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Nitinol actuated soft structures towards transnasal drug delivery: a pilot cadaver study

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Abstract

Sudden hearing loss can be treated noninvasively by administering drugs to the middle ear (≈1 ml) via the eustachian tube. The nasopharyngeal cavity requires high dexterity manipulation as it is restricted by the nasal vestibule, and precise drug delivery through the small cavity can allow previously unreachable areas to be reconsidered for localized delivery. Nitinol has shape memory capabilities and can be used for distal actuation accessed from small lumen and a tortuous path. The drug delivery device (DDD) is a soft and needle-sized (2 mm) and comprises of Nitinol, ribbon spring, and a drug delivery tube. By controlling the input voltage to the Nitinol, bending of the device at different angles could be achieved, and the ribbon spring works antagonistically to the Nitinol to revert to the initial position once deactivated. The actuation of the device and its corresponding bending are calculated in vitro and found to have a bending angle ranging between 36.2 and 66.8° for applied voltages of 1.2–2.0 V, with surface temperature of 45.6–154 °C. The DDD is able to actuate 200 cycles with ≈91–76% retention of bending performance, with a temperature increase of ≈8.5–9% when 1.2–2.0 V is applied. Addition of soft insulating material shows ≈34–62% reduction in the surface temperature in the first cycle and ≈37–59% over 200 cycles when actuated at 1.2–2.0 V. The active steering and navigation capabilities of the DDD are demonstrated in simulated environments (based on the eustachian tube dimensions of adult and infant). Preclinical testing in human cadavers is demonstrated and suggests the developed DDD controlled by varying the input voltages for bending, and mechanically varied drug delivery may be a feasible option for localized drug delivery in eustachian tube.

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Acknowledgments

Authors would like to thank the Department of Otolaryngology at the National University Hospital, Khoo Teck Puat Advanced Surgery Training Centre for assistance with the cadaver experiments. This work was supported in part by the NMRC Bedside & Bench under grant R-397-000-245-511, Singapore Academic Research Fund under Grant R-397-000-297-114, Singapore MOE Tier-1 Academic Research Fund entitled "HENA: HYDROGEL-MATRIX EXPEDITED NITINOL ACTUATION" awarded to Dr. Hongliang Ren.

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Authors and Affiliations

  1. Department of Biomedical Engineering, National University of Singapore, Singapore, 117583, Singapore

    Manivannan Sivaperuman Kalairaj, Bok Seng Yeow & Hongliang Ren

  2. Department of Otorhinolaryngology – Head and Neck Surgery, Singapore General Hospital, Singapore, 169856, Singapore

    Chwee Ming Lim

  3. Duke–NUS Graduate Medical School, Singapore, 169857, Singapore

    Chwee Ming Lim

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  1. Manivannan Sivaperuman Kalairaj
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Correspondence to Hongliang Ren.

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Conflict of interest

This study is funded as declared in the acknowledgments. Authors (Mr. Manivannan Sivaperuman Kalairaj, Mr. Bok Seng Yeow, Drs. Chwee Ming Lim, and Hongliang Ren) declare that they have no further conflict of interest as declared in the Conflict of Interest (ICMJE) document.

Research involving human participants and/or animals

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of retrospective study, formal consent is not required. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study. Any participation in the study is voluntary, and identities of participants are kept anonymous.

The cadaver used in this study is purchased from MedCure under the study Adaptive and Compliant Transoral Robotic Surgery (ACTORS) with Flexible Manipulators and Intelligent Guidance & NHG DSRB Ref: 2017/00008.

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Sivaperuman Kalairaj, M., Yeow, B.S., Lim, C.M. et al. Nitinol actuated soft structures towards transnasal drug delivery: a pilot cadaver study. Med Biol Eng Comput 58, 611–623 (2020). https://doi.org/10.1007/s11517-019-02102-x

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