Magnetically-driven implantable pump for on-demand bolus infusion of short-acting glucagon-like peptide-1 receptor agonist

J Control Release. 2020 Sep 10:325:111-120. doi: 10.1016/j.jconrel.2020.06.022. Epub 2020 Jun 30.

Abstract

For type 2 diabetic patients, short acting glucagon-like peptide-1 receptor agonist (GLP-1 RA) is often prescribed with frequent needled injections. Long-acting GLP-1 RA for less frequent injections do not mimic physiologic secretion of GLP-1. Therefore, an implantable pump is proposed in this work, which can deliver a short-acting GLP-1 RA, exenatide, without needles and batteries. The implanted pump can infuse an accurate amount of exenatide bolus only when a noninvasive magnetic force is applied from outside the body. The pump includes a safety feature of patterned magnets for actuation to prevent accidental infusion possibly caused by a general household magnet. The reservoir for exenatide is made of a flexible biomaterial and thus, a negative pressure build-up in the reservoir can be prevented even after multiple actuations and almost all drug consumption (~ 94%). This allows a reproducible drug dose for a longer period after implantation, hence less frequent replenishment procedures. The pump is also equipped with an intermediate container with two distinct check-valves and thus, the reservoir of exenatide can be further separated and better prevented from infiltration of the bodily fluid surrounding the implanted pump. When tested in Goto-Kakizaki rats, the pump demonstrates the efficacy of exenatide similar to conventional subcutaneous injections. Therefore, the pump can be promising for patient-friendly, optimal delivery of short-acting GLP-1 RA that better follows the physiologic secretion profile of GLP-1.

Keywords: Exenatide; Glucagon-like peptide-1 receptor agonist; Implantable pump; On-demand drug delivery; Type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2*
  • Exenatide / administration & dosage*
  • Glucagon-Like Peptide-1 Receptor / agonists*
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Rats

Substances

  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Exenatide