title: Assembled microneedle arrays enhance the transport of compounds varying over a large range of molecular weight across human dermatomed skin.
abstract: In this study, we demonstrate the feasibility to use microneedle arrays manufactured from commercially available 30G hypodermal needles to enhance the transport of compounds up to a molecular weight of 72 kDa. Piercing of human dermatomed skin with microneedle arrays was studied by Trypan Blue staining on the SC side of the skin and transepidermal water loss measurements (TEWL). Passive transport studies were conducted with Cascade Blue (CB, Mw 538), Dextran-Cascade Blue (DCB, Mw 10 kDa), and FITC coupled Dextran (FITC-Dex, Mw 72 kDa). Microneedle arrays with needle lengths of 900, 700 and 550 micro m are able to pierce dermatomed human skin as evident from (a) the appearance of blue spots on the dermal side of the skin after Trypan Blue treatment and (b) elevated TEWL levels after piercing compared to non-treated human dermatomed skin. Microneedles with a length of 300 micro m did not pierce human skin in vitro. Transport studies performed with model compounds ranging from 538 Da to 72 kDa revealed that pretreatment with microneedle arrays enhanced the transport across dermatomed human skin. However, some degradation was also observed for FITC-Dex and DCB. We conclude that assembled microneedle arrays can be used to deliver compounds through the skin up to a molecular weight of at least 72 kDa.
authors.affiliation: Department of Drug Delivery Technology, Leiden/Amsterdam Center for Drug Research, 2300 RA, Leiden, The Netherlands.
authors.forename: F J
authors.initials: FJ
authors.lastname: Verbaan
authors.forename: S M
authors.initials: SM
authors.lastname: Bal
authors.forename: D J
authors.initials: DJ
authors.lastname: van den Berg
authors.forename: W H H
authors.initials: WH
authors.lastname: Groenink
authors.forename: H
authors.initials: H
authors.lastname: Verpoorten
authors.forename: R
authors.initials: R
authors.lastname: Lüttge
authors.forename: J A
authors.initials: JA
authors.lastname: Bouwstra
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D003911:Dextrans / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D066298:In Vitro Techniques; D008845:Microinjections / Q000295:instrumentation*; D008970:Molecular Weight; D009339:Needles; D009942:Organometallic Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000378:metabolism; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D014343:Trypan Blue / Q000737:chemistry / Q000493:pharmacokinetics; D014867:Water / Q000378:metabolism
chemical_list: D003911:Dextrans; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D004364:Pharmaceutical Preparations; C015219:fluorescein isothiocyanate dextran; D014867:Water; C066850:Cascade Blue; D016650:Fluorescein-5-isothiocyanate; D014343:Trypan Blue