Self-assembled lecithin-chitosan nanoparticles improve the oral bioavailability and alter the pharmacokinetics of raloxifene.

In this study, we report the development and evaluation of soy lecithin-chitosan hybrid nanoparticles to improve the oral bioavailability of raloxifene hydrochloride. The nanoparticles were formed by interaction of negatively charged soy lecithin with positively charged chitosan. The ratio of soy lecithin to chitosan was critical for the charge, and hence the size of the nanoparticles. The optimal soy lecithin to chitosan ratio was 20:1 to obtain nanoparticles with particle size of 208 ± 3 nm, a ζ-potential of 36 ± 2 mV and an entrapment efficiency of 73 ± 3%. The nanoparticles were also characterized by differential scanning calorimetry and FT-IR spectrophotometer. In-vitro drug release was assessed using dialysis bag method in pH 7.4 buffer. The drug loaded nanoparticles did not cause significant reduction in the cell viability at low doses. Pharmacokinetic studies in female Wistar rats showed significant improvement (~4.2 folds) in the oral bioavailability of the drug when loaded into nanoparticles. Further, the modified everted gut sac study showed that these nanoparticles are taken up by active endocytic processes in the intestine. The ex-vivo mucoadhesion studies proved that the nanoparticles get bound to the mucus layer of the intestine, which in turn correlates with reduced excretion of the drug in faeces. In conclusion, the proposed nanoparticles appear promising for effective oral delivery of poorly bioavailable drugs like raloxifene hydrochloride.