Journal Article

Laser-Engineered Dissolving Microneedle Arrays for Transdermal Macromolecular Drug Delivery

Garland, Martin J., Donnelly, Ryan F., Morrow, Desmond I. J., Thakur, Raj, Migalska, Katarzyna, Woolfson, A. David

2011

Overview

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.

• Publisher: Springer US,Springer Nature B.V
• Subject: Administration, Cutaneous / Animals / Biochemistry / Biomedical and Life Sciences / Biomedical Engineering and Bioengineering / Biomedicine / Blood / C.D / Diabetes mellitus / Diabetes Mellitus, Experimental - drug therapy / Diabetes Mellitus, Experimental - metabolism / Diffusion / Drug delivery / Drug delivery systems / Drug Delivery Systems - instrumentation / Drug Delivery Systems - methods / Encapsulation / Glucose / Hypoglycemic Agents - administration & dosage / Hypoglycemic Agents - chemistry / Hypoglycemic Agents - pharmacokinetics / Insulin / Insulin - administration & dosage / Insulin - chemistry / Insulin - metabolism / Lasers / Macromolecular Substances - administration & dosage / Macromolecular Substances - chemistry / Macromolecular Substances - pharmacokinetics / Macromolecules / Male / Maleates - administration & dosage / Maleates - chemistry / Manganese / Medical Law / Microinjections - instrumentation / Microinjections - methods / Needles / Neonates / Pharmaceutical sciences / Pharmacology/Toxicology / Pharmacy / Polyethylenes - administration & dosage / Polyethylenes - chemistry / Protein structure / Protein Structure, Secondary / Rats / Research Paper / Secondary structure / Skin / Skin Absorption / Swine / Technology, Pharmaceutical - instrumentation / Technology, Pharmaceutical - methods / Transdermal medication