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

Area of Science:

• Materials Science
• Nanotechnology
• Pharmacology

Background:

• Cannabidiol (CBD) demonstrates anticancer properties.
• Biocompatible polymers like Polyhydroxybutyrate (PHB) and cellulose acetate phthalate (CAP) can enhance drug delivery.
• pH-responsive drug delivery systems are crucial for targeted therapies.

Purpose of the Study:

• To optimize the fabrication of pH-responsive cannabidiol (CBD)-loaded PHB/CAP microparticles.
• To evaluate the physicochemical properties, stability, and in vitro anticancer efficacy of the optimized microparticles.
• To assess the potential of these microparticles for anticolorectal cancer applications.

Main Methods:

• Response Surface Methodology (RSM) with a Box-Behnken design was employed for optimization.
• Fabrication of CBD-loaded PHB/CAP microparticles.
• Characterization of microparticle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, and loading capacity.
• In vitro release studies at different pH values and stability testing.
• In vitro cytotoxicity assays on Caco-2 cells to determine half-maximal inhibitory concentration (IC50).

Main Results:

• The optimized formulation (7% PHB/CAP, 3:1 ratio, 7.33% CBD) yielded high encapsulation efficiency (71.8%) and loading capacity (53.4%).
• Microparticles exhibited suitable characteristics for intestinal delivery (size ~211 μm, PDI ~0.98, zeta potential ~-36 mV) and good stability.
• pH-responsive CBD release was observed, with sustained release over 6 hours and stability for 90 days.
• Significant dose-dependent inhibition of Caco-2 cell proliferation was demonstrated, with IC50 values of 129.0 μg/mL at 24h and 144.2 μg/mL at 48h.

Conclusions:

• Optimized pH-responsive CBD-loaded PHB/CAP microparticles offer a promising drug delivery strategy.
• The formulation demonstrates good physicochemical properties, stability, and potent in vitro anticancer activity against colorectal cancer cells.
• These microparticles hold significant potential for the development of novel anticolorectal cancer therapeutics.