Background and Objective: Topical therapy is ineffective in the case of Musculoskeletal
Disorders (MSD) as it is not able to maintain therapeutic levels of the 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 the 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 the 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).
Conclusion: 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 the elderly.