Combination of elastic liposomes and low frequency ultrasound for skin permeation enhancement of hyaluronic acid.
OBJECTIVE
The synergistic approach of using elastic liposomes (ELs) and low frequency ultrasound (LFU) was developed to enhance transepidermal delivery of hydrophilic macromolecules, hyaluronic acid (HA).


METHODS
HA 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.


RESULTS
The 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.
Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok 65000, Thailand.
Chawankorn
C
Kasetvatin
Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok 65000, Thailand.
Soravoot
S
Rujivipat
Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok 65000, Thailand; The Center of Excellence for Innovation in Chemistry (PERCH-CIC), Commission on High Education, Ministry of Education, Thailand; The Center of Excellence in Medical Biotechnology, Naresuan University, Phitsanulok 65000, Thailand. Electronic address: wareet@nu.ac.th.
Waree
W
Tiyaboonchai
D000279:Administration, Cutaneous; D000818:Animals; D002784:Cholesterol / Q000737:chemistry; D016503:Drug Delivery Systems; D004548:Elasticity; D004817:Epidermis / Q000378:metabolism; D005079:Excipients; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D066298:In Vitro Techniques; D008081:Liposomes / Q000737:chemistry*; D010316:Particle Size; D012869:Skin Absorption / Q000187:drug effects*; D013552:Swine; D014465:Ultrasonics / Q000379:methods*; D014870:Water Loss, Insensible
D005079:Excipients; D008081:Liposomes; D006820:Hyaluronic Acid; D002784:Cholesterol
Elastic liposomes; Hyaluronic acid; Low frequency ultrasound; Transepidermal delivery