Page 36 - IJB-9-6

International Journal of Bioprinting Transdermal delivery of printed cisplatin

Figure 1. Schematic representation of the LIFT printing process for coating the MNs with cisplatin solution. (A) LIFT setup. (B) Coating process.

water (H 0), and methanol (≥99.8%) were procured from 2.3. MN array fabrication
2
Fisher Scientific (Loughborough, UK). Acetonitrile (ΑCN; Polymethylmethacrylate (PMMA; MW 120k, Sigma-
LC-MS grade) was bought from Carlo Erba (Milan, Italy). Aldrich) was used to create MN arrays as previously
Sodium diethyldithiocarbamate trihydrate (DDTC) was reported by dissolving it at 30 w/v% in ethyl lactate
[31]
obtained from Sigma Aldrich (Sigma-Aldrich Chemie (≥98 %, Sigma-Aldrich) for 1.5 h at 150°C. The 100
GmbH, Munich, Germany). Blank (control) plasma was pyramidal chambers in the MN molds (Micropoint
prepared via centrifugation of whole blood in a Heraeus Technologies) have a base length and height of 200 µm and
Biofuge Pico. Midazolam was kindly provided by Onassis 600 µm, respectively. The MN mold was cast with 50 mg of
Cardiac Surgery Center (Athens, Greece) in the context of 30 w/v% PMMA, which was then centrifuged for 30 min at
a research program in the form of a solution of Dormixal 3500 rpm and allowed to dry overnight in the fume hood.
15 mg/3 mL.
2.4. LIFT process
2.2. Cisplatin solubility The setup used for the LIFT printing of cisplatin solutions
Due to the poor solubility properties of cisplatin in both on MNs is designed for high-speed printing and is presented
H 0 and ethanol (EtOH) , solubility experiments were in Figure 1. The laser source is a DPSS Nd:YAG laser (Sol
[30]
2
performed in distinct solvent mixtures to determine 10W 532 nm, BrightSolutions, Prado PV, Italy) emitting
the optimal solvent system and highest concentration a wavelength of 532 nm with a maximum output power
of the compound that would be compatible with the of 10 W. It delivers pulse duration of around 20 ns, with a
LIFT technology. We initially tested a range of cisplatin repetition rate of 1–100 kHz, respectively, and a Gaussian
concentrations in H 0, achieving a soluble concentration beam profile. The laser beam is scanned with speeds up to
2
of the compound (1 mg/mL). Following that, we checked 3 m/sec by utilizing a 2D galvanometric mirror scanning
cisplatin solubility in a solvent system of 10% glycerol in system (intelliSCAN ΙΙΙ 10, SCANLAB, Puchheim,
H 0, considering glycerol as a compatible reagent with Germany) and an f-theta lens implementing a focal length
2
the LIFT printing process. The solubility of cisplatin in of 100 mm. A beam expander configuration consisting
the 10% glycerol in H 0 solvent system was low (<1 mg/ of a two-lens setup transformed the output laser’s beam
2
mL). Since water mediates displacement of the chloride into the desired 10-mm input size for the galvanometric
atoms in cisplatin (aquation) with unknown effects in the scanning head. After leaving the laser source, the laser
compound’s pharmacological action, we further tested beam travels through the optical setup to determine its
cisplatin solubility in saline and a 10% glycerol in saline size and shape before irradiating a donor substrate that
solvent system, respectively. Since cisplatin was insoluble contains the substance to be deposited. The imaging system
in the glycerol–saline mixture even at 1 mg/mL, saline monitored the whole process in real time via a customized
was opted as the most ideal vehicle for the laser printing microscope system equipped with a camera enabling the
conditions and the in vivo administration. accurate alignment of the target and substrate materials.

Volume 9 Issue 6 (2023) 28 https://doi.org/10.36922/ijb.0048