title: High Drug Payload 10-Hydroxycamptothecin Nanosuspensions Stabilized by Cholesterol-PEG: In Vitro and In Vivo Investigation.
abstract: The objective of this study was to evaluate the feasibility of producing 10-hydroxycamptothecin nanosuspensions with high drug payload and to then determine the in vitro and in vivo characteristics of these nanosuspensions. Using cholesterol-PEG600 as a stabilizer, 10-hydroxycamptothecin nanosuspensions were successfully prepared using a precipitation-combined high-pressure homogenization method. A satisfactory drug payload of 90.39% (w/w) was achieved. The obtained nanosuspensions were spherical, with a mean particle size of 115.0 ± 0.4 nm, and they were monodisperse with a polydispersity index of 0.134 ± 0.001. The 10-hydroxycamptothecin remained in the same crystalline form in both the nanosuspensions and the bulk powder. In vitro, the 10-hydroxycamptothecin nanosuspensions released the encapsulated drug with nearly zero-order kinetics, and the accumulative release reached 90% within 72 hours. In vitro cytotoxicity assay showed that the 1 0-hydroxycamptothecin nanosuspensions had significantly enhanced cytotoxicity against HepG2 cells compared to the commercially available 10-hydroxycamptothecin injections. The in vivo study with H22 tumor-bearing mice and intravenous injection of the drug showed that in contrast to the 10-hydroxycamptothecin injections, the 10-hydroxycamptothecin nanosuspensions exhibited significantly enhanced biodistribution, particularly in the lung (393.40-fold AUC(0-24h)), liver (192.35-fold AUC(0-24h)), spleen (141.67-fold AUC(0-24h)) and tumor (64.21-fold AUC(0-24h)). The 10-hydroxycamptothecin nanosuspensions also showed improved antitumor therapeutic efficacy over the injections (89.83% vs. 30.56%). This suggests that cholesterol-PEG600 may be an effective stabilizer for the preparation of hydrophobic drug nanosuspensions and that 10-hydroxycamptothecin nanosuspensions are a promising drug delivery system for tumor treatment.
authors: Linjie
authors: L
authors: Yang
authors: Jizong
authors: J
authors: Jiang
authors: Jingyi
authors: J
authors: Hong
authors: Jing
authors: J
authors: Di
authors: Yonghong
authors: Y
authors: Liao
authors: Haixue
authors: H
authors: Kuang
authors: Xiangtao
authors: X
authors: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D019540:Area Under Curve; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002784:Cholesterol / Q000737:chemistry*; D003460:Crystallization; D016503:Drug Delivery Systems; D056945:Hep G2 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry; D009368:Neoplasm Transplantation; D011092:Polyethylene Glycols / Q000737:chemistry*; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D014961:X-Ray Diffraction
chemical_list: D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; D002784:Cholesterol; C028098:10-hydroxycamptothecin; D002166:Camptothecin