Development of a polycaprolactone modified release system for application of hemp seed oil containing cannabidiol with soft gelatin capsule

Cannabidiol (CBD) shows promise in the treatment of various diseases such as multiple sclerosis, Parkinson's disease, anorexia, glaucoma, cancer, pain, nausea and vomiting, depression, insomnia, and stress and anxiety disorders. However, CBD's high lipophilic properties make its administration and dosing challenging, thus limiting its pharmaceutical utility. The aim of this thesis study is to develop a suitable dosage form for the use of CBD in food supplements and to ensure its successful encapsulation. Nanoparticles (NPs) were synthesized using polycaprolactone (PCL) polymers with different molecular weights through ultrasonic homogenization and emulsification solvent evaporation method using an ultra-turrax. In optimization studies, the effects of different molecular weights and production methods on particle size and zeta potential were evaluated. The most suitable polymer was found to be PCL with a molecular weight of 14,000 g/mol, and PCL NPs encapsulated 5 mg, 10 mg, 15 mg, and 30 mg CBD were prepared using ultrasonication. The CBD-encapsulated NPs were characterized in terms of morphological and surface properties. Potential values of -23.37, -10.21, -9.62, -9.93, and -9.40 mV were determined for placebo NPs and 5 mg, 10 mg, 15 mg, and 30 mg CBD-encapsulated PCL NPs, respectively. The average sizes of placebo NPs and 5 mg, 10 mg, 15 mg, and 30 mg CBD-encapsulated PCL NPs were determined to be 207.5 nm, 227.2 nm, 225.5 nm, 227.7 nm, and 216.9 nm, respectively. In vitro release studies of CBD-PCL-NPs were conducted at two different pH values (1.2 and 7.4). The drug-polymer compatibility of NPs was revealed by DSC analysis. Additionally, FT-IR analysis results demonstrated the encapsulation of CBD into NPs. In silico analyses were performed using molecular docking method to investigate the interaction of CBD with various receptors. The structural behavior, affinity, and toxicity of this molecule on receptors were evaluated. The uptake of PCL-NPs into cells was demonstrated by the accumulation of Nile red-encapsulated NPs within the cells. The effect of püre CBD on cells was determined by cell viability analysis and calculation of IC50 values after 24, 48, and 72 hours of incubation with L929 normal fibroblast cells and MCF-7 breast cancer cells. The results indicate that CBD-PCL-NPs, in combination with hemp seed oil, may be developed as a food supplement in the form of soft gelatin capsules. A prototype production of soft gelatin capsules containing hemp seed oil was carried out and packaged for use as a food supplement. The capsules are capable of long-term CBD release and offer pharmaceutical advantages compared to free CBD consumption.