title: Transdermal delivery of relatively high molecular weight drugs using novel self-dissolving microneedle arrays fabricated from hyaluronic acid and their characteristics and safety after application to the skin.
abstract: The purpose of this study was to develop novel dissolving microneedle arrays fabricated from hyaluronic acid (HA) as a material and to improve the transdermal permeability of relatively high molecular weight drugs. In this study, fluorescein isothiocyanate-labeled dextran with an average molecular weight of 4kDa (FD4) was used as a model drug with a relatively high molecular weight. The microneedle arrays significantly increased transepidermal water loss (TEWL) and reduced transcutaneous electrical resistance (TER), indicating that they could puncture the skin and create drug permeation pathways successfully. Both TEWL and TER almost recovered to baseline levels in the microneedle array group, and relatively small pathways created by the microneedles rapidly recovered as compared with those created by a tape stripping treatment. These findings confirmed that the microneedle arrays were quite safe. Furthermore, we found that the transdermal permeability of FD4 using the microneedle arrays was much higher than that of the FD4 solution. Furthermore, we found that the microneedle arrays were much more effective for increasing the amount of FD4 accumulated in the skin. These findings indicated that using novel microneedle arrays fabricated from HA is a very useful and effective strategy to improve the transdermal delivery of drugs, especially relatively high molecular weight drugs without seriously damaging the skin.
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Shu
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Mei-na
authors.initials: MN
authors.lastname: Jin
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Kyoto, Japan; CosMED Pharmaceutical Co. Ltd., Kyoto, Japan.
authors.forename: Ying-shu
authors.initials: YS
authors.lastname: Quan
authors.affiliation: CosMED Pharmaceutical Co. Ltd., Kyoto, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Kamiyama
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kusamori
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Katsumi
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Sakane
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Kyoto, Japan. Electronic address: yamamoto@mb.kyoto-phu.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Yamamoto
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D003911:Dextrans / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000737:chemistry*; D008845:Microinjections / Q000379:methods; D008970:Molecular Weight; D009339:Needles; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry*; D051381:Rats; D012449:Safety; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption
chemical_list: D003911:Dextrans; D004364:Pharmaceutical Preparations; C015219:fluorescein isothiocyanate dextran; D006820:Hyaluronic Acid; D016650:Fluorescein-5-isothiocyanate
keywords: Absorption enhancement; Barrier disruption; Drug absorption; Hyaluronic acid; Microneedle; Transdermal absorption; Transdermal drug delivery