Pharmacokinetic analysis and optimization of hydroxycamptothecin-loaded nanoparticles for liver targeting

Abstract

In this paper, a pharmacokinetic model to describe the tissue distribution process of nanoparticles was established. To test the possibility of the model, nanoparticles composed of poly(butylcyanoacrylate) and hydroxypropyl-β-cyclodextrins (HP-β-CD) was prepared with a poorly soluble anticancer drug, hydroxycamptothecin (HCPT). Characteristics were determined including particle’s size, morphology and in vitro release. The tissue distribution of nanoparticles was also studied. Further, mathematical equation was fitted to the curve of drug concentration-time in liver of hydroxycamptothecin-loaded nanoparticles and the pharmacokinetic parameters of liver were obtained. The effectiveness of hydroxycamptothecin-loaded nanoparticles for liver targeting was evaluated. The results showed that nanoparticles composed of poly(butylcyanoacrylate) and hydroxypropyl-β-cyclodextrins (HP-β-CD) exhibited enhanced liver targeting in rats after i.v. injection. More importantly, the pharmacokinetic parameters (transport constant from blood to target organ KT, drug release rate from nanoparticles Kr and drug elimination constant in target organ Ke) provided some quantitative measure of liver distribution and were useful guidelines for development of targeted drug delivery systems.

Keywords::

• Pharmacokinetic model
• nanoparticles
• liver targeting
• poly(butylcyanoacrylate)
• hydroxypropyl-β-cyclodextrins

Acknowledgments

The authors wish to thank Xingguo Yang and Jinli Wang for their help in these experiments.

Declaration of interest

This work was supported by natural science funds from administration of science and technology of Shandong province, China (Y2005C65). This paper has not been published elsewhere and it has not been submitted simultaneously for publication elsewhere. All authors have read and approved to submit it to your journal.