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A multilayered sheet-type device capable of sustained drug release and deployment control

Biomedical Microdevices volume 21, Article number: 60 (2019) Cite this article

Abstract

Minimally invasive delivery of a sustained drug release device to the body is a promising approach for treating chronic conditions such as retinal diseases. Herein, we describe a sheet-type device capable of sustained drug release and deployment control after being applied to the body through a small opened hole via a syringe-type injector. Such device consists of a four-layered structure of thin photopolymerized sheets, which are in turn made of different ratios of a mixture of polyethylene glycol dimethacrylate (PEGDM) and triethylene glycol dimethacrylate (TEGDM). A layer containing a model drug, i.e., fluorescein, was sandwiched between a controlled release and guard layer to achieve sustained unidirectional drug release. A deployment layer was then attached onto the guard layer to control the curvature of the device following deployment. The sheet-type device was sufficiently flexible to be rolled up and could be inserted into a syringe-type injector. When the device was injected into the subconjunctival space of a rabbit eye through a small opened hole, it unfolded to fit the eyeball curvature. Moreover, homogenates of the choroid/retinal pigment epithelium (RPE) as well as the retina exhibited fluorescence during 4 weeks after implantation, confirming that the drug could be delivered to the retina by using the device. This developed sheet-type device offers the possibility of achieving minimally invasive transplantation into diseased tissues and organs, and could provide improved therapeutic modalities as well as reduce possible side effects.

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References

  • J. Ambati, A.P. Adamis, Prog. Retin. Eye Res. 21, 145 (2002)

    Article  Google Scholar 

  • P. Bansal, S. Garg, Y. Sharma, P. Venkatesh, J. Ocul. Pharmacol. Ther. 32, 135 (2016)

    Article  Google Scholar 

  • S. Duvvuri, S. Majumdar, A.K. Mitra, Expert Opin. Biol. Ther. 3, 45 (2003)

    Article  Google Scholar 

  • D.H. Geroski, H.F. Edelhauser, Adv. Drug Deliv. Rev. 52, 37 (2001)

    Article  Google Scholar 

  • P.M. Hughes, O. Olejnik, J.E. Chang-Lin, C.G. Wilson, Adv. Drug Deliv. Rev. 57, 2010 (2005)

    Article  Google Scholar 

  • H. Kaji, N. Nagai, M. Nishizawa, T. Abe, Adv. Drug Deliv. Rev. 128, 148 (2018)

    Article  Google Scholar 

  • T. Kawashima, N. Nagai, H. Kaji, N. Kumasaka, H. Onami, Y. Ishikawa, N. Osumi, M. Nishizawa, T. Abe, Biomaterials 32, 1950 (2011)

    Article  Google Scholar 

  • S.H. Kim, R.J. Lutz, N.S. Wang, M.R. Robinson, Ophthalmic Res. 39, 244 (2007)

    Article  Google Scholar 

  • Y.C. Kim, B. Chiang, X.G. Wu, M.R. Prausnitz, J. Control. Release 190, 172 (2014)

    Article  Google Scholar 

  • T. Kondo, Z.K. Nezhad, J. Suzuki, N. Nagai, M. Nishizawa, T. Abe, H. Kaji, J. Biomed. Mater. Res. Part B 106, 780 (2018)

    Article  Google Scholar 

  • N. Nagai, H. Kaji, H. Onami, Y. Ishikawa, M. Nishizawa, N. Osumi, T. Nakazawa, T. Abe, Acta Biomater. 10, 680 (2014a)

    Article  Google Scholar 

  • N. Nagai, H. Kaji, H. Onami, Y. Katsukura, Y. Ishikawa, Z.K. Nezhad, K. Sampei, S. Iwata, S. Ito, M. Nishizawa, T. Nakazawa, N. Osumi, Y. Mashima, T. Abe, Adv. Healthc. Mater. 3, 1555 (2014b)

    Article  Google Scholar 

  • N. Nagai, S. Iwata, H. Kaji, K. Sampei, Y. Katsukura, H. Onami, M. Nishizawa, T. Nakazawa, Y. Mashima, T. Abe, J. Biomed. Mater. Res. Part B 104, 1730 (2016a)

