Sodium alginate/N-(Vinylcaprolactam) based supramolecular self-assembled subcutaneously administered in situ formed gels depot of 5-fluorouracil: Rheological analysis, in vitro cytotoxic potential, in vivo bioavailability and safety evaluation.

In current study, novel in situ formed injectable self-assembled thermoreversible depot gels based on N-(Vinylcaprolactam) were synthesized with a carbohydrate polymer i.e. sodium alginate in aqueous solution using cold method. The prepared gels preparations were intended to be utilized as 5-FU delivery depot after injectable administration through subcutaneous route. The structural characterization of self-assembled gels samples were studied through FTIR. The thermal properties of newly formed gels complexes were investigated by DSC and TGA. While the morphology of gels were assessed through SEM. The tunable gelation temperatures and phase transition of optimized formulations were confirmed by tube inverting, rheology determination and optical transmittance test. Thermo and pH response was evaluated at different temperatures and in various acidic and basic buffer solutions. In vitro release experiments were conducted using Franz diffusion system to monitor the controlled delivery fashion of gels matrices. Results concluded that depot gels exhibit controlled delivery fashion with maximum release at pH 7.4 and 37 ± 2 °C. The biocompatible nature of blank gels samples was assessed by MTT assay against Vero cell lines and was found safe. While killing ability of 5-FU encapsulated gels was evaluated against HeLa (19 ± 0.22 μg/ml; 23 ± 0.55 μg/ml) and MCF-7 (21 ± 0.06 μg/ml and 22 ± 0.34 μg/ml) cancer cell lines and were found effective to kill cancer cells. Histopathological study showed that gels depot is safe with no harmful effects on major organs. The in vivo bioavailability in rabbits showed controlled release (Cmax, 4465.78 ± 1.99 ng/ml) in comparison to free drug (Cmax, 4883.73 ± 3.32 ng/ml) administration after subcutaneous injection.