nanocrystals displayed a sustained release pattern and were proven to have a higher cell uptake and antiproliferative activity than the 10-HCPT injections. The 10-HCPT nanocrystals also showed enhanced drug accumulation in tumors and better anticancer efficacy in 4T1-bearing mice. In summary, the 10-HCPT nanocrystals prepared in this study seem to be a promising delivery system for a new form of 10-HCPT dosages.
['Yang|Xiaofeng|X|', 'Liu|Yingying|Y|', 'Zhao|Yanna|Y|', 'Han|Meihua|M|', 'Guo|Yifei|Y|', 'Kuang|Haixue|H|', 'Wang|Xiangtao|X|']
D061605:Administration, Intravenous D000818:Animals D000970:Antineoplastic Agents D000972:Antineoplastic Agents, Phytogenic D002166:Camptothecin D045744:Cell Line, Tumor D049109:Cell Proliferation D065546:Drug Liberation D004705:Endocytosis D005260:Female D005612:Freeze Drying D006801:Humans D008807:Mice, Inbred BALB C D053758:Nanoparticles D036103:Nanotechnology D009930:Organic Chemicals D010316:Particle Size D017207:Rats, Sprague-Dawley D012995:Solubility D012997:Solvents D014018:Tissue Distribution D014961:X-Ray Diffraction
10-hydroxycamptothecin drug delivery 4T1 cells high drug payload poloxamer 188