Laser-Induced Forward Transfer Printing on Microneedles for Transdermal Delivery of Gemcitabine

Zoi Kanaki^1†, Chrysoula Chandrinou^2†, Ioanna-Maria Orfanou^1†, Christina Kryou², Jill Ziesmer³, Georgios A. Sotiriou³, Apostolos Klinakis¹, Constantin Tamvakopoulos^1*, Ioanna Zergioti^2*

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¹ Biomedical Research Foundation Academy of Athens, 4 Soranou Ephessiou Street, 11527, Athens, Greece

² Department of Physics, School of Mathematical and Physical Sciences, National Technical University of Athens, Heroon Polytehneiou 9, 15780, Athens, Greece

³ Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77, Stockholm, Sweden

IJB 2022, 8(2), 554 https://doi.org/10.18063/ijb.v8i2.554

Submitted: 28 December 2021 | Accepted: 8 February 2022 | Published: 8 February 2022

© 2022 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )

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Abstract

Cancer treatment with chemotherapeutic drugs remains to be challenging to the physician due to limitations associated with lack of efficacy or high toxicities. Typically, chemotherapeutic drugs are administered intravenously, leading to high drug concentrations that drive efficacy but also lead to known side effects. Delivery of drugs through transdermal microneedles (MNs) has become an important alternative treatment approach. Such delivery options are well suited for chemotherapeutic drugs in which sustained levels would be desirable. In the context of developing a novel approach, laserinduced forward transfer (LIFT) was applied for bioprinting of gemcitabine (Gem) to coat polymethylmethacrylate MNs. Gem, a chemotherapeutic agent used to treat various types of cancer, is a good candidate for MN-assisted transdermal delivery to improve the pharmacokinetics of Gem while reducing efficiency limitations. LIFT bioprinting of Gem for coating of MNs with different drug amounts and successful transdermal delivery in mice is presented in this study. Our approach produced reproducible, accurate, and uniform coatings of the drug on MN arrays, and on in vivo transdermal application of the coated MNs in mice, dose-proportional concentrations of Gem in the plasma of mice was achieved. The developed approach may be extended to several chemotherapeutics and provide advantages for metronomic drug dosing.

Keywords

Laser-induced forward transfer bioprinting

Microneedles

Metronomic chemotherapy

Pharmacokinetics

Transdermal dosing

Sustained drug release

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