High Drug Payload 10-Hydroxycamptothecin Nanosuspensions Stabilized by Cholesterol-PEG: In Vitro and In Vivo Investigation

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 10-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(0-24 h)), liver (192.35-fold AUC(0-24 h)), spleen (141.67-fold AUC(0-24 h)) and tumor (64.21-fold AUC(0-24 h)). 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.