title: Laser-engineered dissolving microneedle arrays for transdermal macromolecular drug delivery.
abstract: OBJECTIVE
  To assess the feasibility of transdermal macromolecule delivery using novel laser-engineered dissolving microneedles (MNs) prepared from aqueous blends of 20% w/w poly(methylvinylether maleic anhydride) (PMVE/MA) in vitro and in vivo.
  
  
  METHODS
  Micromoulding was employed to prepare insulin-loaded MNs from aqueous blends of 20% w/w PMVE/MA using laser-engineered moulds. To investigate conformational changes in insulin loaded into MNs, circular dichroism spectra were obtained. In vitro drug release studies from MNs across neonatal porcine skin were performed using Franz diffusion cells. The in vivo effect of MNs was assessed by their percutaneous administration to diabetic rats and measurement of blood glucose levels.
  
  
  RESULTS
  MNs loaded with insulin constituted exact counterparts of mould dimensions. Circular dichroism analysis showed that encapsulation of insulin within polymeric matrix did not lead to change in protein secondary structure. In vitro studies revealed significant enhancement in insulin transport across the neonatal porcine skin. Percutaneous administration of insulin-loaded MN arrays to rats resulted in a dose-dependent hypoglycaemic effect.
  
  
  CONCLUSIONS
  We demonstrated the efficacy of MNs prepared from aqueous blends of PMVE/MA in transdermal delivery of insulin. We are currently investigating the fate of the delivered insulin in skin and MN-mediated delivery of other macromolecules.
authors: School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.
authors: Katarzyna
authors: K
authors: Migalska
authors: Desmond I J
authors: DI
authors: Morrow
authors: Martin J
authors: MJ
authors: Garland
authors: Raj
authors: R
authors: Thakur
authors: A David
authors: AD
authors: Woolfson
authors: Ryan F
authors: RF
authors: Donnelly
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D016503:Drug Delivery Systems / Q000295:instrumentation* / Q000379:methods; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D007328:Insulin / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D007834:Lasers; D046911:Macromolecular Substances / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D008297:Male; D008298:Maleates / Q000008:administration & dosage* / Q000737:chemistry*; D008845:Microinjections / Q000295:instrumentation* / Q000379:methods; D009339:Needles; D011095:Polyethylenes / Q000008:administration & dosage* / Q000737:chemistry*; D017433:Protein Structure, Secondary; D051381:Rats; D012869:Skin Absorption; D013552:Swine; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D046911:Macromolecular Substances; D008298:Maleates; D011095:Polyethylenes; C043105:poly(methyl vinyl ether-co-maleic anhydride)