caa a22 4500 445313676 CHVBK 20180317142638.0 cr unu---uuuuu 170323e20110801xx s 000 0 eng 10.1007/s11095-011-0419-4 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0419-4 Laser-Engineered Dissolving Microneedle Arrays for Transdermal Macromolecular Drug Delivery [Elektronische Daten] [Katarzyna Migalska, Desmond Morrow, Martin Garland, Raj Thakur, A. Woolfson, Ryan Donnelly] ABSTRACT: Purpose: 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. Conclusion: 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. Springer Science+Business Media, LLC, 2011 insulin nationallicence laser engineering nationallicence microneedles nationallicence transdermal drug delivery nationallicence BGL : blood glucose level nationallicence BSA : bovine serum albumin nationallicence CD : circular dichroism nationallicence MN : microneedle nationallicence PMVE/MA : poly(methylvinylether) maleic anhydride nationallicence SC : stratum corneum nationallicence Migalska Katarzyna School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, BT9 7BL, Belfast, UK aut Morrow Desmond School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, BT9 7BL, Belfast, UK aut Garland Martin School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, BT9 7BL, Belfast, UK aut Thakur Raj School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, BT9 7BL, Belfast, UK aut Woolfson A. School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, BT9 7BL, Belfast, UK aut Donnelly Ryan School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, BT9 7BL, Belfast, UK aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/8(2011-08-01), 1919-1930 0724-8741 28:8<1919 2011 28 11095 https://doi.org/10.1007/s11095-011-0419-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0419-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Migalska Katarzyna School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, BT9 7BL, Belfast, UK aut NATIONALLICENCE 700 1- Morrow Desmond School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, BT9 7BL, Belfast, UK aut NATIONALLICENCE 700 1- Garland Martin School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, BT9 7BL, Belfast, UK aut NATIONALLICENCE 700 1- Thakur Raj School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, BT9 7BL, Belfast, UK aut NATIONALLICENCE 700 1- Woolfson A. School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, BT9 7BL, Belfast, UK aut NATIONALLICENCE 700 1- Donnelly Ryan School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, BT9 7BL, Belfast, UK aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/8(2011-08-01), 1919-1930 0724-8741 28:8<1919 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer