title: Rapidly dissolvable microneedle patches for transdermal delivery of exenatide.
abstract: OBJECTIVE
  To assess the feasibility of transdermal delivery of exenatide (EXT) using low-molecular-weight sodium hyaluronate (HA) dissolving microneedles (MNs) patches for type 2 diabetes mellitus therapy.
  
  
  METHODS
  Micromold casting method was used to fabricate EXT-loaded dissolving MNs. The characteristics of prepared MNs including mechanical strength, in vitro/in vivo insertion capacity, dissolution profile and storage stability were then investigated. Finally, the in vivo pharmacokinetics and hypoglycemic effects were compared with traditional subcutaneous (SC) injection.
  
  
  RESULTS
  EXT-loaded dissolving MNs made of HA possessed sufficient mechanical strength and the strength could be weakened as the water content increases. The EXT preserved its pharmacological activity during fabrication and one-month storage. With the aid of spring-operated applicator, dissolving MNs could be readily penetrated into the skin in vitro/in vivo, and then rapidly dissolved to release encapsulated drug within 2 min. Additionally, transepidermal water loss (TEWL) determinations showed that skin's barrier properties disrupted by MNs recovered within 10-12 h. Transdermal pharmacokinetics and antidiabetic effects studies demonstrated that fabricated EXT MNs induced comparable efficacy to SC injection.
  
  
  CONCLUSIONS
  Our rapidly dissolving MNs patch appears to an excellent, painless alternative to conventional SC injection of EXT, and this minimally invasive device might also be suitable for other biotherapeutics.
authors.affiliation: National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, 1111 Ha Lei Road, Shanghai, 201203, China, zhuzz918@126.com.
authors.forename: Zhuangzhi
authors.initials: Z
authors.lastname: Zhu
authors.forename: Huafei
authors.initials: H
authors.lastname: Luo
authors.forename: Wangding
authors.initials: W
authors.lastname: Lu
authors.forename: Hansen
authors.initials: H
authors.lastname: Luan
authors.forename: Yubo
authors.initials: Y
authors.lastname: Wu
authors.forename: Jing
authors.initials: J
authors.lastname: Luo
authors.forename: Youjie
authors.initials: Y
authors.lastname: Wang
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Pi
authors.forename: Chee Yen
authors.initials: CY
authors.lastname: Lim
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D004355:Drug Stability; D000077270:Exenatide; D005951:Glucose Tolerance Test; D006820:Hyaluronic Acid; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D009339:Needles; D010455:Peptides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D057968:Transdermal Patch; D014688:Venoms / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014870:Water Loss, Insensible
chemical_list: D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D006820:Hyaluronic Acid; D000077270:Exenatide