Targeted Oral Delivery of Exosomal Formulation of Cannabidiol against Lung Cancer

Abstract

Despite advances in the treatment of lung cancer, the survival rate remains low due to lack of specificity and selectivity. The use of appropriate nano-drug delivery vehicle can overcome these issues. Cannabidiol (CBD) has the potential to be used as a novel therapeutic agent for treating cancer. The study utilizes colostrum-derived exosomes as nano-carriers for the delivery of CBD to overcome its low oral bioavailability. Exosomes are isolated from colostrum powder by sequential ultracentrifugation. Following CBD loading the formulations (ExoCBD and FA-ExoCBD) are characterized for their physical parameters (size, charge, and zeta potential). Cell culture assays (MTT, colony forming) are performed to analyze the anti-cancer activity of CBD and ExoCBD against drug-sensitive and resistant lung cancer cells and followed by orthotopic lung tumor xenograft mouse-model. FA-functionalized exosomal formulation of CBD provides a drug load of 20–24%. CBD and its exosomal formulations show antiproliferative and anti-inflammatory activities against both lung cancer cells and reduce the colony forming ability. Mechanistically, CBD decreased the expression of CB2, cell cycle markers, NF-κB, and IκBα, while increasing GPR3 levels in both drug-sensitive and drug-resistant lung cancer cells, as well as MDR-1 in drug-resistant cells. Orally administered FA-ExoCBD shows superior tumor growth inhibition as compared to free CBD (80% vs 60%) at one-half the dose of 7.5 mg kg⁻¹ versus 15 mg kg⁻¹. FA-ExoCBD can be developed as a potential targeted oral drug in the quest of lung cancer management.