A self-adherent, bullet-shaped microneedle patch for controlled transdermal delivery of insulin

J Control Release. 2017 Nov 10;265:48-56. doi: 10.1016/j.jconrel.2017.03.041. Epub 2017 Mar 24.

Abstract

Proteins are important biologic therapeutics used for the treatment of various diseases. However, owing to low bioavailability and poor skin permeability, transdermal delivery of protein therapeutics poses a significant challenge. Here, we present a new approach for transdermal protein delivery using bullet-shaped double-layered microneedle (MN) arrays with water-swellable tips. This design enabled the MNs to mechanically interlock with soft tissues by selective distal swelling after skin insertion. Additionally, prolonged release of loaded proteins by passive diffusion through the swollen tips was obtained. The bullet-shaped MNs provided an optimal geometry for mechanical interlocking, thereby achieving significant adhesion strength (~1.6Ncm-2) with rat skin. By harnessing the MN's reversible swelling/deswelling property, insulin, a model protein drug, was loaded in the swellable tips using a mild drop/dry procedure. The insulin-loaded MN patch released 60% of insulin when immersed in saline over the course of 12h and approximately 70% of the released insulin appeared to have preserved structural integrity. An in vivo pilot study showed a prolonged release of insulin from swellable MN patches, leading to a gradual decrease in blood glucose levels. This self-adherent transdermal MN platform can be applied to a variety of protein drugs requiring sustained release kinetics.

Keywords: Insulin delivery; Mechanical interlocking; Microneedle; Transdermal patch.

MeSH terms

  • Acrylates / chemistry*
  • Administration, Cutaneous
  • Animals
  • Biological Availability
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental / drug therapy*
  • Drug Delivery Systems / methods
  • Excipients / chemistry*
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology*
  • Insulin / administration & dosage
  • Insulin / chemistry
  • Insulin / pharmacology*
  • Male
  • Mice, Inbred C57BL
  • Microinjections
  • Needles*
  • Permeability
  • Polystyrenes / chemistry*
  • Rats, Sprague-Dawley
  • Skin / metabolism
  • Skin Absorption
  • Tissue Distribution
  • Transdermal Patch*

Substances

  • Acrylates
  • Blood Glucose
  • Excipients
  • Hypoglycemic Agents
  • Insulin
  • Polystyrenes
  • poly(styrene-b-acrylic acid)