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RESEARCH ARTICLE

Laser-Induced Forward Transfer Printing on

Microneedles for Transdermal Delivery of Gemcitabine

Zoi Kanaki , Chrysoula Chandrinou , Ioanna-Maria Orfanou , Christina Kryou , Jill Ziesmer ,
2†
1†
3
1†
2
Georgios A. Sotiriou , Apostolos Klinakis , Constantin Tamvakopoulos *, Ioanna Zergioti *
1
3
1
2
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
† These authors contributed equally to this work.
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, laser-
induced 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
*Correspondence to: Ioanna Zergioti, National Technical University of Athens, Athens GR15780, zergioti@central.ntua.gr; Constantin
Tamvakopoulos, Biomedical Research Foundation Academy of Athens, Athens, GR 11527; ctamvakop@bioacademy.gr
Received: December 28, 2021; Accepted: February 8, 2022; Published Online: February 8, 2022

Citation: Kanaki Z, Chandrinou C, Orfanou IM, et al., 2022, Laser Induced Forward Transfer Printing on Microneedles for Transdermal
Delivery of Gemcitabine. Int J Bioprint, 8(2):554. http://doi.org/10.18063/ijb.v8i2.554

1. Introduction API-entrapped in soluble MNs [3-6] (b) API-coated MNs ,
[7]
(c) API applied on a patch after the skin has been pierced
In the past decades, drug delivery through microneedles [8]
(MNs) has become an important approach for treatment by solid MNs , (d) hollow MNs that enable a continuous
when compared to other transdermal methods such as fluid flow of the API, and (e) swelling MNs which swell
hypodermic needles, topical creams, and transdermal after application and absorption of interstitial fluid, leading
[9]
patches. MNs have several advantages over the to drug diffusion through the swollen MNs . API-coated
aforementioned methods such as deeper skin penetration, MNs can be used for delivery of both hydrophilic and
reduced pain, and increased penetration of high molecular hydrophobic drugs [5,10,11] . Their ideal use is for low-dose
weight drug molecules through stratum corneum, the administration of potent drugs, which are efficacious at
skin’s outermost layer. There are five main ways for low circulating amounts. For example, vaccines applied
active pharmaceutical ingredient (API) delivery [1,2] : (a) with MNs induce similar or better immune responses when

© 2022 Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution License, permitting distribution and
reproduction in any medium, provided the original work is properly cited.
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