Preparation, characterization, in vitro evaluation, cytotoxic and antitumor activity of rubitecan inlcusive liposomes with 2-hydoxy propyl--cyclodextrins as potential antitumor drug delivery system

Abstract

It is an oral topoisomerase inhibitor, having oral absorption of about 25-30% leading to low bioavailability of the drug due to low permeability and poor water solubility. The aim of the present study is to improve the solubility and dissolution rate and in turn the sufficient activity against pancreatic cancer of the drug, by formulating its inclusion complex with beta (β)-cyclodextrin, using different methods. The phase solubility analysis indicates the formation of 1:1 molar inclusion complex of the drug with beta cyclodextrin. Phase solubility analysis of Rubetican-HPβCD mixture provided k1:1 value of 1188 M-1. The prepared complexes were characterized using differential scanning calorimetry, scanning electron microscopy, and x-ray diffractometry. The results suggest that using “drug-in-CDinclusion complex in liposome” approach is a feasible strategy to formulate. These prepared liposomes by double-loading technique seem to be a suitable targeted drug delivery system because they have a fast onset action with prolonged drug release process and the significantly enhanced drug-loading capacity.