Direct Extraction of Hemp Leaf-Derived Cannabidiol (CBD) and Encapsulation into Biopolymer Nanoparticles for Diffusion-Based Drug Release

Cannabis sativa L. (hemp) is a renewable source of cannabinoids such as cannabidiol (CBD) and tetrahydrocannabinol (THC), known for their antioxidant and therapeutic properties. However, their clinical application is limited by poor water solubility, instability, and low bioavailability. This study explores the use of biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles to improve cannabinoid delivery. Cannabinoids were directly extracted from hemp leaves using ethanol maceration, yielding an extract rich in CBD (ca. 76 mg/g), with high antioxidant activity (IC₅₀ DPPH ca. 100 µg/mL), total phenolic content (ca. 81 mg GAE/g), and flavonoid content (ca. 20 mg QE/g). The extract was encapsulated in PLGA nanoparticles using a simple single emulsion evaporation method. Key formulation parameters, polymer concentration, homogenization time, O/W phase ratio, surfactant concentration, and cannabinoid concentration were optimized to achieve nanoparticle sizes below 200 nm, with high encapsulation efficiency and drug loading. The resulting nanoparticles exhibited a consistent size distribution, with reproducible diameters, high encapsulation efficiency (up to 98%), drug loading (ca. 7%), and storage stability for at least six months. In vitro drug release, assessed via direct dispersion and dialysis methods, revealed an initial burst profile followed by sustained release. Cytotoxicity assays were conducted using human colorectal carcinoma cells to demonstrate the non-cytotoxic nature of our nanoparticulate systems. This work highlights the potential of hemp leaf-derived cannabinoids in PLGA nanoparticle systems for controlled drug delivery. The approach offers a sustainable and scalable strategy to enhance cannabinoid bioavailability and therapeutic application.