Elastic Liposomal Formulation for Sustained Delivery of Colchicine: In Vitro Characterization and In Vivo Evaluation of Anti-gout Activity

• Published in: The AAPS journal 2009-03, Vol.11 (1), p.54-64
• Main Authors: Singh, Hardevinder Pal, Utreja, Puneet, Tiwary, Ashok Kumar, Jain, Subheet
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Colchicine - administration & dosage; Colchicine - pharmacokinetics; Colchicine - therapeutic use; Delayed-Action Preparations; Drug Carriers; Drug Evaluation, Preclinical; Edema - drug therapy; Elasticity; Gout Suppressants - administration & dosage; Gout Suppressants - pharmacokinetics; Gout Suppressants - therapeutic use; Liposomes; Microscopy, Confocal; Pharmacology/Toxicology; Pharmacy; Rats; Rats, Wistar; Research Article; Skin - drug effects; Skin - ultrastructure; Skin Absorption
• ISSN: 1550-7416; 1550-7416
• DOI: 10.1208/s12248-008-9078-8

Colchicine, an alkaloid found in extracts of the plants Colchicum autumnale and Gloriosa superb , is effective in the treatment of acute gout and dermatological conditions like leuko-cytoclastic vasculitis, psoriasis, and Sweet’s syndrome. Oral administration of colchicine is associated with gastrointestinal side effects and its accumulation in the body leads to bone marrow suppression. In the present study, an attempt has been made for development and in vitro and in vivo evaluation of elastic liposomal formulation for topical delivery of colchicine. The in vitro skin permeation study across rat skin found transdermal flux for different elastic liposomal formulations to range between 32.8 ± 1.2 and 44.4 ± 1.9 μg h −1 cm −2 , which was approximately seven to 11 times higher than obtained using drug solution (4.3 ± 0.6 μg h −1 cm −2 ). The results of skin deposition study showed that elastic liposomal formulation provide 12.5-fold higher skin deposition as compared to drug solution of colchicine. Confocal laser scanning microscopy also revealed better accumulation and deeper penetration (up to 200 μm) of elastic liposomes than drug solution (up to 12 μm). The biological evaluation of various vesicular formulations and drug solution was carried out using monosodium urate-induced air pouch model. The results of anti-gout activity in rats showed better and sustained biological effects in 24 h measured in terms of exudate volume (63.1 ± 5.7% and 9.6 ± 0.5% reduction with elastic liposomes and drug solution, respectively), reduction in leukocyte count (74.2 ± 6.0% and 4.1 ± 0.3% reduction with elastic liposomes and drug solution, respectively), decrease in inflammatory cells accumulation, and collagen deposition with elastic liposomal formulation than drug solution. Hence, the present study reveals that elastic liposomal formulation of colchicine possesses greater potential to enhance skin accumulation, prolong drug release, and improve the site-specificity of colchicine.