Journal of IKEEE (전기전자학회논문지)

Institute of Korean Electrical and Electronics Engineers (한국전기전자학회)
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Development and application of non-invasive drug delivery systems utilizing pulse power, and its application to mouse models

펄스파워를 적용한 비침습 약물 전달기 개발 및 마우스 모델로의 적용

  • Hwi-Chan Ham (Department of Mechanical and Aerospace Engineering, Seoul National University) ;
  • Kyu-Sik Kim (Department of Biomedical Sciences, Seoul National University College of Medicine) ;
  • Ji-Hwan Lee (Department of Mechanical Engineering, Seoul National University) ;
  • Hyung-Jin Choi (Department of Biomedical Sciences, Seoul National University College of Medicine) ;
  • Do-Nyun Kim (Department of Mechanical Engineering, Seoul National University) ;
  • Jai-Ick Yoh (Department of Mechanical and Aerospace Engineering, Seoul National University)
  • Received : 2024.03.14
  • Accepted : 2024.03.27
  • Published : 2024.03.31
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Abstract

Some drugs can offer far better medical effectiveness as it is injected through the intradermal layer of the skin, known as a needle-free injection. However, conventional needle-free devices might deliver a relatively large amount of drug in a just single spot of skin, splitting open the tissue layer structure, which might cause bruising and bleeding. By injecting the small volume with a fast repetition rate in a large surface area of skin, the patient may get much fewer injuries and pain. To achieve that specification, the driving force must be instantaneous and short-pulsed. Such a form of an injection device has been developed but the efficacy of those devices has been rarely examined. Therefore, this study developed the laser-induced microjet device that ejects microjet whose speed is ~310 m/s, during the 400~800 ㎲ of pulse time. The device can eject ~1 µL of the drug at the rate at which each shot repeated 10 shots per second. Using this specification, we evaluated the efficacy of drug injection onto mouse models. After injecting the insulin solution into the mouse model, the blood insulin level is detected, resulting in 20 % of blood insulin level with the ordinary needle syringe injection method.

일부 약물은 피부의 표피층 이하로 주입될 때 훨씬 더 효과적인 의료 효과를 제공할 수 있다. 그러나 전통적인 비침습 주입 장치는 피부의 한 부분에 상대적으로 많은 양의 약물을 전달하며, 이는 조직층 구조를 분리하여 멍과 출혈을 유발할 수 있다. 피부의 큰 표면적에 빠른 반복율로 소량을 주입함으로써 환자의 부상과 통증을 감소시킬 수 있다. 이를 위해서 약액을 분사하는 압력은 빠른 속도로 침투 가능 압력까지 상승되고 빠르게 하강하여 주입되지 않는 되튀김량을 줄이고, 주입량을 최소화해야한다. 이러한 형태의 비침습 주사 장치가 개발되었지만 그 장치들의 의학적 효능은 분석된 바가 거의 없다. 따라서 이 연구에서는 속도가 ~310m/s인 마이크로젯을 분사하는 레이저 유도 마이크로젯 장치를 개발했다. 펄스 시간은 400~800 ㎲이며 각 분사가 초당 10번 반복되는 속도로 약물을 약 1 µL 분사할 수 있습니다. 이러한 원리를 사용하여 우리는 마우스 모델에 대한 약물 주사의 효과를 평가했다. 마우스 모델에 인슐린 용액을 주입한 후 혈중 인슐린 농도를 측정하였으며, 일반 바늘 주사 주법과 동일한 값을 얻었다.

Keywords

Acknowledgement

This work was supported by Seoul National University Research Grant in 2020.

References

  1. Florentine, B. D., Frankel K., Raza A., Cobb J. C., Greaves T., Carriere C., and Martin S. E., "Local anesthesia for fine-needle aspiration biopsy of palpable breast masses: The effectiveness of a jet injection system," Diagn. Cytopathol, vol.17, no.6, pp.472-476, 1997. DOI: 10.1002/(sici)1097-0339 (199712)17:6<472::aid-dc18>3.0.co;2-j
  2. Houtzagers, C. M. "Multiple daily insulin injections: a multicentre study on acceptability and efficacy," Neth. J. Med, vol.33, no.1 pp.16-25, 1988.
  3. Pharm. D, Bremseth L. D., and Pass F, "Delivery of insulin by jet injection: recent observations," Diabete. Technol. & The. vol.3, no.2, pp.225-232, 2001. DOI: 10.1089/152091501300209598
  4. Rayman, G., Walker R., and Day J. L, "Patient experience with a jet injector," Diabetic Med, vol.6, no.3, pp.274-276, 1989. DOI: 10.1111/j.1464-5491.1989.tb01160.x
  5. Arora, A., Hakim I., Baxter J., Rathnasingham R., Srinivasan R., Fletcher A. D., and Mitragotri S, "Needle-free delivery of macromolecules across the skin by nanoliter-volume pulsed microjets," PNAS, vol.104, no.11, pp.4255-4260, 2007. DOI: 10.1073/pnas.07001821
  6. Schramm-Baxter, J., and Mitragotri S, "Needle-free jet injections: dependence of jet penetration and dispersion in the skin on jet power," J. Control. Release vol.97, no.3, pp.527-535,2004. DOI: 10.1016/j.jconrel.2004.04.006
  7. Peters, I. R., Tagawa Y., Oudalov N., Sun C., Prosperetti A., Lohse D., and Meer D, "Highly focused supersonic microjets: numerical simulations," J. fluid Mech 719, pp.587-605, 2013. DOI: 10.1017/jfm.2013.26
  8. Ham, H., Jang H., and Yoh J. J, "A check valve controlled laser-induced microjet for uniform transdermal drug delivery," AIP Adv, vol.7, no.12, pp.125206, 2017. DOI: 10.1063/1.4999962
  9. Hale, G. M., and Querry R. M, "Optical constants of water in the 200-nm to 200- m wavelength region," Spie Milestone Series Ms 118: 80-88, 1996.
  10. Hamed K., Liu Q., and Ravi-Chandar K, "Dynamic tensile characterization of pig skin," Acta Mech. Sin, vol.30, no.2, pp.125-132, 2014. DOI: 10.1007/s10409-014-0042-9
  11. J. A. Gallagher, A. N. Annaidh, and K. Bruy'ere, "Dynamic tensile properties of human skin," Paper presented at IRCOBI Conference 2012, 12-14 September 2012, Dublin Ireland, 2012. http://hdl.handle.net/10197/4772
  12. Jang, Hun-jae, Hur E., Kim Y., Lee S., Kang N., and Yoh J, "Laser-induced microjet injection into preablated skin for more effective transdermal drug delivery," J. Biomed. Opt, vol.19, no.11, pp.118002, 2014. DOI: 10.1117/1.JBO.19.11.118002
  13. Rini, Christopher James, Elaine McVey, Diane Sutter, Stephen Keith, Heinz-Joerg Kurth, Leszek Nosek, Christoph Kapitza, Kerstin Rebrin, Laurence Hirsch, and Ronald J. Pettis, "Intradermal insulin infusion achieves faster insulin action than subcutaneous infusion for 3-day wear," Drug delivery and translational research, vol.5, no.4, pp.332-345, 2015. DOI: 10.1007/s13346-015-0239-x