    Article  Google Scholar 

  • N. Nagai, H. Kaji, M. Nishizawa, T. Nakazawa, T. Abe, Adv. Exp. Med. Biol. 854, 471 (2016b)

    Article  Google Scholar 

  • N. Nagai, E. Koyanagi, Y. Izumida, J. Liu, A. Katsuyama, H. Kaji, M. Nishizawa, N. Osumi, M. Kondo, H. Terasaki, Y. Mashima, T. Nakazawa, T. Abe, Invest. Ophthalmol. Vis. Sci. 57, 6527 (2016c)

    Article  Google Scholar 

  • Z.K. Nezhad, N. Nagai, K. Yamamoto, H. Kaji, M. Nishizawa, H. Saya, T. Nakazawa, T. Abe, J. Mater. Sci. Mater. Med. 26, 230 (2015)

    Article  Google Scholar 

  • H. Onami, N. Nagai, H. Kaji, M. Nishizawa, Y. Sato, N. Osumi, T. Nakazawa, T. Abe, PLoS One 8, e58580 (2013)

    Article  Google Scholar 

  • S. Raghava, M. Hammond, U.B. Kompella, Expert Opin. Drug Deliv. 1, 99 (2004)

    Article  Google Scholar 

  • V.P. Ranta, A. Urtti, Adv. Drug Deliv. Rev. 58, 1164 (2006)

    Article  Google Scholar 

  • V.P. Ranta, E. Mannermaa, K. Lummepuro, A. Subrizi, A. Laukkanen, M. Antopolsky, L. Murtomaki, M. Hornof, A. Urtti, J. Control. Release 148, 42 (2010)

    Article  Google Scholar 

  • S. Shimbo, T. Fujie, E. Iwase, Jpn. J. Appl. Phys. 55, 06GP21 (2016)

    Article  Google Scholar 

  • M.N. Yasin, D. Svirskis, A. Seyfoddin, I.D. Rupenthal, J. Control. Release 196, 208 (2014)

    Article  Google Scholar 

  • V.K. Yellepeddi, S. Palakurthi, J. Ocul. Pharmacol. Ther. 32, 67 (2016)

    Article  Google Scholar 

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Acknowledgements

This study was partially supported by the Basic Science and Platform Technology Program for Innovative Biological Medicine from the Japan Agency for Medical Research and Development (AMED, Japan), a Grant-in-Aid for Scientific Research (B) (17H02752) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT, Japan), the Business Incubation Program (BIP) from the Tohoku University (Japan), and a subsidy from the Terumo Foundation for Life Sciences and Arts (Japan).

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Authors and Affiliations

  1. Department of Finemechanics, Graduate School of Engineering, Tohoku University, 6-6-01 Aramaki, Aoba-ku, Sendai, 980-8579, Japan

    Yuto Sato & Hirokazu Kaji

  2. Division of Clinical Cell Therapy, United Centers for Advanced Research and Translational Medicine (ART), Tohoku University Graduate School of Medicine, 2-1 Seiryo, Aoba-ku, Sendai, 980-8575, Japan

    Nobuhiro Nagai & Toshiaki Abe

  3. Department of Biomedical Engineering, Graduate School of Biomedical Engineering, Tohoku University, 6-6-01 Aramaki, Aoba-ku, Sendai, 980-8579, Japan

    Hirokazu Kaji

Authors
  1. Yuto Sato
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  2. Nobuhiro Nagai
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  3. Toshiaki Abe
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  4. Hirokazu Kaji
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Correspondence to Hirokazu Kaji.

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Sato, Y., Nagai, N., Abe, T. et al. A multilayered sheet-type device capable of sustained drug release and deployment control. Biomed Microdevices 21, 60 (2019). https://doi.org/10.1007/s10544-019-0411-z

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  • DOI: https://doi.org/10.1007/s10544-019-0411-z

Keywords

  • Drug delivery system
  • Injectable
  • Sheet-type device
  • Ocular tissue
  • Retina