In Vivo Experimental Study of Noninvasive Insulin Microinjection through Hollow Si Microneedle Array.

Drago Resnik,Ciprian Iliescu,Andrej Janež,Borut Pečar,Matej Možek,Danilo Vrtačnik,Vilma Urbančič

doi:10.3390/mi9010040

Abstract

An experimental study of in vivo insulin delivery through microinjection by using hollow silicon microneedle array is presented. A case study was carried out on a healthy human subject in vivo to determine the influence of delivery parameters on drug transfer efficiency. As a microinjection device, a hollow microneedle array (13 × 13 mm2) having 100 microneedles (220 µm high, 130 µm-outer diameter and 50 µm-inner diameter) was designed and fabricated using classical microfabrication techniques. The efficiency of the delivery process was first characterized using methylene blue and a saline solution. Based on these results, the transfer efficiency was found to be predominantly limited by the inability of viable epidermis to absorb and allow higher drug transport toward the capillary-rich region. Two types of fast-acting insulin were used to provide evidence of efficient delivery by hollow MNA to a human subject. By performing blood analyses, infusion of more-concentrated insulin (200 IU/mL, international units (IU)) exhibited similar blood glucose level drop (5–7%) compared to insulin of standard concentration (100 IU/mL), however, significant increase of serum insulin (40–50%) with respect to the preinfusion values was determined. This was additionally confirmed by a distinctive increase of insulin to C-peptide ratio as compared to preinfusion ratio. Moreover, we noticed that this route of administration mimics a multiple dose regimen, able to get a “steady state” for insulin plasma concentration.

Highlights

Transdermal drug delivery (TDD) is an attractive alternative to subcutaneous route of delivery for various drugs and vaccines, but usually limited by the extremely low permeability of the outer skin layer, a 10–15 μm thick stratum corneum (SC)
In order to optically determine the uniformity of liquid flow through an array of 100 microneedles and to detect the eventual failure sites, preliminary tests were performed with methylene blue (MB) dye
In order to optically determine the uniformity of liquid flow through an array of 100 microneedles and to detect the eventual failure sites, preliminary tests were performed with MB dye delivery into the human skin,arm often used for used microneedle penetration studies [23,39]

Summary

Introduction

Transdermal drug delivery (TDD) is an attractive alternative to subcutaneous route of delivery for various drugs and vaccines, but usually limited by the extremely low permeability of the outer skin layer, a 10–15 μm thick stratum corneum (SC). Microneedle arrays (MNA) have shown immense potential to effectively deliver drugs intradermally and transdermally, when a relatively small volume of drug is required [1,2]. The advantages and disadvantages of the transdermal route for drug delivery by using microneedles have been thoroughly presented and discussed in numerous review papers [3,4,5,6,7,8]. Different strategies to facilitate this delivery route were developed and proposed [3,9,10,11,12,13]. In this direction two main categories of MNA were developed: solid MNA and hollow MNA.

Methods

Results

Discussion

Conclusion