DESIGN AND CHARACTERIZATION OF PACLITAXEL LOADED NANOPARTICLES WITH PIPERINE

Abstract

Objectives: Paclitaxel is a cytotoxic drug having wonderful mechanism against cancer cells. However, it showed severe dose-limiting toxicity when administered as infusion. To overcome these side effects a suitable delivery system is highly desirable. Bioenhancers, when mixed with drugs promote and augment their bioavailability and reduced incidence of drug resistance and risk of adverse drug reaction. Therefore, we selected nanoparticles as a delivery system in this study. The object of this work was to entrap paclitaxel and herbal bioenhancer in a nanoparticle system. Materials and methods: We prepared the nanoparticles by emulsion solvent evaporation method with Eudragit RLPO polymer. The prepared nanoparticles were evaluated for particle size, zeta potential, drug entrapment, in vitro drug release. Further the nanoparticles were evaluated for in vitro cell cytotoxicity study by MTT assay on lung cancer cell line and pharmacokinetic profile. Results: The revealed good in vitro properties with 124-200 nm particle size range. All the formulations released within the range of 82.71to 95.47 % of drug in 24 h. The release kinetic of drug was best fitted to Higuchi’s model and was following Fick’s law of diffusion. All the nanoparticle batches had good drug entrapment capacity in the range of 57.51 % to 86.12%. The pure drug solution could not inhibit the cell proliferation completely but the nanoparticle formulations significantly reduced the cell proliferation in MTT assay. Surprisingly, formulation with higher bioenhancer loading (FNP 6) showed a higher antiproliferative effect on A549 cells. In in vivo pharmacokinetic assay, the plasma level of FNP-6 was highest than other formulation including control. (As shown in graphical abstract) Conclusion: The AUC of FNP-6 was 6.423µg/ml and the absolute bioavailability of FNP-6 was 7.89. FNP-5 and FNP-6 had a higher bioenhancer quantity as compare to the other formulation this may be possible reason of their higher absolute bioavailability. Therefore, it can be concluded that addition of bioenhancer with antitumor drug can enhance its prolifertive effect and bioavailability.