No abstract

Objective: High lipophilicity and extensive hepatic metabolism limit oral application of orlistat in obesity treatment. Orlistat-loaded chitosan nanoparticles (CONPs) were optimized by 3-factor 3-level Box–Behnken design (BBD) and surfaced engineered to address limitations. Methods: CONPs were prepared by ionic gelation method. Amounts of chitosan (X1), sodium tripoly phosphate (X2), and orlistat (X3) were selected as independent factors, whereas % entrapment efficiency (Y1) and % drug release (Y2) were employed as responses in BBD. Three-dimensional response surface plots were run to understand the main interaction and quadratic effects of independent variables. Further optimized formulation was surface engineered by Eudragit L-100 (ECONPs) and characterized by FTIR, DSC, XRD, particle size, zeta potential, and SEM. Entrapment efficiency, release kinetics, stability, and in vitro cell line studies were carried out. Results: ECONPs were produced with an average size of 534.6 nm, zeta potential of +5.7 mV, EE of 78.62%, and DR of 80.86%. Eudragit coated CONPs anchored the release of orlistat at pH 6.8 desirable for duodenal targeting. Orlistat was released with low, burst, and sustained release manner over 24 h period followed first-order kinetics with Higuchi model with drug content of 84.87% and 78.44% of release. ECONPs possessed lipase inhibition with IC50 value of 8.0 μg/ml and viability against selected cell lines with CTC50 values (26.32–32.21 μg/ml). Conclusion: BBD was a promising tool in elucidating the insights of formulation variables of CONPs. ECONPs fulfilled the rationale of orlistat release, lipase inhibition, and viability against selected cell lines.