Fabrication and characterization of hyaluronic acid microneedles to enhance delivery of magnesium ascorbyl phosphate int
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Fabrication and characterization of hyaluronic acid microneedles to enhance delivery of magnesium ascorbyl phosphate into skin Yujin Kim 1 & Sonalika A. Bhattaccharjee 1 & Moritz Beck-Broichsitter 2 & Ajay K. Banga 1
# Springer Science+Business Media, LLC, part of Springer Nature 2019
Abstract This study investigated the in vitro transdermal delivery of magnesium ascorbyl phosphate (MAP) through porcine ear skin treated with hyaluronic acid (HA) microneedles (MNs). In this study, the micro-molding method was used to fabricate HA MNs. HA solution (10% w/v) containing 3% of MAP was placed onto a poly(dimethyl siloxane) mold to fill the microchannels under vacuum followed by drying in a desiccator. Scanning electron microscopy was performed to record the dimensions of the MNs. Skin microporation was demonstrated by dye binding. Histological skin sections revealed the shape of microchannels under hematoxylin-eosin staining. The actual depth of the microchannels and drug distribution pathways were studied by confocal microscopy. In vitro permeation on Franz diffusion cells were performed to determine the rate and extent of drug delivery into and across the skin. SEM captured individual MNs from the array, and the length of each MN was found to be ~400 μm. The 10 × 10 MN array prepared, resulted in the formation of 95 to 100 microchannels after 2 mins of treatment. In addition, the histological evaluations showed the formation of microchannels in the skin, complementary in shape to the MNs. The depths of the formed microchannels amounted to ~125 μm as determined by confocal microscopy. The application of the current MN technology enhanced the delivery of MAP into skin (96.8 ± 3.9 μg/cm2) compared to the passive delivery strategy of MAP (44.9 ± 16.3 μg/cm2). HA MNs markedly enhanced the in vitro transdermal delivery of MAP into and across skin. Keywords Microfabrication . Transdermal drug delivery . Dissolving microneedle . Hydrophilic drug . Hyaluronic acid
1 Introduction Ascorbic acid is an essential vitamin in the skin, which plays an important role in the bio-synthesis of collagen. Recent studies have reported a reduced amount of collagen may affect the skin barrier functions which may cause many skin problems. Also, Kao et al. (1976) showed that collagen synthesis can be promoted by the anti-oxidative capability of ascorbic acid. However, ascorbic acid has limited stability and permeability. Development of ascorbic acid derivatives have been reported to improve the stability of the molecule; however, permeability of the compounds into and across skin were still found to be low (Maia Campos et al. 2012).
* Ajay K. Banga [email protected] 1
Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA
2
MilliporeSigma a Business of Merck KGaA, Frankfurter Strasse 250, 64293 Darmstadt, Germany
Magnesium ascorbyl phosphate (MAP) is a water-soluble derivative of vitamin C (L-Ascorbic acid mono-dihydrogen phosphate magnesium salt), which is more photostable and less suscept
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