In an attempt to improve the localized paclitaxel delivery, carrier based thermoresponsive chitosan
hydrogel was exploited in the present study. Nanoliposomes as carrier for paclitaxel were prepared and optimized
in strength of 6 mg/ml similar to marketed paclitaxel formulation. The chitosan solution (2% w/v) mixed with
different concentrations of dibasic sodium phosphate (DSP) was evaluated as thermoresponsive systems in terms
of gelling temperature and time. Finally, the drug loaded nanoliposomes were incorporated in optimized chitosan-
DSP hydrogel base to form nanoliposomal in situ thermosensitive hydrogel formulations having dual mechanism
of protection and release. The optimal formulation containing DSP was selected on the basis of minimal gelation
temperature (37±0.8 ºC) and time (6.7±0.3 min). In vitro drug release experiment illustrated that developed
formulation manifested sustained release action in which drug release was extended for more than 72 h compared
to marketed formulation. In addition, optimized nanoliposomal hydrogel demonstrated enhanced biological half-life of 15.7±1.5h,
depicting maintenance of constant plasma concentration in contrast to marketed formulation that showed the half-life (t1/2) of 3.6±0.4h.
The in vivo anti tumor activity tested using EAC model also corroborated the above findings that developed formulation was having
significant higher anti-tumor activity and reduced toxicity than the marketed formulation. Tumor volume was found to reduce upto
89.1±3.5% by treatment with in situ hydrogel formulation. The histopathological study of tumor also demonstrated the better safety and
efficacy of developed formulation in comparison to marketed paclitaxel formulation. Our results suggest that carrier based chitosan
hydrogel could be an efficacious vehicle for sustained and localized delivery of paclitaxel.
Keywords: Anti-cancer activity, drug-carrier-hydrogel, dual approach, in situ gel formation, in situ nanoliposome hydrogel, paclitaxel,
sustained localized delivery.
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