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 Yang, Jizong Jiang, Jingyi Hong, Jing Di, Yonghong Liao, Haixue Kuang, Xiangtao Wang
• Journal: Journal of biomedical nanotechnology (J Biomed Nanotechnol) Vol. 11 Issue 4 Pg. 711-21 (Apr 2015) ISSN: 1550-7033 [Print] United States
• PMID: 26310077 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Polyethylene Glycols
• Cholesterol
• 10-hydroxycamptothecin
• Camptothecin

Topics

• Animals
• Antineoplastic Agents (administration & dosage)
• Area Under Curve
• Camptothecin (administration & dosage, analogs & derivatives)
• Cholesterol (chemistry)
• Crystallization
• Drug Delivery Systems
• Hep G2 Cells
• Humans
• Male
• Mice
• Mice, Inbred ICR
• Microscopy, Electron, Scanning
• Microscopy, Electron, Transmission
• Nanomedicine (methods)
• Nanoparticles (chemistry)
• Neoplasm Transplantation
• Polyethylene Glycols (chemistry)
• Pressure
• Rats
• Rats, Sprague-Dawley
• X-Ray Diffraction