Due to high lipophilicity and extensive first-pass metabolic loss, cannabidiol (CBD) has low oral bioavailability. Co-administration of CBD and long-chain lipids facilitates the intestinal lymphatic delivery, resulting in higher systemic bioavailability, as well as high levels of the drug within the intestinal lymphatic system. However, despite previous attempts with various lipid-based formulations, the oral bioavailability of CBD is still limited. In this work, we have developed a novel formulation of CBD based on natural rapeseed oleosomes. In vivo studies in rats demonstrated that oral administration of CBD-loaded rapeseed oleosomes leads to substantially higher oral bioavailability and intestinal lymphatic targeting of CBD in comparison with rapeseed oil or artificial emulsion made of rapeseed oil and lecithin. In vitro mechanistic assessments, including in vitro lipolysis and peroxide value determination suggest that the lower oxidative state of the oil in oleosomes in comparison to crude oil or artificial emulsion is likely to be the main factor responsible for the superior performance of the CBD-loaded rapeseed oleosomes in vivo. Although further investigation will be needed, the data suggest that natural seeds-derived oleosomes can be used as a promising lipid-based drug delivery platform promoting the bioavailability and lymphatic delivery of lipophilic drugs.
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