title: A stabilizer-free and organic solvent-free method to prepare 10-hydroxycamptothecin nanocrystals: in vitro and in vivo evaluation.
abstract: 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.
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Yang
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing; School of Pharmacy, Heilongjiang University of Traditional Chinese Medicine, Harbin, People's Republic of China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing.
authors.forename: Yanna
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing.
authors.forename: Meihua
authors.initials: M
authors.lastname: Han
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Guo
authors.affiliation: School of Pharmacy, Heilongjiang University of Traditional Chinese Medicine, Harbin, People's Republic of China.
authors.forename: Haixue
authors.initials: H
authors.lastname: Kuang
authors.affiliation: Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing.
authors.forename: Xiangtao
authors.initials: X
authors.lastname: Wang
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D065546:Drug Liberation; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D005612:Freeze Drying; D006801:Humans; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D036103:Nanotechnology / Q000379:methods*; D009930:Organic Chemicals / Q000737:chemistry*; D010316:Particle Size; D017207:Rats, Sprague-Dawley; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D014018:Tissue Distribution / Q000187:drug effects; D014961:X-Ray Diffraction
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D009930:Organic Chemicals; D012997:Solvents; C028098:10-hydroxycamptothecin; D002166:Camptothecin
keywords: 10-hydroxycamptothecin; 4T1 cells; drug delivery; high drug payload; poloxamer 188