Enhancement of Galantamine HBr Skin Permeation Using Sonophoresis and Limonene-Containing PEGylated Liposomes
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This study aimed to investigate the effect of low-frequency sonophoresis (SN) and limonene-containing PEGylated liposomes (PL) on the transdermal delivery of galantamine HBr (GLT). To evaluate the skin penetration mechanism, confocal laser scanning microscopy (CLSM), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC) were employed. The application of SN led to more GLT penetration into and through the skin than GLT solution alone. The liposomes also improved GLT permeation, and 2% limonene-containing PL (PL-LI2%) exhibited the highest GLT permeation, followed by PL-LI1%, PL-LI0.1%, and PL. The CLSM images of PL-LI2% resulted in the highest fluorescence intensity of fluorescent hydrophilic molecules in the deep skin layer, and the rhodamine PE-labeled liposome membrane was distributed in the intercellular region of the stratum corneum (SC). PL-LI2% induced significant changes in intercellular lipids in the SC, whereas SN had no effect on intercellular lipids of the SC. DSC thermograms showed that the greatest decrease in the lipid transition temperature occurred in PL-LI2%-treated SC. SN might improve drug permeation through an intracellular pathway, while limonene-containing liposomes play an important role in delivering GLT through an intercellular pathway by increasing the fluidity of intercellular lipids in the SC. Moreover, a small vesicle size and high membrane fluidity might enhance the transportation of intact vesicles through the skin.
KEY WORDSsonophoresis PEGylated liposomes limonene skin penetration mechanism
confocal laser scanning microscopy
differential scanning calorimetry
epidermis and dermis
European Medicines Agency
Food and Drug Administration
Fourier transform infrared spectroscopy
Na-salt N-(carbonyl-methoxypolyethylene glycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine
limonene-containing PEGylated liposomes
- Rhodamine PE
rhodamine B 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine triethylammonium salt
transition midpoint temperature
We gratefully acknowledge the Thailand Research Funds through the Royal Golden Jubilee PhD Program (Grant No. PHD/0091/2554) for the financial support and thank for the Faculty of Pharmacy and Graduate School, Silpakorn University, Nakhon Pathom, Thailand and Department of Pharmaceutics, Hoshi University, Tokyo, Japan for all facilities and support. This work was supported by the MEXT-Supported Program for the Strategic Research Foundation at Private University, 2014-2018, S1411019.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflicts of interest.
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