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.

Biodistribution and pharmacokinetic studies on topically delivered technetium-99m-labeled 5-FU nanogel formulation for management of pre-cancerous skin lesions

“…The resultant sediment was resuspended in 0.2 % Triton x-100 (1 mL), and the UV absorbance of the suspension was measured. The total amount of drug comprised the drug present in both sediment and supernatant [14]. The drug content was analysed using UV-1700 spectrophotometer (Shimadzu, India).…”

Synergistic Cytotoxic Effect of Imiquimod and Cisplatin Combination Therapy on A549 Lung Cancer Cell

“…13 Numerous studies demonstrated that co-delivery of chemo agents such as OXA and Cis with TLR agonists strengthened the antitumor effect and reduces systemic and immune toxicity compared with chemotherapy alone. 1,11,14,15 The present study attempted to find out whether combination therapy with IMQ, an immune system modulator, plus Cis as ICD inducer agent can trigger potent tumor cell apoptosis with lower cytotoxicity in the A549 lung cancer cell line.…”