Development of a Disposable Infusion System for the Delivery of Protein Therapeutics

Abstract

This paper describes the development and optimization of a low flow open-loop infusion device for continuous delivery of protein therapeutics. Specifically, a non-electronic polymer device is actuated with responsive hydrogels to infuse at 2 microL/hr for 12 hours. Hydrogel actuators transduce a chemical signal (change in pH of the local environment) into a mechanical response (swelling) generating the pressure to drive the infusion. The hydrogel actuators are separated from the drug reservoir by an elastomeric impermeable membrane. As the hydrogel actuators expand, the expansion deflects the flexible membrane down and reduces the volume of the drug reservoir causing the infusion of drug through the needle that is the only outlet for the reservoir.

MEMS: Enabled Drug Delivery Systems

“…[ 24 ] Eddington and Beebe developed a disposable infusion system for the delivery of protein therapeutics. [ 34 ] Under specifi c conditions, the pH-responsive hydrogel expands and the drug is expelled from an adjacent reservoir at a rate of 2 µL/h for 12 h. [ 34 ] Chang et al, developed a self-healable chitosan (CS)/ polyvinyl alcohol (PVA) hydrogel for anti-tumor therapy. [ 35 ] This system achieved continuous and controllable drug release at pH 5.0.…”

A hybrid PDMS-Parylene subdural multi-electrode array

“… Sources: (DuPont; Armani et al 1999; Eddington and Beebe 2005; Specialty Coating Systems) * The hybrid layer assumes Parylene and PDMS layers of similar thicknesses …”

“…It is also highly desirable, if possible, to incorporate wireless recording and stimulating systems in close proximity to the electrodes in order to reduce the patient’s hospital stay (in the pre-evaluation epilepsy surgery monitoring) and discomfort (in the case of patients implanted with BCI electronics). PDMS is a known biocompatible material with good mechanical properties for flexible electronics applications (E PDMS ~ 0.360–1.24 MPa; Armani et al 1999; Eddington and Beebe 2005). However, due to its poor adhesion to most metals used in recording and stimulation, it is difficult to embed/deposit electrical interconnects on its surface unless the metallic film is tightly sandwiched between two PDMS layers (Henle et al 2011).…”

A drug delivery system based on alginate microspheres: Mass-transport test and in vitro validation

“…Controlled drug delivery occurs when a polymer, both natural and synthetic, is opportunely combined with a drug or another active agent in such a way that the active agent is released from the material in a designed manner (Dash and Cudworth, 1998;Eddington and Beebe, 2005). The release of the active agent may be constant over a long period, it may be cyclic over a long period, or it may be triggered by the environment or other external events.…”