Novel colon-specific microspheres with highly dispersed hydroxycamptothecin cores: their preparation, release behavior, and therapeutic efficiency against colonic cancer.
To increase therapeutic efficiency of hydroxycamptothecin (HCPT) against colonic cancer and decrease its side-effects, highly dispersed HCPT was first incorporated in fast release microspheres. HCPT in the microspheres showed a solubility two times larger, and its cumulative release rate for 24 h in simulated colonic juice 140 times higher than that of free HCPT. The microspheres were then coated with a layer of Eudragit S100 by air suspension spray-drying method with a self-designed device to obtain colon-specific microspheres (HCPT-CSMS). The mean particle size of the microspheres was 200 microm before coating and 230 microm after coating. The in vitro cumulative release results for HCPT-CSMS in simulated gastric juice for 2 h, in simulated enteric juice for 4 h, and in simulated colonic juice for 18 h showed that over 60% of total HCPT released in simulated colonic juice in the initial 5 h. Animal tests with per os (po) administration showed that free HCPT was mainly absorbed in stomach and small intestine, while the HCPT in HCPT-CSMS was mainly delivered and absorbed in colon. po administration of HCPT-CSMS to nude mice with colonic cancer showed a cancer inhibition rate of 61.4% compared to 39.8% for free HCPT.
Lu
Bin
B
West China School of Pharmacy, Sichuan University, China. lubin@wcums.edu.cn
Zhang
Zhengquan
Z
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002166:Camptothecin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005260:Female; D005750:Gastric Juice / Q000737:chemistry; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D007419:Intestinal Secretions / Q000737:chemistry; D007421:Intestine, Small / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008863:Microspheres; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D002166:Camptothecin