Effects of hyaluronic acid with different molecular weight on the transdermal absorption of reduced glutathione

TANG Zeyan; GUO Xueping; WEN Ximing; WANG Yuling; LYU Huixia

doi:10.11665/j.issn.1000-5048.20210209

Journal of China Pharmaceutical University > 2021 > 52(2): 203-210. > DOI: 10.11665/j.issn.1000-5048.20210209

TANG Zeyan, GUO Xueping, WEN Ximing, WANG Yuling, LYU Huixia. Effects of hyaluronic acid with different molecular weight on the transdermal absorption of reduced glutathione[J]. Journal of China Pharmaceutical University, 2021, 52(2): 203-210. DOI: 10.11665/j.issn.1000-5048.20210209

Citation:

PDF (1730 KB)

Effects of hyaluronic acid with different molecular weight on the transdermal absorption of reduced glutathione

1.
Department of Pharmacetics, School of Pharmacy, China Pharmaceutical University,Nanjing 211198
2.
Shandong Huaxi Haiyu Biological Medicine Co., Ltd., Ji'nan 250010, China

More Information

Received Date: December 27, 2020
Revised Date: March 15, 2021

Graphical Abstract

Abstract

Abstract

This paper aimed at studying the effects of hyaluronic acid (HA) with different molecular weights on the transdermal absorption and retention of reduced glutathione (GSH) in the isolated skin of SD rats. Franz diffusion cell method was used to investigate the effects with different molecular weights HA on the in vitro transdermal penetration of GSH and the storage in different layers of the skin. AutoDock molecular docking was used to study the interaction between GSH and HA. Attenuated total reflection Fourier transformed infrared spectroscopy (ATR-FTIR) and H&E section staining were used to characterize the changes and effects of lipids and proteins in the rat stratum corneum after HA acts on the skin. The results of in vitro transdermal experiments showed that HA with different molecular weights had a significant impact on the amount of GSH passing through the skin, that as the molecular weight of HA increased, the effect of preventing GSH from passing through the skin became stronger, that in terms of skin storage, HA with different molecular weights could increase the storage of GSH in the stratum corneum, and that HA with a molecular weight below 7K could also significantly increase the storage of GSH in the dermis. The molecular docking results showed that HA and GSH had a relatively strong interaction, which could form intermolecular hydrogen bonds; and the results of ATR-FTIR and H&E staining showed that HA could interact with lipids and keratins in the stratum corneum of the skin. Such interaction can increase the permeability of the stratum corneum of the drug, however, as a water-soluble GSH, it may be involved in the formation of intermolecular hydrogen bonds with HA. In the structure of HA hydrogel, the amount of GSH drug passing through the intact skin is reduced; but at the same time, this interaction also provides a reservoir for the formation of GSH, thus increasing its storage in the skin. Through comparison of the storage capacity of GSH in the stratum corneum and dermis of the isolated skin due to the increase of HA with different molecular weights, it has been found that the storage capacity of HA with low relative molecular weight is the best.

FullText(HTML)

References (27)

References

[1]	.Int J Biol Macromol， 2018， 120（pt b）： 1682-1695.
[2]	Lee YJ， Kim HT， Lee WJ， et al. Anti-aging and hydration efficacy of a cross-linked hyaluronic acid microstructure patch［J］. Dermatol Ther， 2019， 32（3）： e12888.
[3]	Kwon SS， Kong BJ， Park SN. Physicochemical properties of pH-sensitive hydrogels based on hydroxyethyl cellulose-hyaluronic acid and for applications as transdermal delivery systems for skin lesions［J］. Eur J Pharm Biopharm， 2015， 92： 146-154.
[4]	Son SU， Lim JW， Kang T， et al. Hyaluronan-based nanohydrogels as effective carriers for transdermal delivery of lipophilic agents： towards transdermal drug administration in neurological disorders［J］. Nanomaterials， 2017， 7（12）： 427.
[5]	Yue Y， Zhao D， Yin Q. Hyaluronic acid modified nanostructured lipid carriers for transdermal bupivacaine delivery： in vitro and in vivo anesthesia evaluation［J］. Biomed Pharmacother， 2018， 98： 813-820.
[6]	Dilokthornsakul W， Dhippayom T， Dilokthornsakul P. The clinical effect of glutathione on skin color and other related skin conditions： a systematic review［J］. J Cosmet Dermatol， 2019， 18（3）： 728-737.
[7]	Weschawalit S， Thongthip S， Phutrakool P， et al. Glutathione and its antiaging and antimelanogenic effects［J］. Clin Cosmet Investig Dermatol， 2017， 10： 147-153.
[8]	Zhang Y， Ye S. Physiological function and clinical application of reduced glutathione ［J］.Chem Life（生命的化学），2020，40（12）：2226-2235.
[9]	Liang Q， Wang H， Chen K. Research progress on the effects of skin absorption enhancers on the stratum corneum［J］.Centr South Pharm（中南药学）， 2008， 6（4）： 447-450.
[10]	Wang B， Yang W， McKittrick J， et al. Keratin： structure， mechanical properties， occurrence in biological organisms， and efforts at bioinspiration［J］. Prog Mater Sci， 2016， 76： 229-318.
[11]	Lan Y， Wang J， Li H， et al. Effect of menthone and related compounds on skin permeation of drugs with different lipophilicity and molecular organization of stratum corneum lipids［J］. Pharm Dev Technol， 2016， 21（4）： 389-398.
[12]	Zhang S， Song WT， Wu HY， et al. Lecithins-Zein nanoparticles for antifungal treatment： enhancement and prolongation of drug retention in skin with reduced toxicity［J］. Int J Pharm， 2020， 590： 119894.
[13]	Zuo J， Du LN， Li M， et al. Transdermal enhancement effect and mechanism of iontophoresis for non-steroidal anti-inflammatory drugs［J］. Int J Pharm， 2014， 466（1/2）： 76-82.
[14]	Aung NN， Ngawhirunpat T， Rojanarata T， et al. Enhancement of transdermal delivery of resveratrol using Eudragit and polyvinyl pyrrolidone-based dissolving microneedle patches［J］. J Drug Deliv Sci Technol， 2021， 61： 102284.
[15]	Brundu S， Nencioni L， Celestino I， et al. Validation of a reversed-phase high performance liquid chromatography method for the simultaneous analysis of cysteine and reduced glutathione in mouse organs［J］. Oxidative Med Cell Longev， 2016， 2016： 1746985.
[16]	Zou DX， Liu SS， Ke WH， et al. Separation and analysis of thiols by HPLC-UV with pre-column derivatization［J］. Guangdong Chem Ind（广东化工）， 2019， 46（16）： 4-6.
[17]	Abe A， Saito M， Kadhum WR， et al. Establishment of an evaluation method to detect drug distribution in hair follicles［J］. Int J Pharm， 2018， 542（1/2）： 27-35.
[18]	Hoppel M， Baurecht D， Holper E， et al. Validation of the combined ATR-FTIR/tape stripping technique for monitoring the distribution of surfactants in the stratum corneum［J］. Int J Pharm， 2014， 472（1/2）： 88-93.
[19]	Wolf M， Halper M， Pribyl R， et al. Distribution of phospholipid based formulations in the skin investigated by combined ATR-FTIR and tape stripping experiments［J］. Int J Pharm， 2017， 519（1/2）： 198-205.
[20]	Binder L， Kulovits EM， Petz R， et al. Penetration monitoring of drugs and additives by ATR-FTIR spectroscopy/tape stripping and confocal Raman spectroscopy－a comparative study［J］. Eur J Pharm Biopharm， 2018， 130： 214-223.
[21]	Kobayashi Y， Okamoto A， Nishinari K. Viscoelasticity of hyaluronic acid with different molecular weights［J］. Biorheology， 1994， 31（3）： 235-244.
[22]	Witting M， Boreham A， Brodwolf R， et al. Interactions of hyaluronic acid with the skin and implications for the dermal delivery of biomacromolecules［J］. Mol Pharm， 2015， 12（5）： 1391-1401.
[23]	Zhang Y， Xia Q， Li Y， et al.CD44 assists the topical anti-psoriatic efficacy of curcumin-loaded hyaluronan-modified ethosomes： a new strategy for clustering drug in inflammatory skin［J］. Theranostics， 2019， 9（1）： 48-64.
[24]	Nashchekina YA， Raydan M. Noninvasive penetration of 5 nm hyaluronic acid molecules across the epidermal barrier （in vitro） and its interaction with human skin cells［J］. Skin Res Technol， 2018， 24（1）： 129-134.
[25]	Kim H， Lee S， Ki CS. Modular formation of hyaluronic acid/β-glucan hybrid nanogels for topical dermal delivery targeting skin dendritic cells［J］. Carbohydr Polym， 2021， 252： 117132.
[26]	Farwick M， Gauglitz G， Pavicic T， et al. Fifty-kDa hyaluronic acid upregulates some epidermal genes without changing TNF-α expression in reconstituted epidermis［J］. Skin Pharmacol Physiol， 2011， 24（4）： 210-217.
[27]	Farwick M， Lersch P， Strutz G. Low molecular weight hyaluronic acid： its effects on epidermal gene expression & skin ageing［J］. S?FW J， 2008， 134（11）： 17.

Cited By

Get Citation

PDF

XML

Article views (381) PDF downloads (965)

Turn off MathJax

Article Contents

Abstract

References

Effects of hyaluronic acid with different molecular weight on the transdermal absorption of reduced glutathione

Abstract

References

Catalog

Export File

Citation

Format

Content