Hollow Metal Microneedles for Insulin Delivery to Diabetic Rats

Abstract

The goal of this study was to design, fabricate, and test arrays of hollow microneedles for minimally invasive and continuous delivery of insulin in vivo. As a simple, robust fabrication method suitable for inexpensive mass production, we developed a modified-LIGA process to micromachine molds out of polyethylene terephthalate using an ultraviolet laser, coated those molds with nickel by electrodepostion onto a sputter-deposited seed layer, and released the resulting metal microneedle arrays by selectively etching the polymer mold. Mechanical testing showed that these microneedles were sufficiently strong to pierce living skin without breaking. Arrays containing 16 microneedles measuring 500 microm in length with a 75 microm tip diameter were then inserted into the skin of anesthetized, diabetic, hairless rats. Insulin delivery through microneedles caused blood glucose levels to drop steadily to 47% of pretreatment values over a 4-h insulin delivery period and were then approximately constant over a 4-h postdelivery monitoring period. Direct measurement of plasma insulin levels showed a peak value of 0.43 ng/ml. Together, these data suggest that microneedles can be fabricated and used for in vivo insulin delivery.

Transdermal drug delivery by coated microneedles: geometry effects on drug concentration in blood

“…[8,9] This paper has focused on modelling insulin delivery from a microneedle system. Insulin delivery is needed for various medical reasons such as lowering the blood glucose levels in the treatment of diabetes, [10] reducing the infarct size and hence improving 60 the diagnosis of the patient once the stroke occurred, [11] etc. In fact, insulin has been adopted as a model drug in many studies for transdermal drug delivery using microneedles.…”

“…In fact, insulin has been adopted as a model drug in many studies for transdermal drug delivery using microneedles. [10,[12][13][14][15] We choose insulin as a model drug for the purposes of this paper.…”

Laser micro- and nanofabrication of biomaterials

“…113 Davis et al created 500 μ m long hollow metal microneedles from polyethylene terephthalate molds; these molds contained holes that were drilled using a 248 nm ultraviolet laser. 114 Molds containing straight-walled holes were used to create cylindrical tubes; molds containing tapered holes were used to create conical microneedles. The molds were subsequently coated with nickel using an electroplating process that used direct-current sputtered titaniumcopper-titanium as a seed layer.…”

Toward Self‐Powered Wearable Adhesive Skin Patch with Bendable Microneedle Array for Transdermal Drug Delivery

“…It can alert patients and provide the guidance when the dose of the drug to be delivered should be accurately controlled 47, 48, 49, 50. Currently, several wearable sensors for health monitoring have been explored, including devices that measure hydration,51 strain,52 glycaemia,53, 54, 55 metabolic acid,56 and cardiorespiratory signals 53.…”