Formulation optimization of pH-sensitive liposomes based drug delivery of Carboplatin and anti-proliferative evaluation against A549 (human lung carcinoma) cell lines

Abstract

The developments of pH–sensitive liposomes which are stable at physiological pH i.e. (6.8–7.4) have not explored much up until now. These lipid vesicles will go through destabilization and attain fusogenic properties in acidic conditions leading to liberation of aqueous contents. Carboplatin, included in the family of alkylating agent was found to exhibit adverse effects like myelo suppression, ion thrombocytopenia and leucopenia. Therefore, in order to circumvent these effects, carboplatin pH-sensitive liposomes for specific delivery is the ideal criteria and it poses a great challenge since the water-soluble drugs exhibited very low entrapment efficiency. The essential portion of study was evaluated using the Design Expert software 8. The pH-sensitive liposomes were optimized using Central composite design and one factor Response surface model design method and were prepared by film hydration method. Two formulation variables like drug: lipid ratio (X1) and volume of hydration media (X2) used to vary at three different levels and the other three variables viz. temperature, speed of rotation and vacuum applied were kept constant. The Response surface and contour plots were figured to elicit the effects of interaction of variables on the overall entrapment efficiency. pH-sensitive liposomes of carboplatin have been regarded as a promising delivery systematic approach in order to target tumor tissue as evaluated by the pre-clinical studies in both in vitro and ex-vivo conditions.