Hyaluronan-Based Nanohydrogels as Effective Carriers for Transdermal Delivery of Lipophilic Agents: Towards Transdermal Drug Administration in Neurological Disorders.

Seong Son,Eun-Kyung Lim,Taejoon Kang,Jae-Woo Lim,Juyeon Jung

doi:10.3390/nano7120427

Abstract

We suggest a convenient nanoemulsion fabrication method to create hyaluronan (HA)-based nanohydrogels for effective transdermal delivery. First, hyaluronan-conjugated dodecylamine (HA–Do) HA-based polymers to load the lipophilic agents were synthesized with hyaluronan (HA) and dodecylamine (Do) by varying the substitution ratio of Do to HA. The synthetic yield of HA–Do was more than 80% (HA–Do (A): 82.7 ± 4.7%, HA–Do (B): 87.1 ± 3.9% and HA–Do (C): 81.4 ± 4.5%). Subsequently, nanohydrogels were fabricated using the nanoemulsion method. Indocyanine green (ICG) simultaneously self-assembled with HA–Do, and the size depended on the substitution ratio of Do in HA–Do (nanohydrogel (A): 118.0 ± 2.2 nm, nanohydrogel (B): 121.9 ± 11.4 nm, and nanohydrogel (C): 142.2 ± 3.8 nm). The nanohydrogels were delivered into cells, and had excellent biocompatibility. Especially, nanohydrogel (A) could deliver and permeate ICG into the deep skin layer, the dermis. This suggests that nanohydrogels can be potent transdermal delivery systems.

Highlights

Skin is the major organ of the human body, and it forms a barrier between the body and the outside environment [1,2]
As the feed ratio of Do in hyaluronan-conjugated dodecylamine (HA–Do) increased, the critical micelle cnoanncoenhtyrdartioognel(sCpMreCp)adreedcrueassinedg,ddifufeerteonsttfreoendgrearthioysdorfoDphootboicHiAntewraasctmioenassiunrethdeucsoinregdlausreirnsgcmatticeerilnleg f(oTrambaletio2)n..ALsikweewpirseev, itohuesslyizreeopforthteedn, aasnothheyfdereodgeralstidoeocfrDeaoseind HasAt–hDeofeiendcrreaatsieodo, fthDeocriinticcraelamseidceilnle HcoAn–cDeon,trbaetciaouns(eCoMf tCh)edenechraenacseemd,ednut ienttohsetrhoyndgroerphhoybdircoipnhteorbaicctiionntesrbaecttwioenesnitnhtehDeocogrreoudpusriinngHmAi–cDelole afnodrmlipatoipohni.lLicikmeawteisreia, ltsh(eTsaibzleeo2f).thOevnearanlol,htyhdersoizgeelosfdthecerneaanseodhyads rtohgeeflesewdarsatlieossotfhDaon i2n0c0renamse, danind HwAill– hDelop, pbeencaeutrsaeteodf etheepeernlhaaynecrsemofetnhteinsktihne
HA–Do was synthesized by varying the substitution ratio of Do to HA, and the synthetic yield was more than 80%

Summary

Introduction

Skin is the major organ of the human body, and it forms a barrier between the body and the outside environment [1,2]. The skin barrier can be open and permeable to the environment to allow the exchange of heat, air, and fluids containing very low molecular weight molecules [1]. This provides an alternative route for drug administration, i.e., transdermal drug delivery into the blood circulation, and provides greater comfort to the patient compared with oral and parenteral administration [6,7]. Microneedle patches with an array of micron-scale needles create holes in the SC for skin permeability dNiaffniocmualtteireiasls, 2v01a7r,i7o,u42s7 transdermal drug delivery systems have been developed [5–7,10–13].2. Fofo1r1 instance, microneedle patches with an array of micron-scale needles create holes in the SC for skin permeability enhancement [14]. HicaAllycanropbruosdtumceatmereicahlsanbicyallcyheamndicachl emmoicdailfliycartoiobnustwmhialteermiaalsinbtyainchinegmiictasl bmioocdoimficpaattioibniliwtyhailnedmbaiiondtaeignriandgabitislitbyio[c1o9m,25p,a2t6ib].ilMityoraenrdecbeinotdlyeg, rHaAdaabnildityH[A19d,2e5r,2iv6a].tivMesohreavreecbeenetnly, sHucAceasnsdfuHllAy ddeevrievlaotpiveeds ahnavdeubseeednassuctcoepsiscfaull,lyimdpevlaenlotpabedlea(nodr uinsjeedctaasbtloe)pivceahl,iicmlepsla(en.tga.b, lnea(noor pinajretcitcalbelse,) hvyedhricolgesel(se,.agn.,dnasncaofpfoarldtisc)lefso,rhcyodnrtorgoelllesd, a, nlodcascliazfefodlddse)lifvoerrcyoonftrboilolelodg, ilcoaclallyizoerdpdhealrivmearycoolfobgiioclaolglyicaaclltyivoer mphoalercmualecosltoogtichaellsykaincti[v1e2,m27o–l4e1cu].les to the skin [12,27–41]

Methods

Results

Conclusion