Optimization of pH-responsive cannabidiol-loaded polyhydroxybutyrate/cellulose acetate phthalate microparticles using...

Cannabidiol (CBD) is a promising anticancer agent, and its delivery can be enhanced using biocompatible polymers. Polyhydroxybutyrate (PHB) and cellulose acetate phthalate (CAP) are non-toxic polymers suitable for drug encapsulation. This study optimized the fabrication of pH-responsive CBD-loaded PHB/CAP microparticles using response surface methodology (RSM) with a Box-Behnken design. The effects of polymer concentration, PHB:CAP ratio, and initial CBD concentration were evaluated. The optimized formulation, 7 % (w/v) PHB and CAP polymer, a 3:1 PHB:CAP ratio, and 7.33 % (w/v) CBD, achieved an encapsulation efficiency of 71.8 ± 3.1 % and a loading capacity of 53.4 ± 3.8 %. The microparticles were spherical with an average size of 211.1 ± 0.6 μm, a polydispersity index (PDI) of 0.98 ± 0.01, and a zeta potential of -35.93 ± 1.43 mV, indicating good stability and suitability for intestinal delivery. The formulation exhibited pH-responsive CBD release over 6 h and maintained over 80 % of CBD content after 90 days at 4 °C. In vitro studies showed dose-dependent inhibition of Caco-2 cell proliferation, with the half-maximal inhibitory concentration (IC₅₀) values of 129.0 μg/mL at 24 h and 144.2 μg/mL at 48 h. These findings highlight the potential of pH-responsive CBD-loaded PHB/CAP microparticles for anticolorectal cancer activity.