Nanocarreadores lipídicos aplicados à molécula canabidiol

Abstract

Cannabidiol (CBD) is one of the special metabolites present in Cannabis sativa that does not cause the typical hallucinogenic effects shown by Delta-9-Tetrahydrocannabinol (∆9- THC); however, it has several pharmacological effects with applications of therapeutic interest. Although CBD has promising clinical potential, with emphasis on its use in certain psychiatric and neurological disorders, this molecule has limitations due to its very low bioavailability, high lipophilicity, instability in gastric pH and susceptibility to first-pass metabolism. Such characteristics limit the development of a formulation for its administration by a widely used, safe, economical, and comfortable route, such as the oral route. In this context, this work aims to develop a microemulsion system for CBD oral delivery with theoretical basis in a literature review. All scientific studies related to the development of advanced drug delivery systems containing CBD that were published up to January 2020 and that met the inclusion criteria were reviewed addressing formulation development strategies, their limitations, and future perspectives regarding protection of intellectual property. Simultaneously, a microemulsion containing CBD (CBD-ME) was developed and characterized in terms of macroscopic aspect, pH, isotropy, conductivity, surface tension, droplet size distribution and encapsulation efficiency. In addition, the microemulsion was lyophilized and its stability in simulated gastric and intestinal fluids and for 90 days were also analyzed through measurements of droplet size and polydispersity index. Therefore, a microemulsion system containing CBD for oral administration and a review of the literature were obtained. The results showed that there were no significant differences in the parameters evaluated in the ME after the incorporation of approximately 1.65 mg CBD/ml oil phase (p>0.05). ME and CBD-ME were optically clear, homogeneous, and transparent systems, with a slightly yellowish color, without any precipitate or phenomenon of phase separation. In addition, they appeared dark under polarized light microscopy (no birefringence) and had refractive indices of 1.3894 ± 0.0001 and 1.3879 ± 0.0001, respectively. ME and CBD-ME had a pH of 6.2 ± 0.07 and 6.1 ± 0.09, respectively, considered physiologically acceptable for oral administration. The electrical conductivity and surface tension of ME and CBD-ME were 148 ± 22 and 140 ± 16 µS/cm and 40.53 ± 1.8 and 41.98 ± 2.1 dynes/cm, respectively. The mean droplet size was 20 ± 0.4 nm with PdI of 0.151 ± 0.07 and 22 ± 0.6 nm with PdI of 0.127 ± 0.08 (p-values > 0.05) for ME and CBD- ME, respectively. Mean droplet size and PdI of ME and CBD-ME before and after lyophilization did not show significant changes after dilution and incubation in simulated gastrointestinal fluids (p>0.05). CBD-ME lyophilized and stored at 4°C exhibited the highest stability with a size of 21.4 ± 0.4, a PdI of 0.205 ± 0.003 and an encapsulation efficiency of 98.8 ± 0.9% after finishing of the 90-day period of this study. Therefore, our results indicate that CBD-ME stored under these conditions is potentially suitable for use as an oral CBD delivery system.