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Drug coated microneedles for minimally-invasive treatment of oral carcinomas: development and in vitro evaluation

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Abstract

Treatment of recurring oral cancers is challenging as common surgical approaches are not feasible for these patients. In addition, these patients do not respond well to systemic chemotherapy. Localized intratumoral injection of anti-cancer drugs is considered to be an attractive alternative treatment approach for these patients. However, conventional hypodermic injections result in poor distribution of the drug in the tumor and leakage of the drug from the injection site to systemic circulation, in addition to causing pain to the patient. The objective of this study was to develop coated microneedles as a novel device for direct and minimally invasive intratumoral delivery of anti-cancer drugs. Poly(lactic-co-glycolic) acid (PLGA) nanoparticles encapsulating doxorubicin (DOX) were prepared and coated on inplane (1D) microneedles. Microscopic evaluation of 3D tissue phantoms and porcine cadaver buccal tissues that were treated with 1D microneedle arrays coated with DOX-PLGA nanoparticles demonstrated that DOX could diffuse both laterally and vertically in to the tissues and produced cellular cytotoxicity. Out of plane (2D) microneedle arrays measuring 1 cm x 1 cm with 57 microneedles coated with free DOX could produce uniform distribution of DOX in a porcine cadaver buccal tissue up to a depth greater than 3 mm. Hypodermic injection of different volumes in to a porcine buccal tissue confirmed significant leakage of the injected volume (about 25 % of the injected 80 μl). In summary, this study demonstrates that drug coated microneedles is an attractive microscale device that can uniformly and effectively deliver drugs to localized oral cancers. This microscale device has potential to impact the treatment of oral cancer patients.

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Acknowledgments

This work was supported in part by the High-Impact/High-Risk Research Award to HSG from the Cancer Prevention and Research Institute of Texas (CPRIT). HSG is a co-inventor on a patent related to microneedle coating technology. The patent application is still pending in the US patent office.

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This potential conflict of interest has been disclosed and is managed by Texas Tech University.

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    Authors and Affiliations

    1. Department of Chemical Engineering, Texas Tech University, 8th Street & Canton Ave, Lubbock, TX, 79409-3121, USA

      Yunzhe Ma, Seth E. Boese & Harvinder S. Gill

    2. Department of Biological and Agricultural Engineering, University of California, Davis, CA, 95616, USA

      Zhen Luo & Nitin Nitin

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    1. Yunzhe Ma
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    2. Seth E. Boese
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    Correspondence to Nitin Nitin or Harvinder S. Gill.

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    Submitted to Biomedical Microdevices for consideration as an Original Research Paper.

    Yunzhe Ma and Seth E. Boese contributed equally to this work.

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    Ma, Y., Boese, S.E., Luo, Z. et al. Drug coated microneedles for minimally-invasive treatment of oral carcinomas: development and in vitro evaluation. Biomed Microdevices 17, 44 (2015). https://doi.org/10.1007/s10544-015-9944-y

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