Thermoresponsive biomaterial system of irinotecan and curcumin for the treatment of colorectal cancer: in-vitro and in-vivo investigations.

Abstract

This study aims to develop a thermoresponsive biomaterial system of irinotecan (IRT) and curcumin (CUR) nano-transferosomal gel (IRT-CUR-NTG) for targeting colorectal cancer (CRC). The IRT-CUR-NTs were statistically optimized and loaded into poloxamer-based thermosensitive gel. Transmission electron microscopy (TEM), Differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR) of the IRT-CUR-NTs were performed, whereas pH, gelation time, gelation temperature, gel and mucoadhesive strength of the IRT-CUR-NTG were investigated. In-vitro release and anticancer analyses were explored using HT29 cells. Additionally, in-vivo pharmacokinetics study was investigated followed by histopathological examination and in-vivo anticancer analysis. The PS, PDI, ZP, %EE of IRT and %EE of CUR were found to be 136.15 nm, 0.143, -15.5 mV, 95.05% and 85.12%, respectively. IRT-CUR-NTs exhibited spherical shape with no chemical interactions among the constituents. Similarly, IRT-CUR-NTG was homogenous gel suitable for rectal administration. IRT-CUR-NTG manifested prolonged release profiles of IRT and CUR. Moreover, a significantly enhanced (4-fold) bioavailability and no toxicity of IRT-CUR-NTG was observed when compared with conventional gel. IRT-CUR-NTs were found to be more effective against HT29 cell lines. In-vivo antitumor analysis demonstrated significantly reduced tumor volume and tumor mass after treatment with IRT-CUT-NTG, indicating improved antitumor effect. It can be concluded that IRT-CUR-NTG is suitable biomaterial system for colorectal cancer.