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Printing amphotericin B on microneedles using matrix-assisted pulsed laser evaporation

ment of cutaneous fungal infections involves the use In a previous paper, piezoelectric inkjet printing
of transdermal drug delivery devices. Microneedles was used to deposit amphotericin B on the surfaces of
are 50 µm- to 1 mm-long lancet-shaped devices that Gantrez® 169 BF microneedles that were created using
may be used to directly deliver amphotericin B to the a combination with visible light dynamic mask micro-
site of infection [6,7] . These devices are used to create stereolithography and micromolding. The amphotericin
pathways in the keratinized stratum corneum layer of B-loaded microneedles exhibited antifungal activity
the skin, which commonly prevents the movement of against the yeast Candida parapsilosis [11] . It should
[8]
pharmacological agents through the skin . Due to the be noted that coating thickness in piezoelectric inkjet
small dimensions of microneedles, tissue damage at the printing and many other conventional processes is not
treatment site is minimized. Microneedles are associated well controlled; for example, surface wetting may affect
with low levels of pain since they do not penetrate coating thickness [12,13] .
deeper portions of the dermis layer of the skin, where In this paper, we printed amphotericin B onto the
[9]
many large nerve endings are found . surfaces of polyglycolic acid microneedle arrays using
One of the challenges associated with developing matrix-assisted pulsed laser evaporation [14–18] . Matrix-
novel amphotericin B drug delivery methods is that assisted pulsed laser evaporation process involves laser
amphotericin B exhibits poor solubility in aqueous ablation of a frozen target that contains an amount of
solutions at physiological pH values [1,2] . Amphotericin diluted pharmacological agent in a volatile solvent [14–18] .
B exhibits amphipathic behavior because of the apolar The dimethyl sulfoxide solvent is relatively volatile,
and polar components of the lactone ring. Due to its possesses a high vapor pressure, and preferentially
amine and carboxyl groups, amphotericin B exhibits absorbs the laser energy. The dimethyl sulfoxide mo-
amphoteric behavior. As a result of these features, lecules do not deposit on the substrate due to their low
amphotericin B is insoluble in many organic solvents sticking coefficients. The amphotericin B molecules
and aqueous solvents. Several formulations have been at the gas–matrix interface are ejected when kinetic
developed to reduce amphotericin B toxicity, such energy is transferred during collisions with the solvent
as methyl ester and lipid conjugate (e.g., colloidal molecules. The less volatile amphotericin B molecules
dispersion, lipid complex, and liposome) forms [3–5] . For deposit on the substrate and form the vast majority of the
example, several lipid-containing formulations, including coating.
microsphere formulations, nanosphere formulations, Matrix-assisted pulsed laser evaporation enables the
nanoparticle formulations, and nanodisk formulations, thickness of the coating that is printed on the surface
have been developed; these formulations exhibit reduced of the microneedle to be tightly controlled (Figure 1)
renal toxicity [3–5,10] . Unfortunately, many lipid-containing [19] . Matrix-assisted pulsed laser evaporation allows one
formulations are associated with much higher cost than to print a pharmacological agent with precise thick-
conventional amphotericin B delivery methods. ness control since it is a “line-of-sight” physical vapor

Figure 1. Schematic of the matrix-assisted pulsed laser evaporation process . (Reprinted with permission from Elsevier.)
[19]
148 International Journal of Bioprinting (2017)–Volume 3, Issue 2