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RESEARCH ARTICLE

           Printing amphotericin B on microneedles using matrix-

           assisted pulsed laser evaporation


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           Roger Sachan , Panupong Jaipan , Jennifer Y. Zhang , Simone Degan , Detlev Erdmann , Jonathan
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           Tedesco , Lyndsi Vanderwal , Shane J. Stafslien , Irina Negut , Anita Visan , Gabriela Dorcioman ,
           Gabriel Socol , Rodica Cristescu , Douglas B. Chrisey  and Roger J. Narayan 2*
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           1  Wake Early College of Health and Sciences, Raleigh, North Carolina, USA
           2  Joint Department of Biomedical Engineering, The University of North Carolina and North Carolina State University,
           Raleigh, North Carolina, USA
           3  Department of Dermatology, Duke University Medical Center, Durham, North Carolina, USA
           4  Department of Surgery, Division of Plastic, Reconstructive, Maxillofacial and Oral Surgery, Duke University Medical
           Center, Durham, North Carolina, USA
           5  Keyence Corporation of America, Elmwood Park, New Jersey, USA
           6  Office of Research and Creativity Activity, North Dakota State University, 1715 Research Park Drive, Fargo ND, USA
           7  National Institute for Lasers, Plasma and Radiation Physics, Lasers Department, P.O. Box MG-36, Bucharest-Magurele,
           Romania
           8  Department of Physics and Engineering Physics, Tulane University, New Orleans, LA, USA
           Abstract: Transdermal delivery of amphotericin B, a pharmacological agent with activity against fungi and parasitic
           protozoa, is a challenge since amphotericin B exhibits poor solubility in aqueous solutions at physiologic pH values. In this
           study, we have used a laser-based printing approach known as matrix-assisted pulsed laser evaporation to print amphotericin
           B on the surfaces of polyglycolic acid microneedles that were prepared using a combination of injection molding and
           drawing lithography. In a modified agar disk diffusion assay, the amphotericin B-loaded microneedles showed concentration-
           dependent activity against the yeast Candida albicans. The results of this study suggest that matrix-assisted pulsed laser
           evaporation may be used to print amphotericin B and other drugs that have complex solubility issues on the surfaces of
           microneedles.
           Keywords: matrix-assisted pulsed laser evaporation, microneedle, amphotericin B, antifungal

           *Correspondence to: Roger J. Narayan, UNC/NCSU Joint Department of Biomedical Engineering, Raleigh, NC 27695-7115, USA;
           Email: roger_narayan@unc.edu
           Received: June 5, 2017; Accepted: July 3, 2017; Published Online: July 14, 2017

           Citation: Sachan R, Jaipan P, Zhang J Y, et al., 2017, Printing amphotericin B on microneedles using matrix-assisted pulsed laser
           evaporation. International Journal of Bioprinting, vol.3(2): 147–157. http://dx.doi.org/10.18063/IJB.2017.02.004.

           1.  Introduction                                    over a prolonged period [1,2] . Anemia, convulsions,
                                                               hypertension, and tremors have also been associated
                 mphotericin B is a “gold standard” for the    with the use of amphotericin B [3–5] . Amphotericin B is
                 sys temic treatment of fungal infections (e.g.,   commonly utilized for the treatment of fungal infections
           ACandida albicans infections) as well as parasitic   despite this significant side-effect profile because it
           protozoal infections [1,2] . This polyene agent interacts with   exhibits the broadest antifungal spectrum, the most
           the ergosterol component of the fungal cell membrane,   potent fungicidal activity, and the least likelihood for
           resulting in increased fungal cell membrane permeability   the generation of antimicrobial resistance among all
           and fungal cell death [3–5] . Amphotericin B exhibits re-  antifungal agents [3–5] .
           nal toxicity; renal failure requiring hemodialysis is   One approach for minimizing the side effects asso-
           associated with the use of amphotericin B at high doses   ciated with the use of amphotericin B for the treat-

           Printing amphotericin B on microneedles using matrix-assisted pulsed laser evaporation. © 2017 Roger Sachan, et al. This is an Open Access article
           distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-
           nc/4.0/), permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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