An update of nano-based drug delivery systems for cannabinoids: Biopharmaceutical aspects & therapeutic applications

Nanotechnology has been widely used to improve stability, efficacy, release control and biopharmaceutical aspects of natural and synthetic cannabinoids. In this review, the main types of cannabinoid-based nanoparticles (NPs) reported so far are addressed, taking into account the advantages and disadvantages of each system. Formulation, preclinical and clinical studies performed with colloidal carriers were individually analyzed. Lipid-based nanocarriers have been recognized for their high biocompatibility and ability to improve both solubility and bioavailability. Δ⁹-tetrahydrocannabinol-loaded lipid systems designed to treat glaucoma, for example, showed superior in vivo efficacy in comparison to market formulations. The analyzed studies have shown that product performance can be modulated by varying particle size and composition. In the case of self-nano-emulsifying drug delivery systems, the reduced particle size shortens the time to reach high plasma concentrations while the incorporation of metabolism inhibitors extends the plasma circulation time. The use of long alkyl chain lipids in NP formulations, in turn, is strategized to achieve intestinal lymphatic absorption. Polymer NPs have been prioritized when a sustained or site-specific cannabinoid release is desirable (e.g., CNS-affecting diseases/cancer). The functionalization of the surface of polymer NPs makes their action even more selective whereas surface charge modulation is highlighted to provide mucoadhesion. The present study identified promising systems for targeted applications, making the process of optimizing new formulations more effective and faster. Although NPs have shown a promising role in the treatment of several difficult-to-treat diseases, more translational studies should be performed to confirm the benefits reported here.