Pharmaceutical research · 2011
Laser-engineered dissolving microneedle arrays for transdermal macromolecular drug delivery.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Migalska Katarzyna, Morrow Desmond I J, Garland Martin J, Thakur Raj, Woolfson A David, Donnelly Ryan F
Аннотация
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.
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.