Nanoparticle-Based Oral Delivery of Capecitabine: In Vitro Cytotoxicity and Pharmacokinetic Evaluation in HepG2 and HT-29 Cell Lines

Present study aims to develop and assess a capecitabine-loaded nanoparticle formulation (C18) for improved oral bioavailability and targeted anticancer activity.Capecitabine nanoparticles were successfully prepared using a double emulsion solvent evaporation process. These nanoparticles were then tested for in vitro cytotoxicity using MTT assays against HT-29, HepG2 and L929 cell lines to calculate IC50 values. The pharmacokinetic properties of the medication and its nanoparticle formulation were also investigated in Wistar rats after oral administration. Validated HPLC methods were used to assess the plasma concentrations of 5-FU and capecitabine, and data was processed using PkSolver software.The nanoparticle formulation (C18) exhibited dose-dependent cytotoxicity by IC50 values of 38.91 µg/mL (HepG2) and 55.15 µg/mL (HT-29), showing superior anticancer activity compared to 5-FU. Cytotoxicity toward normal L929 cells was moderate, indicating selective toxicity. Pharmacokinetic studies revealed enhanced oral bioavailability, increased Cmax and AUC, and prolonged circulation time for the nanoparticle formulation compared to the conventional drug.Capecitabine-loaded nanoparticles demonstrated improved cytotoxic potential against cancer cell lines and favorable pharmacokinetic profiles, associate their probability as an active oral nanocarrier system for cancer therapy.