Preparation and evaluation of aceclofenac-loaded nanoparticulate carriers using deep eutectic solubilization technology for efficient transdermal delivery

Abstract

The purpose of this study was to investigate high drug loading and enhanced skin permeation of solubilization of aceclofenac in Deep Eutectic Solvent loaded ultradeformable liposomes (ACF-DES-UDLs). Deep eutectic solvents (DESs) are solvents that attract attention for their melting and stabilizing properties as well as low toxicity and biodegradability. We designed a new DES with a molar ratio of 1:4 based on betaine, propylene glycol, and ethylene glycol. DES identified physical properties and increased solubility by a fold of 16,370 (from 20 μg/mL to 327.4 mg/mL) compared to the solubility in ACF water. ACF was solubilized using DES and then loaded into UDL. ACF-DES-UDLs were prepared by lipid film hydration and extrusion method with egg phosphatidylcholine as a bilayer and TW80 as an edge activator. The physical chemical properties of ACF-DES-UDLs were described in treatments of particle size, zeta potential, polydispersity index and entrapment efficiency. The deformability of ACF-DES-UDLs was compared with that of ACF-DES-loaded conventional liposomes (ACF-DES-CLs) using a steel pressure filter device. aceclofenac release from ACF-DES-UDLs was assessed by Dialysis membrane methods. In vitro skin permeation of aceclofenac was evaluated using Franz diffusion cell and skin permeation parameters were compared between ACF-Sol and ACF-DES-UDLs. ACF-DES-UDLs were successfully prepared with a particle size near 100 nm and showed a uniform particle size distribution. The entrapment efficiency of ACF-DES(BP)-UDLs and ACF-DES(BE)-UDLs at 51.6 ± 2.3% and 49.6 ± 4.6 %, respectively. In vitro release and deformability of ACF-DES-UDL were not different from ACF-DES-CLs. The skin permeation parameters of ACF-DES(BP)-UDLs and ACF-DES(BP)-CLs were 2.4 times and 1.33 times higher than ACFsol, respectively.