Development and In vitro kinetic evaluation of PEG-chitosan biohybrid micelles loading CBD with bile acid/quercetin as surface modifiers for colon cancer therapy.

Treatment for colon cancer is an intricate endeavor that demands innovative strategies for increasing the efficacy while lowering mortality and adverse effects. This study investigates the viability of delivering CBD to colon cancer cells by employing biohybrid micelles for oral delivery. These micelles are made of polyethylene glycol (PEG) and chitosan with bile acid and quercetin on the surface to synergistically increase CBD's anticancer benefits at lower doses and with fewer adverse effects. Chitosan's mucoadhesion and penetration facilitate PEG controlled release. The morphology, crystalline nature, stability, encapsulation efficiency (EE = 77.3 % ± 2 %), and composition of the biohybrid micelles are examined by using SEM, TEM, XRD, HPLC, FTIR, and TGA. IC50 values in μM (HCT116: 9.871 ± 0.244, HT29: 17.110 ± 2.515, Caco-2: 20.023 ± 2.685), colon cancer cell lines showed treatment with these micelles reduced cell survival in a dose-dependent manner relative to free CBD. Apoptosis investigations revealed increased caspase-3/7 activity by biohybrid micelles along with upregulation of Bax expression and downregulation of Bcl-2 expression confirmed by ELISA. Efficiency of component release from biohybrid micelles at varying pH levels is assessed after 72 h at pH 1.2, 6.8, and 7.4 (n ≥ 3). Drug release rates: Bile acid surpasses quercetin, which exceeds CBD (p < 0.05). This innovative drug delivery technique improves CBD colon cancer treatment by combining controlled release with quercetin synergy, laying a foundation for clinical trials.