title: Iontophoresis-driven penetration of nanovesicles through microneedle-induced skin microchannels for enhancing transdermal delivery of insulin.
abstract: The transdsermal delivery of insulin remains a significant challenge due to low permeation rates at therapeutically useful rates. We report unilamellar nanovesicles with membrane thickness of 3-5 nm and entrapment efficiency of 89.05+/-0.91%, which can be driven by iontophoresis for enhancing transdermal delivery of insulin through microneedle-induced skin microchannels. The permeation rates of insulin from positive nanovesicles driven by iontophoresis through skins with microneedle-induced microchannels were 713.3 times higher than that of its passive diffusion. The in vivo studies show that the blood glucose levels of diabetic rats induced by the positive nanovesicles driven by iontophoresis through skins with microneedle-induced microchannels are 33.3% and 28.3% of the initial levels at 4 and 6 h, which are comparable to those induced by subcutaneous injection of insulin. The fluorescence imaging validated the penetration of insulin from the nanovesicles driven by iontophoresis through skins with microchannels. The nanovesicles with charges show significant permeation ability with the assistance of physical devices including microneedles and iontophoresis. This approach offers a new strategy for non-invasive delivery of peptides with large molecular weights using nanovesicles.
authors.affiliation: College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
authors.forename: Huabing
authors.initials: H
authors.lastname: Chen
authors.forename: Hongda
authors.initials: H
authors.lastname: Zhu
authors.forename: Jingnan
authors.initials: J
authors.lastname: Zheng
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Mou
authors.forename: Jiangling
authors.initials: J
authors.lastname: Wan
authors.forename: Junyong
authors.initials: J
authors.lastname: Zhang
authors.forename: Tielin
authors.initials: T
authors.lastname: Shi
authors.forename: Yingjun
authors.initials: Y
authors.lastname: Zhao
authors.forename: Huibi
authors.initials: H
authors.lastname: Xu
authors.forename: Xiangliang
authors.initials: X
authors.lastname: Yang
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding; D004563:Electrochemistry; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006168:Guinea Pigs; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007478:Iontophoresis / Q000379:methods*; D008297:Male; D046529:Microscopy, Electron, Transmission; D008970:Molecular Weight; D053758:Nanoparticles; D036103:Nanotechnology; D009339:Needles; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption
chemical_list: D001786:Blood Glucose; D005456:Fluorescent Dyes; D007004:Hypoglycemic Agents; D007328:Insulin; D016650:Fluorescein-5-isothiocyanate