Page 61 - IJB-3-2

Roger Sachan, et. al.

deposition approach. This approach also provides s. The hotplate was then turned off during a 3 s pause in
excellent control over coating roughness and coating platform motion. The platform then reversed direction,
homogeneity. Finally, matrix-assisted pulsed laser moving a distance of 1.65 mm at a rate of 1.0 mm/min.
evaporation is a “cold coating process”, since the de- When the platform reversed direction, the microneedle
positing species are not heated. tips were drawn into a more tapered structure. The
Coatings containing several drugs, including gamma- micro needle tips solidified due to the removal of the heat
cyclodextrin/usnic acid and gentamicin sulfate, have source.
been deposited using matrix-assisted pulsed eva-
poration [19–21] . For example, poly(ᴅ,ʟ-lactide)-gentamicin 2.3 Nanoindentation of the Uncoated
com posite coatings that were deposited using matrix- Microneedle
assisted pulsed laser evaporation were shown to possess The hardness and reduced modulus values for the
chemical structures that were similar to those of base of the uncoated microneedle were obtained
[22]
dropcast coatings . In an in vitro study, the gentamicin- using nanoindentation. The microneedle array was
containing coatings were shown to inhibit the growth attached to a magnetic puck with superglue before
of the gram-positive microorganism Staphylococcus the nanoindentation study. The nanoindentation study
aureus. was carried out using a Hysitron Ubi-1 Nanoindenter;
2. Materials and Methods a conical tip was used in this study. Two indentation
studies were conducted with a target maximum load of
2.1 Injection Molding of Microneedle Arrays 500 µN. For each test, a loading time of 20 s, a dwell
time of 10 s at maximum load, and an unloading time of
The microneedle arrays were prepared using Kuredux® 20 s were used. The hardness and reduced modulus were
polyglycolic acid (Kureha, Tokyo, Japan) feedstock as calculated from the unloading curves using the Oliver-
[23]
previously described [11,12] . Pellets of the polyglycolic Pharr approach .
acid material were injection-molded with steel molds
in a Sesame™ molding machine (Trinks Inc., De 2.4 Matrix-Assisted Pulsed Laser Evaporation
Pere, WI, USA) into 1 × 4 microneedle arrays. In the of Amphotericin B
microneedle arrays, the individual microneedles were Solutions containing amphotericin B, polyvinyl-
positioned 1800 µm apart as measured from microneedle pyrrolidone, and dimethyl sulfoxide were mixed at
center to microneedle center. These injection-molded room temperature. Polyvinylpyrrolidone and dimethyl
micro needles were in the form of half-cones on top of sulfoxide are used in topical therapies; for example,
a rectangular base; in this array, the faces of the half- polyvinylpyrrolidone is used in microneedles and di-
cones were aligned with one of the long faces of the methyl sulfoxide is used in topical preparations that are
rectangular substrate in a co-planar manner. used to treat fungal nail infections [24,25] . The solutions

2.2 Use of Drawing Lithography to Sharpen the were prepared by dissolving 1.04 g/mL of amphotericin
Microneedle Tips B or 2.08 g/mL of amphotericin B in dimethyl sulfoxide;
it should be noted that all of the final solutions also
A drawing lithography process was used to sharpen the contained 1 wt% polyvinylpyrrolidone. Prior to each
tips of the injection-molded microneedle arrays [11,12] . deposition, 3.5 mL of the freshly prepared solution was
The microneedles underwent a melt-drawing process, in dropped using a syringe in a copper target holder with
which the microneedle tips were lowered onto a surface a diameter of 3 cm and a height of 5 mm. The solution
that was heated to a temperature of 220 °C. A servomotor converted into solid form, which served as the matrix-
lift platform was used to withdraw the cooling micro- assisted pulsed laser evaporation target by freezing the
needle tips from the stage to create sharp and high solution in liquid nitrogen (77 K) for 30 min. Cryo-
aspect ratio tips. The microneedle arrays were placed genesis was achieved by immersing the target in a
™
above a Cimarec hotplate (Barnstead International, Dewar vessel that was filled with liquid nitrogen. After
Dubuque, IA, USA), which was attached to an AVS125 freezing, the target holder was quickly mounted in the
servomotor lift platform (Aerotech Inc., Pittsburgh, PA, target position inside the matrix-assisted pulsed laser
USA). The microneedle arrays were positioned such evaporation chamber.
that the half-cone axis was oriented toward the hotplate. Amphotericin B coatings were deposited on one-side
When the platform was raised, it made contact with the polished silicon <100> wafer substrates, optic glass
microneedle tips. The stage was paused for 20 s to melt substrates, and polyglycolic acid microneedle arrays.
the microneedle tips; it should be noted that Kuredux® The silicon <100> wafer and optic glass substrates were
polyglycolic acid exhibits a T of 220 °C. The platform ultrasonically cleaned by immersion in ethanol and
m
was raised by a distance of 550 µm at a rate of 0.5 mm/ drying in air. All of the substrates were sterilized prior to
International Journal of Bioprinting (2017)–Volume 3, Issue 2 149