Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

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

R Rajagopalan¹ , Sanjay K Jain², Ankur Kaul³, Piyush Trivedi¹

¹Department of Pharmaceutics, School of Pharmaceutical Sciences, Rajiv Gandhi Technological University, Bhopal (M.P); ²Department of Pharmaceutics, Dr Harisingh Gour University, Sagar (M.P); ³Division of Cyclotron & Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences (INMAS), DRDO, New Delhi, India.

For correspondence:- R Rajagopalan Email: rajagopalan10@gmail.com Tel:+919179626663

Accepted: 19 August 2019 Published: 30 September 2019

Citation: Rajagopalan R, Jain SK, Kaul A, Trivedi P. Biodistribution and pharmacokinetic studies on topically-delivered technetium-99m-labeled 5-FU nanogel formulation for management of pre-cancerous skin lesions. Trop J Pharm Res 2019; 18(9):1977-1983 doi: 10.4314/tjpr.v18i9.28

© 2019 The authors.
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Abstract

Purpose: To prepare technetium-99m (^99m-Tc)-labelled nanogel loaded with 5-fluorouracil (5-FU) containing synthesized gallic acid-stearylamine (GA-SA) conjugate in order to reduce its systemic toxicity and provide site-specific delivery to skin lesions.

Methods: Lipid nanocarrier-based 1 % (w/w) 5-FU nanogel containing GA-SA conjugate was successfully formulated. Parameters that included pH, viscosity and entrapment efficiency were measured. Furthermore, 1 % (w/w) 5-FU nanogel and 1 % (w/w) 5-FU commercial formulations were radiolabelled with ^99m-Tc. The radiolabelled ^99m-Tc-5-FU nanogel and commercial formulations were subjected to successive preclinical assessments with respect to radiochemical stability, biodistribution, and gamma scintigraphy in BALB/c mice, and pharmacokinetic studies in New Zealand albino rabbits.

Results: The entrapment efficiency of 5-FU in the nanogel preparation was 82.12 ± 1.2 %. The 5-FU nanogel formulation exhibited excellent radiolabelling efficiency (> 93 %) and high stability. Skin/blood localization ratios of 274.93 and 167.89 were obtained for topical radiolabelled drug-loaded 5-FU nanogel formulation and 5-FU commercial formulation, respectively, after 1 h of administration. Gamma scintigraphy and biodistribution studies showed that topically administered ^99m-Tc-5-FU nanogel was distributed mostly in skin, when compared to marketed 5-FU formulation. Pharmacokinetic studies revealed low maximum activity in the blood (C_max = 34.20 µg/mL), with low intensity (AUC) for topically administered ^99m-Tc-5-FU nanogel formulation.

Conclusion: 5-FU nanogel enhances specific delivery of 5-FU at targeted sites and decreases its toxicity in tissues distant from the site of application. The results suggest that nanogel loaded with 5-FU containing synthesized GA-SA conjugate is a novel effective approach for the treatment of skin lesions.

Keywords: 5-Fluorouracil, Skin lesions, 99mTechnetium, Biodistribution, Pharmacokinetics, Gamma scintigraphy