AAPS PharmSciTech

, Volume 19, Issue 3, pp 1093–1104 | Cite as

Enhancement of Galantamine HBr Skin Permeation Using Sonophoresis and Limonene-Containing PEGylated Liposomes

  • Worranan RangsimawongEmail author
  • Yasuko Obata
  • Praneet Opanasopit
  • Tanasait Ngawhirunpat
  • Kozo Takayama
Research Article


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.


sonophoresis 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


galantamine HBr


sodium fluorescein


egg phosphatidylcholine


Na-salt N-(carbonyl-methoxypolyethylene glycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine


PEGylated liposomes


limonene-containing PEGylated liposomes

Rhodamine PE

rhodamine B 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine triethylammonium salt


stratum corneum


standard deviation




transition midpoint temperature


Funding Information

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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Copyright information

© American Association of Pharmaceutical Scientists 2017

Authors and Affiliations

  • Worranan Rangsimawong
    • 1
    Email author
  • Yasuko Obata
    • 2
  • Praneet Opanasopit
    • 1
  • Tanasait Ngawhirunpat
    • 1
  • Kozo Takayama
    • 3
  1. 1.Department of Pharmaceutical Technology, Faculty of PharmacySilpakorn UniversityNakhon PathomThailand
  2. 2.Department of PharmaceuticsHoshi UniversityTokyoJapan
  3. 3.Faculty of Pharmacy and Pharmaceutical SciencesJosai UniversitySaitamaJapan

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