Combination of elastic liposomes and low frequency ultrasound for skin permeation enhancement of hyaluronic acid

• The developed hyaluronic acid (HA) loaded elastic liposomes (ELs) showed elliptical shape with a mean size of ∼700 nm and a zeta potential of ∼−40 mV.
• The amount of cholesterol played a significant role in controlling vesicle size and elasticity of liposomes which correspond with permeation study.
• The low frequency ultrasound (LFU) exposure time was found to associate with drug penetration as well as skin perturbation.
• The in vitro permeation study revealed that combination of LFU and ELs showed permeation enhancing effect for transepidermal delivery of HA than that ELs alone and HA solution with LFU, 2.1 times and 6.4 times, respectively.

HypothesisThe synergistic approach of using elastic liposomes (ELs) and low frequency ultrasound (LFU) was developed to enhance transepidermal delivery of hydrophilic macromolecules, hyaluronic acid (HA).ExperimentHA loaded ELs were prepared with varying cholesterol contents by reverse phase evaporation technique. Their mean sizes were evaluated using dynamic light scattering. Entrapment efficacy (%EE) was determined by UV–vis spectrophotometry. In vitro permeation studies using porcine ear epidermis were investigated. In addition, skin barrier disruption was assessed by transepidermal water loss and histology.FindingsThe HA loaded ELs showed mostly elliptical shaped with a mean size of ∼700 nm and a zeta potential of ∼−40 mV. Up to 77% drug entrapment efficiency was achieved. As ELs cholesterol content decreased, vesicle size, elasticity of liposomes and HA permeation profile increased. The in vitro permeation studies demonstrated that HA solution cannot permeate through the porcine epidermis. The combination of ELs/LFU showed greater HA permeation than ELs and HA/LFU, 2.1 times and 6.4 times, respectively. Increased LFU exposure times augmented HA permeation, but greater skin disruption was observed. Nevertheless, no skin damage was observed at the optimized 1 min exposure time. This ELs/LFU combination provides an efficacious protocol for transcutaneous drug delivery.

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