Development of vertical SU-8 microtubes integrated with dissolvable tips for transdermal drug delivery

Abstract

Polymer-based microneedles have drawn much attention in the transdermal drug delivery resulting from their flexibility and biocompatibility. Traditional fabrication approach deploys various kinds of molds to create sharp tips at the end of needles for the penetration purpose. This approach is usually time-consuming and expensive. In this study, we developed an innovative fabrication process to make biocompatible SU-8 microtubes integrated with biodissolvable maltose tips as novel microneedles for the transdermal drug delivery applications. These microneedles can easily penetrate the skin's outer barrier represented by the stratum corneum (SC) layer. The drug delivery device of mironeedles array with 1000 μm spacing between adjacent microneedles is proven to be able to penetrate porcine cadaver skins successfully. The maximum loading force on the individual microneedle can be as large as 7.36 ± 0.48N. After 9 min of the penetration, all the maltose tips are dissolved in the tissue. Drugs can be further delivered via these open biocompatible SU-8 microtubes in a continuous flow manner. The permeation patterns caused by the solution containing Rhodamine 110 at different depths from skin surface were characterized via a confocal microscope. It shows successful implementation of the microneedle function for fabricated devices.

Figure 1

Schematic illustration of the SU-8 microneedles. (a) Top view of the device structure. (b) A 5×5 SU-8 microneedles array. (c) Cross section of the device structure. (d) Single microneedle structure.

Figure 2

Fabrication process for SU-8 microtubes.

Figure 3

(a) Schematic illustration of the homemade stage to ensure flat SU-8 membrane surface. (b) SU-8 membrane bends after development. (c) After bonded with PDMS and clamped in the stage, the membrane becomes flat.

Figure 4

Fabrication process for maltose tips. (a) Expelling water at 140 °C. (b) Immersing microtubes into the maltose at 140 °C. (c) Drawing the tips at end of the microtubes when the temperature increases up to 160 °C. (d) Increasing drawing speed to form sharp tips.

Figure 5

(a) Optical image for the finished SU-8 microneedles. (b) Detailed illustration image for the microneedles array.

Figure 6

(a) Testing setup for the microneedle mechanical testing. (b) A typical microneedle stiffness testing result.

Figure 7

Penetration testing results on the porcine cadaver skin.

Figure 8

Maltose tips dissolving process. (a) The original sharp maltose tip. (b) Maltose tip after inserted into skin for 3 min. (c) Maltose tip after inserted into skin for 6 min. (d) Maltose tip after inserted into skin for 9 min.

Figure 9

Images of confocal microscopy of the site where one microneedle inserted shows that the fluorescent solution is delivered into the tissue underneath the skin surface. Optical section depths are (a) 30 μm, (b) 60 μm, (c) 90 μm, (d) 120 μm, (e) 150 μm, and (f) 180 μm below the skin surface.