title: Development of novel topical drug delivery system containing cisplatin and imiquimod for dual therapy in cutaneous epithelial malignancy.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Cisplatin delivery through protransfersome gel in combination with imiquimod may potentiate the activity against solid tumors of epidermal origin.
  
  
  CONCLUSIONS
  Data revealed that combination therapy considerably enhances antitumor efficacy of the drug for skin-cited malignancies.
authors: School of Pharmaceutical Sciences, Rajiv Gandhi Technical University , Bhopal, Madhya Pradesh , India .
authors: Vandana
authors: V
authors: Gupta
authors: Vipin
authors: V
authors: Dhote
authors: Bhola Nath
authors: BN
authors: Paul
authors: Piyush
authors: P
authors: Trivedi
mesh_terms: D000287:Administration, Topical; D000634:Aminoquinolines / Q000008:administration & dosage*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D000077271:Imiquimod; D051379:Mice; D008856:Microscopy, Fluorescence; D017208:Rats, Wistar; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000634:Aminoquinolines; D000077271:Imiquimod; D002945:Cisplatin
keywords: A-431 cell line; combination therapy; cutaneous squamous cell carcinoma; cytotoxic activity; flexible pro-vesicular system; topical gel