Elastic Liposomal Formulation for Sustained Delivery of Colchicine: In Vitro Characterization and In Vivo Evaluation of Anti-gout Activity
Journal Title: The AAPS Journal - Year 2009, Vol 11, Issue 1
Abstract
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.
Authors and Affiliations
Hardevinder Pal Singh, Puneet Utreja, Ashok Kumar Tiwary, Subheet Jain
Keywords
Related Articles
- EP ID EP681447
- DOI 10.1208/s12248-008-9078-8
- Views 58
- Downloads 0
Ajulemic acid (IP-751): Synthesis, proof of principle, toxicity studies, and clinical trials
Ajulemic acid (CT-3, IP-751,1’,1’-dimethylheptyl-Δ8 acid) (AJA) has a cannabinoid-derived structure; however, there is no evidence that it produces psychotropic actions when given at therapeutic d...
Etoposide-incorporated tripalmitin nanoparticles with different surface charge: Formulation, characterization, radiolabeling, and biodistribution studies
Etoposide-incorporated tripalmitin nanoparticles with negative (ETN) and positive charge (ETP) were prepared by melt emulsification and high-pressure homogenization techniques. Spray drying of nanoparticles led to free f...
Erratum to: Pharmacokinetic and Pharmacodynamic Analysis of Hyperthermic Intraperitoneal Oxaliplatin-Induced Neutropenia in Subjects with Peritoneal Carcinomatosis
The online version of the original article can be found at http://dx.doi.org/10.1208/s12248-010-9249-2.
The Use of Betaine HCl to Enhance Dasatinib Absorption in Healthy Volunteers with Rabeprazole-Induced Hypochlorhydria
Many orally administered, small-molecule, targeted anticancer drugs, such as dasatinib, exhibit pH-dependent solubility and reduced drug exposure when given with acid-reducing agents. We previously demonstrated that beta...
Pharmacogenomic Biomarkers: an FDA Perspective on Utilization in Biological Product Labeling
Precision medicine promises to improve both the efficacy and safety of therapeutic products by better informing why some patients respond well to a drug, and some experience adverse reactions, while others do not. Pharma...