Nanotechnology-Driven Colorectal Cancer Treatment: Coencapsulation of Irinotecan and Cyclosporine A in SNEDDS for Superior Outcomes.

Irinotecan (IRN), a camptothecin derivative, has limited and inadequate oral absorption due to efflux pump activity by intestinal P-glycoprotein receptors. To complete these challenges, we designed and fabricated irinotecan and cyclosporine. A coloaded self-nanoemulsifying drug delivery system (CO-IR-CP-SNs) can effectively prevent P-gp efflux and P450 enzyme metabolization, increasing oral bioavailability. To date, this combination has not been reported, which gives uniqueness to our formulation. The CO-IR-CP-SNs were fabricated by using the Box-Behnken design tool with Capryol 90, Cremophor EL, and PEG-400 as the oil, surfactant, and co-surfactant, respectively. The optimized CO-IR-CP-SNs had an average globule size of 16.36 ± 1.09 nm and a polydispersity index of 0.250 ± 0.01. The combination index value supports the existence of synergy in human colorectal cancer cell lines (HCT-116). The combination index shows a value of 0.78, which is <1, indicating synergism. Coloaded SNEDDS (CO-IR-CP-SNs) showed greater cellular uptake, reactive oxygen species generation, and apoptosis. In vivo pharmacokinetic studies demonstrated a 14-fold and 6.08-fold increase in C_max and increased bioavailability compared with pure drug suspensions of IRN and CSP, respectively. Systemic toxicity signifies the nontoxic nature of CO-IR-CP-SNs in comparison to pure drug solutions of irinotecan and cyclosporine, individual and in combination. Hence, CO-IR-CP-SNs show promising results and improved oral bioavailability, which is beneficial in anticancer therapy with minimal side effects associated with the drug.