title: Topical delivery of fluorescence (6-Cf) labeled and radiolabeled (99m-Tc) cisplatin and imiquimod by a dual drug delivery system.
abstract: The present investigation deals with the development of topical (top.) formulation for co-delivery of cisplatin and imiquimod to enhance the antitumor efficacy of the drug for skin-cited malignancies even in immune compromised patient. Cisplatin (CDDP) and imiquimod-loaded protransfersome gel (CDDP-Imi-Pts gel) formulation was characterized for entrapment efficiency, pH, and viscosity. Further, fluorescence-labeled (6-carboxyfluorescin) and radiolabeled ((99m) technetium) drug-loaded formulations were compared with respect to biodistribution and pharmacokinetic studies. Gamma scintigraphy of mice following radiolabeled formulation administrations was performed to accomplish the localization of drugs in various organs. The percentage entrapment efficiency of cisplatin and imiquimod in the protransfersome gel formulations were found to be 36.22 ± 6.41 and 63.11 ± 3.73. The skin/blood localization ratio of 1.096, 120.13, 0.174, and 349.88 was found for intraperitoneal radiolabeled drug solution ((99m-)Tc-CDDP-Imi-Sol), top. radiolabeled drug-loaded protransfersome gel formulation ((99m-)Tc-CDDP-Imi-Pts gel), intraperitoneal 6-carboxyfluorescin labeled drug solution (6-Cf-CDDP-Imi-Sol), top. 6-carboxyfluorescin labeled drug-loaded protransfersome gel formulation (6-Cf-CDDP-Imi-Pts gel), respectively after 0.5h of administration. CDDP-Imi-Pts gel has a potential for site specific delivery and reduces the systemic toxicity of anti cancer drugs. These findings suggest that the cisplatin-imiquimod co-delivery offers an attractive, novel approach for treatment of skin-cited malignancies.
authors.affiliation: School of Pharmaceutical Sciences, Rajiv Gandhi Technical University, Gandhi Nagar, Airport Bypass Road, Bhopal, 462033, India.
authors.forename: Vandana
authors.initials: V
authors.lastname: Gupta
authors.forename: Krishna
authors.initials: K
authors.lastname: Chuttani
authors.forename: Anil K
authors.initials: AK
authors.lastname: Mishra
authors.forename: Piyush
authors.initials: P
authors.lastname: Trivedi
mesh_terms: D000287:Administration, Topical; D000634:Aminoquinolines / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D002945:Cisplatin / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D005452:Fluoresceins / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000737:chemistry; D000077271:Imiquimod; D007553:Isotope Labeling; D051379:Mice; D010539:Permeability; D011877:Radionuclide Imaging; D012867:Skin / Q000000981:diagnostic imaging / Q000378:metabolism; D013667:Technetium / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D000634:Aminoquinolines; D000970:Antineoplastic Agents; D005452:Fluoresceins; D005456:Fluorescent Dyes; C024098:6-carboxyfluorescein; D013667:Technetium; D000077271:Imiquimod; D002945:Cisplatin
keywords: 6-carboxyfluorescin; 99mtechnetium; biodistribution; co-delivery; pharmacokinetic