Development, Characterization and In Vitro Evaluation of Cannabidiol Loaded Zeolite Nanoparticles

Abstract

Cannabidiol (CBD) has garnered significant attention for its medicinal potential, yet its oral bioavailability remains a challenge due to its high lipophilicity and extensive first pass metabolism. To overcome these limitations, innovative drug delivery systems are being explored, with zeolite-based nanocarriers emerging as a promising solution. Zeolites offer several advantages in drug delivery, including a high surface area for efficient drug loading, tunable pore sizes optimal for accommodating larger biomolecules, and admirable biocompatibility, making them ideal candidates for encapsulating sensitive compounds. This study investigates the development of an MCM-41 zeolite-based drug delivery system, with comprehensive characterization of the zeolite particles using thermogravimetric analysis (TGA), Brunauer Emmett Teller (BET), and Direct Light Scattering (DLS), before and after CBD loading. The study further examines CBD encapsulation efficiency, its release profile from the zeolite matrix, in vitro dissolution behavior in simulated gastric and intestinal fluids. Additionally, the study evaluates the in vitro cellular uptake and cytocompatibility of the loaded zeolite particles in Caco-2 cells. The results showed that the CBD-loaded zeolite particles exhibited a high encapsulation efficiency of 78.7%. BET and DLS analysis confirmed that the zeolite particles were successfully loaded with CBD. The in vitro dissolution of the MCM-41 zeolite loaded CBD particles showed significant difference when compared to CBD containing particles in a commercialized capsule after 15 min in both Simulated gastric fluid (pH 1.8) and Simulated intestinal fluid (pH 6.8) with 51.8 % versus 25.8 % and 48.7 % vs 29.5 % respectively. In addition, Cell Uptake studies demonstrated an increase in CBD internalization and retention by 2.4 folds for the USY loaded zeolite and 1.9 folds for the MCM-41 loaded zeolite when compared to CBD in its free form. Furthermore, cytotoxicity results showed that the concentrations used in the experiment were non-toxic to cells. Our findings support the potential of zeolites as an effective oral drug delivery system for enhancing the bioavailability of challenging drugs like CBD.