(M1430-12-82) Aceclofenac-Loaded Nanoparticulate Carriers with Enhanced Solubilization Using Deep Eutectic Solvents for Improved Transdermal Delivery

Purpose: The objective of this study was to prepare aceclofenac-loaded ultradeformable liposomes (ACF-DES-UDLs) using deep eutectic solvent and to evaluate drug solubilization and skin permeation.

Methods: Deep eutectic solvents (DES) were prepared by blending betaine as a hydrogen bond acceptor and propylene glycol(BP)/ethylene glycol(BE) as hydrogen bond donors at 80℃. The prepared DES were mixed with distilled water at a ratio of 7:3 to encapsulate DES in liposomal aqueous compartment. The solubility of aceclofenac in DES and the viscosity of DES were investigated, respectively. ACF-DES(BP)-UDLs and ACF-DES(BE)-UDLs were prepared by lipid film hydration and extrusion method with egg phosphatidylcholine and Tween 80 as edge activator. ACF-DES-UDLs were characterized in terms of particle size, polydispersity index, zeta potential, encapsulation efficiency, and TEM image. In vitro skin permeation of ACF-DES-UDLs compared with aceclofenac solution was evaluated using Franz diffusion cell.

Results: The solubility of ACF in the DES increased approximately 16,370 times compared to that of water. ACF-DES-UDLs were successfully prepared with a particle size near 100 nm and showed a uniform particle size distribution. The encapsulation efficiency of ACF-DES(BP)-UDLs and ACF-DES(BE)-UDLs are 51.6±2.3% and 49.6±4.6%, respectively. Particle size, polydispersity index, zeta potential, and encapsulation efficiency of ACF-DES UDLs were not significantly changed at 4°C for 4 weeks while there were significant changes were observed at 25°C. The skin permeation parameters of ACF-DES(BP)-UDLs and ACF-DES(BE)-UDLs were 2.4 times and 1.71 times higher than ACF solution, respectively.

Conclusion: Based on these results, ACF-DES-UDLs have the potential to be used as transdermal nanocarriers for high-does aceclofenac treatment.

Physicochemical properties of ACF-DES-UDLs

In vitro skin permeation parameters of ACF-DES-UDLs