title: Systemic delivery of artemether by dissolving microneedles.
abstract: Dissolving microneedles (DMNs) based transdermal delivery is an attractive drug delivery approach with minimal invasion. However, it is still challenging to load poorly water-soluble drugs in DMNs for systemic delivery. The aim of the study was to develop DMNs loaded with artemether (ARM) as a model drug, to enable efficient drug penetration through skin for systemic absorption and distribution. The micro-conduits created by microneedles were imaged by confocal laser scanning microscopy (CLSM), and the insertion depth was suggested to be about 270μm. The maximum amount of ARM delivered into skin was 72.67±2.69% of the initial dose loaded on DMNs preparation. Pharmacokinetics study in rats indicated a dose-dependent profile of plasma ARM concentrations, after ARM-loaded DMNs treatment. In contrast to intramuscular injection, DMNs application resulted in lower peak plasma levels, but higher plasma ARM concentration at 8h after administration. There were no significant difference in area under the curve and bioavailability between DMNs group and intramuscular group (P>0.05). Pharmacodynamics studies performed in collagen-induced arthritis (CIA) rats showed that ARM-loaded DMNs could reverse paw edema, similar to ARM intramuscular injection. In conclusion, developed DMNs provided a potential minimally invasive route for systemic delivery of poorly water-soluble drugs.
authors.affiliation: Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.affiliation: Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Suohui
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Guozhong
authors.initials: G
authors.lastname: Yang
authors.affiliation: Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Meilin
authors.initials: M
authors.lastname: He
authors.affiliation: Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, China. Electronic address: yhgao@mail.ipc.ac.cn.
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000077549:Artemether; D037621:Artemisinins / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000295:instrumentation*; D065546:Drug Liberation; D004487:Edema / Q000188:drug therapy; D007273:Injections, Intramuscular; D008297:Male; D008845:Microinjections / Q000295:instrumentation*; D051381:Rats; D012867:Skin / Q000378:metabolism; D013552:Swine
chemical_list: D037621:Artemisinins; D000077549:Artemether
keywords: Artemether; Dissolving microneedles; Intradermal delivery; Poorly water-soluble drugs