Development of novel topical drug delivery system containing cisplatin and imiquimod for dual therapy in cutaneous epithelial malignancy

Abstract

CONTEXT: Strategy of dual therapy has been proposed to minimize the amount of each drug and to achieve the synergistic effect for cancer therapies. OBJECTIVE: The aim of this study was to develop an effective drug delivery system for the simultaneous topical delivery of two anti-tumor agents, cisplatin and imiquimod. MATERIAL AND METHODS: The preformulation studies were carried out in terms of tests for identification, solubility profile, determination of partition coefficient and simultaneous estimation of both drugs by UV-Visible spectrophotometer and High Performance Liquid Chromatography (HPLC). Drug-drug and drug-excipients interactions were examined by thin layer chromatography, infrared spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Provesicular drug delivery system (protransfersome gel formulation) have been prepared and characterized by in vitro and in vivo parameters. RESULTS: The mean size, poly dispersity index (PDI) and zeta potential of transfersomal vesicles formed by protransfersome hydration were 429.5 nm, 0.631 and -68.1 Mv, respectively. The prepared formulation showed toxicity on cutaneous squamous cell carcinoma cell line (A-431) at 200 µg (cisplatin) and 1 mg (imiquimod) concentration of drug in combination against control. The cisplatin- and imiquimod-loaded provesicular dual-drug delivery system achieved an optimal antitumor effect, increase in lifespan, antiviral, and toxicity reduction, revealing the advantage of site specific drug delivery and the modified combination therapy. DISCUSSION: Cisplatin delivery through protransfersome gel in combination with imiquimod may potentiate the activity against solid tumors of epidermal origin. CONCLUSION: Data revealed that combination therapy considerably enhances antitumor efficacy of the drug for skin-cited malignancies.