Mandip Sachdeva
Florida A&M University
Several studies have shown that cannabinoids possess anticancer activities including cell migration inhibition, anti-proliferation, apoptosis and anti-angiogenesis against various cancers including breast, skin, lung, prostate and glioblastomas. However, cannabinoids such as CBD have poor bioavailability (13-19%) when taken orally due to their first pass metabolism, high lipophilicity (log P values of > 5) and low aqueous solubility (2–10 μg/ml in water). Milk exosomes have shown promise as novel therapeutic possibilities for the treatment of several illnesses, including cancer. Human, bovine, porcine, horse, yak, sheep, and goat are among the species from which exosomes have been isolated. Exosomes derived from these milk sources have been reported to have anti-inflammatory, antioxidant, anticancer and antimicrobial properties. Camel milk and its components have been reported to possess anticancer activity against a range of cancer diseases. We explored the potential of Camel milk derived exosomes (CMDE) to enhance the bioavailability of CBD. CMDE, isolated and purified through differential ultracentrifugation, showed it to be a promising carrier due to their high yield and economical scalability compared to other sources. Our in-vitro cytotoxicity studies demonstrated the anticancer potential of CMDE against DOX resistant MDA-MD-231 and RM resistant MDA- MB-468 cell lines. In-vitro permeability studies using MDCK cells demonstrated the ability of CMDE to traverse tight junctions, while high drug loading and entrapment efficiency contributed to improved overall bioavailability of CBD. Specifically, our in-vivo pharmacokinetic study (PK) in SD rats revealed a significant enhancement in bioavailability for the CBD-CMDE compared to the control group. Furthermore, PK studies showed enhanced bioavailability of CBD from CBD-CMDE with AUC(0-24h) of 1350.56±187.50 ng/mL*h as compared to CBD control formulation with AUC(0- 24h) of 351.95±39.10ng/mL*h. Further CMDE containing Vybrant DiO when given to tumor bearing animals by the oral route was found localized in tumors which further supports our Pk observations. Overall, CMDE can be used to enhance the oral absorption of poorly bioavailable APIs making it a noteworthy contribution to the field.