Development and evaluation of solid lipid nanoparticles for enhanced peroral bioavailability of capecitabine

This work aimed to improve the peroral bioavailability of capecitabine (CPB) by developing and assessing solid lipid nanoparticles (SLNs). SLNs were made using the modified nanoprecipitation method. Particle size, zeta potential, entrapment efficiency, drug loading, <i>in-vitro</i> drug release, TEM, <i>in-vivo</i> pharmacokinetic study, stability study, histopathological evaluation and cytotoxicity study were assessed. The TEM revealed that the SLNs were transparent, with a mean particle size ranging from 13.06 ± 0.09 to 86.10 ± 0.15 nm. The F-3 formulation demonstrated the highest drug entrapment efficiency at 45.49 ± 0.28. The zeta potential and polydispersity index of all SLNs ranged from -15.53 ± 0.17 to 17.55 ± 0.18 mV and from 0.1356 ± 0.11 to 0.2678 ± 0.13, respectively. The drug entrapment efficiency and drug loading of all SLNs ranged from 18.45 ± 0.36 to 45.49 ± 0.28 and from 21.75 ± 0.64 to 59.49 ± 0.38, respectively. The CPB-SLNs showed sustained drug release with prolonged plasma retention, delayed Tmax, and extended half-life compared to raw CPB. <i>In vivo</i> pharmacokinetic studies suggest that developed SLNs may enhance therapeutic efficacy by maintaining drug concentrations in plasma for longer periods. Toxicity was observed at 200 mg/kg/day, indicated by changes in clinical biochemistry, organ weights, and histopathology, particularly affecting the liver and kidneys. Therefore, it can be said that these developed SLNs may be among the best preparations for the delivery of anti-cancer drugs for improved therapeutic efficacy.