Development of enhanced drug delivery vehicles for three cannabis-based terpenes using poly(lactic-co-glycolic acid) based nanoparticles

Abstract

Terpenes derived from different varieties of Cannabis sativa have shown potentially useful pharmacological activities, including the ability to bind to transient receptor potential (TRP) channels. Beta-myrcene (MC), beta-caryophyllene (CPh), and nerolidol (NL) are among the most abundant and studied terpenes found in cannabis. Despite the potential pharmacological effectiveness of these terpenes, their volatile and hydrophobic nature, and associated poor solubility and low bioavailability limit their suitability as pharmaceutical agents. To address these limitations, the current study sought to design poly(DL-lactide-co-glycolide) (PLGA) based nanoparticles (NPs) that encapsulate MC, CPh, and NL. First, several preparation methods and formulations were tested to develop MC-loaded PLGA NPs. The NPs produced had a mean diameter between 200–350 nm, a narrow size distribution, and a negative zeta potential in the range of -25 to -30 mV. Optimal NPs were produced using emulsion-solvent evaporation, purified and collected by ultra-filtration, and freeze-dried in the presence of trehalose 5% (w/w), achieving the highest encapsulation efficiency (EE%: ∼8%). Utilizing the optimized formulation and preparation method, PEG-PLGA NPs encapsulating MC, CPh, or NL were also fabricated and characterized. The encapsulation capacities of CPh (EE%: 64.9 %) and NL (EE%: 55.7 %) PEG-PLGA NPs were approximately 3-fold that of MC NPs (EE%: 18.1 %). In conclusion, these three terpenes were successfully encapsulated in PLGA-based NPs. The nanosystems developed herein can be proposed as promising therapeutic tools for the enhanced delivery of cannabis-derived terpenes.