Oxaliplatin (OXP), a 3rd generation platinum compound, is administered intravenously which causes severe side effects due to; impulse high concentration in the bloodstream thereby exposing healthy cells at a high ratio, non-specific delivery at the target site and non-compliance.
The project was aimed at the development, characterization, and in-vitro and in-vivo evaluation of pH-responsive hydrogels for oral administration of OXP.
Hydrogel formulations were synthesized through a free radical polymerization technique followed by brief characterization using various techniques. The hydrogels were investigated for various in-vitro studies such as sol-gel, drug loading, swelling, drug release, MTT-assay. While in-vivo studies such as oral tolerability, histopathology, and hematology studies were performed in rabbits. A simple and sensitive HPLCUV method was optimized and the comparative pharmacokinetic study was performed in rabbits using OXPoral solution and OXP-loaded hydrogels.
In-vitro characterization confirmed that the reactant was successfully crosslinked to form thermally stable hydrogels with decreased crystallinity and rough surface. Swelling and drug release showed that hydrogels were more responsive to basic pH (6.8 and 7.4) in comparison with pH 1.2. The blank hydrogels were cytocompatible as more than 95% of the cells were viable while free OXP and OXP-loaded hydrogels displayed dose-dependent cytotoxic effect. In-vivo studies confirmed that chitosan and gelatin hydrogel suspension was well tolerable up to 3800 mg/kg and 4000 mg/kg of body weight respectively. Hematology and serum chemistry reports were well within the range suggesting normal liver and kidney functions. Similarly, histopathology slides of rabbit vital organs were also found normal without causing any histopathological change.
HPLC-UV method was successfully optimized for OXP detection in oral solution and hydrogels administered to rabbits. A significant difference was found among various pharmacokinetic parameters by comparing the two groups including half-life (t1/2), tmax, Cmax, AUCtot MRT, Vz , and Lz .
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