Vanaja Kenchappa*, Salwa, S. Narasimha Murthy and Shivakumar HN Pages 1 - 12 ( 12 )
Purpose: Topical therapy is ineffective in case of musculoskeletal disorders (MSD) as it is not able to maintain therapeutic levels of drug in the affected joint due to its inability to surpass the dermal circulation and penetrate into deeper tissues. One of the approaches to enhance deep tissue penetration of drugs is to increase drug delivery much above the dermal clearance. The objective of the present work was to formulate negatively charged deformable liposomes (DL) of diclofenac sodium (DS) using biosurfactants and target the same to the synovial fluid by application of iontophoresis.
Methods: Deformable liposomes loaded with diclofenac sodium were formulated and characterized for surface morphology, particle size distribution, zeta potential and entrapment efficiency. In vitro permeation of the diclofenac from aqueous solution, conventional liposomes, and deformable liposomes under iontophoresis was performed using Franz diffusion cells and compared to passive control. Intraarticular microdialysis was carried out to determine the time course of drug concentration in the synovial fluid at the knee-joint region of hind limb in Sprague Dawley rats.
Results: The vesicles were found to display a high entrapment (> 60%) and possess a negative zeta potential lower than -30 mV. The size of the vesicles was varied from 112.41 ± 1.42 nm and 154.6 ± 3.22 nm demonstrated good stability on application of iontophoresis. The iontophoretic flux values for the DS aqueous solution, conventional liposomes and deformable liposomal formulation were found to be 7.55 ± 0.42, 16.75±1.77and 44.01 ± 3.47 µg/ cm2 h-1 respectively. Deformable liposomes were found to display an enhancement of 5.83 fold compared to passive control. Iontophoresis was found to enhance the availability of DS deformable liposomes (0.56 ± 0.08 µg.h/ml) in the synovial fluid by nearly 2-fold over passive delivery (0.29 ± 0.05 µg.h/ml).
Conclusions: Results obtained indicate that iontophoretic mediated transport of deformable liposomes could improve the regional bioavailability of diclofenac sodium to the synovial joints, an efficient mode for treating MSD in elderly.
Iontophoresis, Liposome(s), Intraarticular, Deformable, Microdialysis, NSAID, Transdermal.
College of Pharmacy, Western University of Health Sciences, Pomona, California, Institute for Drug Delivery and Biomedical Research, Bangalore, Institute for Drug Delivery and Biomedical Research, Bangalore, Institute for Drug Delivery and Biomedical Research, Bangalore