A scalable fabrication process of polymer microneedles

Abstract

While polymer microneedles may easily be fabricated by casting a solution in a mold, either centrifugation or vacuumizing is needed to pull the viscous polymer solution into the microholes of the mold. We report a novel process to fabricate polymer microneedles with a one-sided vacuum using a ceramic mold that is breathable but water impermeable. A polymer solution containing polyvinyl alcohol and polysaccharide was cast in a ceramic mold and then pulled into the microholes by a vacuum applied to the opposite side of the mold. After cross-linking and solidification through freeze-thawing, the microneedle patch was detached from the mold and transferred with a specially designed instrument for the drying process, during which the patch shrank evenly to form an array of regular and uniform needles without deformation. Moreover, the shrinkage of the patches helped to reduce the needles' size to ease microfabrication of the male mold. The dried microneedle patches were finally punched to the desired sizes to achieve various properties, including sufficient strength to penetrate skin, microneedles-absorbed water-swelling ratios, and drug-release kinetics. The results showed that the microneedles were strong enough to penetrate pigskin and that their performance was satisfactory in terms of swelling and drug release.

Keywords: ceramic mold; polymer microneedles; polyvinyl alcohol; swelling.

Figure 1

Full view of fabrication process of polymer microneedle patch. The patch was fabricated by casting polymer solution in mold, cross-linking to form needles through freeze-thawing, detaching, and drying.

Figure 2

Fabrication of male mold of microneedles: (A) a single finished hexagonal steel stick; (B) thousands of steel sticks fixed into a steel bucket to form the core of the male mold; (C) the male mold with purple sand spreading smoothly; (D) the female mold prepared using the male mold.

Figure 3

Drying process of microneedle patch. In the first step, the patch was dried with shrinking to adjust size and distance of needles. In the following step, the patch was completely dried with its size fixed.

Figure 4

Siphonage of female molds prepared at different temperatures: (A) 940°C; (B) 980°C; (C) 1020°C.

Figure 5

Instruments used in microneedle-patch drying: (A) stainless plate with six drying units; (B) Teflon board (press 1) over the drying plate; (C) press 2 made of stainless steel with enough weight to fix microneedle patch.

Figure 6

Shrinkage of microneedle patch in free-drying process: (A) effect of relative air humidity; (B) effect of airflow rate.

Figure 7

Skin penetration by microneedles: (A) pigskin dyed with trypan blue after microneedle patch removed; (B) micrograph of tissue slice of the pigskin.

Figure 8

Swelling of microneedles after inserting into human skin: (A) before patching; (B) 1 hour after patching; (C) 3 hours after patching.

Figure 9

In vitro release profile of insulin from microneedle patches to Franz cells (n = 6).