Background: Oxaliplatin (OXP), a 3rd generation platinum compound, which causes severe side effects
due to; impulse high concentration in the bloodstream thereby exposing healthy cells at a high ratio, nonspecific
delivery at the target site and non-compliance is administered intravenously.
Objective: The project was aimed at the development, characterization, and in-vitro and in-vivo evaluation of pHresponsive
hydrogels for oral administration of OXP.
Methods: 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, and MTT-assay. While in-vivo studies such as oral tolerability,
histopathology, and hematology studies were performed on rabbits. A simple and sensitive HPLC-UV method
was optimized and the comparative pharmacokinetic study was performed in rabbits using OXP-oral solution and
Results: 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 dosedependent
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.
Conclusion: 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.