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

  • Worranan Rangsimawong
  • Yasuko Obata
  • Praneet Opanasopit
  • Tanasait Ngawhirunpat
  • Kozo Takayama
Research Article
  • 51 Downloads

Abstract

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 WORDS

sonophoresis PEGylated liposomes limonene skin penetration mechanism 

Abbreviations

Chol

cholesterol

CLSM

confocal laser scanning microscopy

DPH

1,6-diphenyl-1,3,5-hexatriene

DSC

differential scanning calorimetry

ED

epidermis and dermis

EMA

European Medicines Agency

FDA

Food and Drug Administration

FTIR

Fourier transform infrared spectroscopy

GLT

galantamine HBr

NaFI

sodium fluorescein

PC

egg phosphatidylcholine

PEG2000-DSPE

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

PL

PEGylated liposomes

PL-LI

limonene-containing PEGylated liposomes

Rhodamine PE

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

SC

stratum corneum

SD

standard deviation

SN

sonophoresis

Tm

transition midpoint temperature

Notes

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
  • 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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