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International

                                                                         Journal of Bioprinting



                                        RESEARCH ARTICLE
                                        Printed cisplatin on microneedle arrays for

                                        transdermal delivery enhances olaparib-
                                        induced synthetic lethality in a mouse model of

                                        homologous recombination deficiency



                                        Zoi Kanaki , Alexandra Smina , Chrysoula Chandrinou ,
                                                                                      2
                                                                 1
                                                 1
                                        Fotini E. Koukouzeli , Yiannis Ntounias , Nikolaos Paschalidis , Ilias Cheliotis ,
                                                         1
                                                                                                         2
                                                                                            1
                                                                         1
                                        Marina Makrygianni , Jill Ziesmer , Georgios A. Sotiriou , Ioanna Zergioti ,
                                                                                        3
                                                         2
                                                                     3
                                                                                                       2
                                        Constantin Tamvakopoulos , and Apostolos Klinakis *
                                                               1
                                                                                     1
                                        1 Biomedical Research Foundation Academy of Athens, 4 Soranou Efessiou 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
                                        (This article belongs to the Special Issue: Laser bioprinting technologies)
                                        Abstract
                                        Small molecule inhibitors targeting specific proteins are claiming a continuously
                                        growing share in cancer therapy, more commonly in combination with traditional
                                        chemotherapeutic  drugs.  While  these  inhibitors  are  taken  orally,  the  majority  of
            *Corresponding author:      chemotherapies are administered through intravenous injection in the hospital
            Apostolos Klinakis          premises.  Alternative  routes  for  chemotherapy  administration  would  allow  more
            (aklinakis@bioacademy.gr)
                                        frequent administration at lower dosing by the patient oneself, allowing combination
            Citation: Kanaki Z, Smina A,   treatment with reduced side effects. Here, we employed laser printing to prepare
            Chandrinou C, et al., 2023, Printed
            cisplatin on microneedle arrays   microneedles for transdermal delivery of cisplatin. Combination treatment with
            for transdermal delivery enhances   cisplatin transdermally and the poly (ADP-ribose) polymerase (PARP) inhibitor
            olaparib-induced synthetic lethality   olaparib  orally  leads  to  effective  treatment  in  a  cancer  xenograft  mouse  model
            in a mouse model of homologous
            recombination deficiency.    in vivo, while reducing the risk for systemic side effects. This work opens new avenues
            Int J Bioprint, 9(6): 0048.  in anti-cancer therapy by allowing the administration of chemotherapy without the
            https://doi.org/10.36922/ijb.0048  need for intravenous injection alone or in combination with other therapies.
            Received: February 10, 2023
            Accepted: March 23, 2023
            Published Online: June 23, 2023  Keywords: Laser-induced forward transfer; Microneedles; Metronomic
                                        chemotherapy; Transdermal dosing; Synthetic lethality; Homologous
            Copyright: © 2023 Author(s).
            This is an Open Access article   recombination deficiency
            distributed under the terms of the
            Creative Commons Attribution
            License, permitting distribution,
            and reproduction in any medium,   1. Introduction
            provided the original work is
            properly cited.             Chemotherapy has been the cornerstone of anti-cancer therapy for several decades now.
            Publisher’s Note: AccScience   More  recently,  advances  in  next-generation  sequencing  allowed  the  identification  of
            Publishing remains neutral with   several actionable mutations which can be exploited therapeutically toward personalized
            regard to jurisdictional claims in   approaches in cancer treatment . Novel targeted therapies such as small molecules and
                                                                 [1]
            published maps and institutional
            affiliations.               antibodies that emerged after the 2000s showed great promise and were approved for


            Volume 9 Issue 6 (2023)                         26                        https://doi.org/10.36922/ijb.0048
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