Date on Master's Thesis/Doctoral Dissertation
8-2024
Document Type
Master's Thesis
Degree Name
M.S.
Department
Pharmacology and Toxicology
Degree Program
Pharmacology and Toxicology, MS
Committee Chair
Gupta, Ramesh
Committee Member
Aqil, Farrukh
Committee Member
Hein, David
Committee Member
Klinge, Carolyn M.
Committee Member
Schultz, David
Author's Keywords
Exosomes; cannabidiol; targeted drug delivery; oral delivery; breast cancer
Abstract
Cancer therapies are limited by lack of specificity, selectivity and numerous adverse effects. Repurposing potential anticancer compounds with appropriate drug carriers can help overcome these drawbacks. In our present study, we address the major obstacle for cannabidiol (CBD): its low oral bioavailability, using exosomes. Exosomes (Exo) are promising non-toxic and biocompatible drug delivery vehicles Our project aims are to address the research gap by formulating exosomal cannabidiol (ExoCBD): a tumor-targeted oral delivery system for the treatment of breast cancer. The targeting approach relies on the overexpression of folate receptors at the tumor site by using folic acid functionalized exosomes (FA-Exo). We loaded CBD onto the exosomes with 20 % drug load. The CBD-loaded exosomal formulations were well within the nanometric range and had an average size of 123 ± 2.4 nm. Triple-negative breast cancer (TNBC) cell lines – MDA-MB-231 and MDA-MB-231TR were more sensitive to CBD treatment as compared to MCF-7 and MCF-7TR. CBD exerted its anti-cancer effect by downregulating anti-apoptotic markers, anti-inflammatory maker at protein level. The ExoCBD formulation when administered orally, showed higher efficacy than the free drug (55 % vs 34%) against the orthotopic breast tumor growth. The efficacy was further enhanced to 68% with FA-ExoCBD. We also observed that ExoCBD showed higher levels of CBD as compared to free CBD in plasma, liver, and mammary pads upon oral administration of a single high dose. Thus, FA-ExoCBD can be further advanced as a cancer therapeutic considering its advantages such as low effective dose, with anti-inflammatory and pain-relieving effects.
Recommended Citation
Moholkar, Disha Nagesh, "Exosomal cannabidiol: A promising candidate for targeted oral delivery against breast cancer." (2024). Electronic Theses and Dissertations. Paper 4428.
Retrieved from https://ir.library.louisville.edu/etd/4428
