Micromolding of Amphotericin-B-Loaded Methoxyethylene-Maleic Anhydride Copolymer Microneedles

Abstract

Biocompatible and biodegradable materials have been used for fabricating polymeric microneedles to deliver therapeutic drug molecules through the skin. Microneedles have advantages over other drug delivery methods, such as low manufacturing cost, controlled drug release, and the reduction or absence of pain. The study examined the delivery of amphotericin B, an antifungal agent, using microneedles that were fabricated using a micromolding technique. The microneedle matrix was made from Gantrez^TM AN-119 BF, a benzene-free methyl vinyl ether/maleic anhydride copolymer. The Gantrez^TM AN-119 BF was mixed with water; after water evaporation, the polymer exhibited sufficient strength for microneedle fabrication. Molds cured at room temperature remained sharp and straight. SEM images showed straight and sharp needle tips; a confocal microscope was used to determine the height and tip diameter for the microneedles. Nanoindentation was used to obtain the hardness and Young's modulus values of the polymer. Load-displacement testing was used to assess the failure force of the needles under compressive loading. These two mechanical tests confirmed the mechanical properties of the needles. In vitro studies validated the presence of amphotericin B in the needles and the antifungal properties of the needles. Amphotericin B Gantrez^TM microneedles fabricated in this study showed appropriate characteristics for clinical translation in terms of mechanical properties, sharpness, and antifungal properties.

Keywords: amphotericin B; fungus; microneedles; transdermal drug delivery.

Figure 1

Scanning electron microscope image of amphotercin B–Gantrez^TM microneedles with buckled tips.

Figure 2

Scanning electron microscope image of 8% amphotericin B–Gantrez^TM microneedles.

Figure 3

Scanning electron microscope image of 4% amphotericin B–Gantrez^TM microneedles.

Figure 4

The load per time diagram of ElectroForce^® compression testing of a microneedle; point (1) reveals when the needle tips break.

Figure 5

Keyence imaging results for (A) 4% amphotericin-B-loaded Gantrez^TM microneedles and (B) 8% amphotericin-B-loaded Gantrez^TM microneedles. The red lines represent measurements of the microneedle dimensions. Measurement [1] represents microneedle height, measurement [2] represents the microneedle base diameter, and measurement [3] represents microneedle tip diameter.

Figure 6

FTIR spectra from (A) 4% amphotericin B-loaded microneedles, and (B) 8% amphotericin B-loaded microneedles.

Figure 6

FTIR spectra from (A) 4% amphotericin B-loaded microneedles, and (B) 8% amphotericin B-loaded microneedles.

Figure 7

XPS spectrum of the combination of Gantrez^TM AN-119 BF and amphotericin B.

Figure 8

Raman spectrum of Gantrez^TM/amphotericin B (top), amphotericin B (center), and Gantrez^TM (bottom).

Figure 9

Modified disk diffusion assay results involving Candida albicans for 8% and 0% amphotericin-B-loaded Gantrez^TM microneedles; (A) partially solvated microneedles; (B) fully solvated microneedles. ZOI = zone of inhibition.

Figure 10

Candida albicans solution growth assessments in nutrient media dilutions of fully solvated microneedles. The 100% concentration denotes microneedle samples solvated in 3 mL of PBS (1×).