Preparation, in vitro and in vivo evaluation of bexarotene nanocrystals with surface modification by folate-chitosan conjugates

Abstract

Bexarotene (Bex) is a synthetic retinoid that exhibits anti-tumor activities. However, the low solubility of the compound hinders its development. In this study, bexarotene nanocrystal was developed and its surface was modified to improve the dissolution and absorption of the drug. The nanocrystals were prepared via precipitation, high-pressure homogenization method, and modified by folate-chitosan (FA-CS), which relied on the charge interaction between the negatively charged nanocrystals and the positively charged FA-CS. The physical–chemical properties in terms of particle size, size distribution, zeta potential, morphology and crystallinity were evaluated. The results showed that bexarotene nanocrystals with surface modification by folate–chitosan conjugates (FC–NC–Bex) with a mean particle size of 631.3 ± 2.7 nm, a polydispersity index of 0.33 ± 0.06 and a zeta potential of 24.6 ± 1.9 mV was obtained. The result of differential scanning calorimetry (DSC) showed that the nanocrystals were still in crystalline state after the preparation procedure. In the in vitro dissolution test, FC-NC-Bex showed significant increase in dissolution rate compared to raw bexarotene (nearly 6.5-fold). Compared to bexarotene suspension, FC-NC-Bex exhibited significant increase in AUC_0–∞ (approximately 3-fold) and C_max (about 1.5-fold). Taken together, the results suggested that FC-NC-Bex may provide a potential opportunity in enhancing the dissolution rate of bexarotene and its gastrointestinal absorption.

• Bexarotene
• chitosan
• folate
• nanocrystals
• surface modified

Acknowledgements

The authors gratefully acknowledge the support provided by Department of Pharmaceutics, School of Pharmaceutical Sciences, Shandong University, China. We would like to thank Shenyang Pharmaceutical University, China for their support in animal experiments and bexarotene synthesis study. We also thank Dr. Alan K. Chang for helpful discussion and for revising the language of the manuscript.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This work was supported by the Liaoning Provincial Science and Technology Program of China, No. 2013305003.