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微针贴片负载利多卡因在皮肤创面的镇痛研究
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Abstract:
目的:研发一种无痛、快速、经皮给药的局麻镇痛载药方式。方法:首先利用微成型技术制备出含有利多卡因的微针贴片(MNs-Lido),对其进行物理、化学表征,利用大鼠足底切口疼痛模型检测MNs-Lido的镇痛效果,将大鼠随机分为3组:空白组(Blank组)、不载药物的MNs组(MNs组)和MNs-Lido组。大鼠术前先用Von-Frey测量机械缩足阈值(PWT),使用异氟醚麻醉后,建立足底切口疼痛模型,术后1天记录各组大鼠的PWT。结果:Blank组和MNs组相比差异无统计学意义;与Blank组和MNs相比,MNs-Lido组的阈值在给药后15、30、45分钟时有显著改善,在60分钟时仍存在镇痛效果,因此证明利多卡因的麻醉效果可以维持60分钟。结论:MNs-Lido在皮肤创面镇痛中表现出有效的镇痛效果,其持续麻醉效果至少持续60分钟。本研究为皮肤创面镇痛提供了一种快速、无痛的局部麻醉方法。
Objective: To develop a painless, rapid, and transdermal local anesthesia and analgesia method. Methods: Firstly, microneedle patches loaded with lidocaine (MNs-Lido) were fabricated using microfabrication technology and characterized physically and chemically. The analgesic effect of MNs-Lido was evaluated using a rat plantar incision pain model. Rats were randomly divided into three groups: Blank group, MNs group without drug, and MNs-Lido group. The mechanical withdrawal threshold (PWT) was measured using the Von-Frey test before surgery. After isoflurane anesthesia, a plantar incision pain model was established, and PWT of each group was recorded 1 day after surgery. Results: There was no significant difference between the Blank group and MNs group. Compared with the Blank group and MNs group, PWT in the MNs-Lido group was significantly improved at 15, 30, and 45 minutes after administration, and the analgesic effect was still observed at 60 minutes, indicating that the anesthetic effect of lidocaine could last for at least 60 minutes. Conclusion: MNs-Lido exhibited effective analgesic effect on skin wounds, with a sustained anesthetic effect of at least 60 minutes. This study provides a rapid and painless local anesthesia method for analgesia of skin wounds.
[1] | Ragsdale, D.S., McPhee, J.C., Scheuer, T. and Catterall, W.A. (1994) Molecular Determinants of State-Dependent Block of Na+ Channels by Local Anesthetics. Science, 265, 1724-1728. https://doi.org/10.1126/science.8085162 |
[2] | Ragsdale, D.S., McPhee, J.C., Scheuer, T. and Catterall, W.A. (1996) Common Molecular Determinants of Local Anesthetic, Antiarrhythmic, and Anticonvulsant Block of Voltage-Gated Na+ Channels. Proceedings of the National Academy of Sciences of the United States of America, 93, 9270-9275. https://doi.org/10.1073/pnas.93.17.9270 |
[3] | Ragsdale, D.S., Scheuer, T. and Catterall, W.A. (1991) Frequency and Voltage-Dependent Inhibition of type IIA Na+ Channels, Expressed in a Mammalian Cell Line, by Local Anesthetic, Antiarrhythmic, and Anticonvulsant Drugs. Molecular Pharmacology, 40, 756-765. |
[4] | Lee, B., Lee, C., Lahiji, S.F., Jung, U., Chung, G. and Jung, H. (2020) Dissolving Microneedles for Rapid and Painless Local Anesthesia. Pharmaceutics, 12, Article 366. https://doi.org/10.3390/pharmaceutics12040366 |
[5] | Zhu, T., Yu, X., Yi, X., Guo, X., Li, L., Hao, Y., et al. (2022) Lidocaine-Loaded Hyaluronic Acid Adhesive Microneedle Patch for Oral Mucosal Topical Anesthesia. Pharmaceutics, 14, Article 686. https://doi.org/10.3390/pharmaceutics14040686 |
[6] | Yang, Y., Chu, H., Zhang, Y., Xu, L., Luo, R., Zheng, H., et al. (2022) Rapidly Separable Bubble Microneedle Patch for Effective Local Anesthesia. Nano Research, 15, 8336-8344. https://doi.org/10.1007/s12274-022-4508-y |
[7] | Daly, S., Claydon, N.C.A., Newcombe, R.G., Seong, J., Addy, M. and West, N.X. (2021) Randomised Controlled Trial of a Microneedle Patch with a Topical Anaesthetic for Relieving the Pain of Dental Injections. Journal of Dentistry, 107, Article ID: 103617. https://doi.org/10.1016/j.jdent.2021.103617 |
[8] | Xie, X., Pascual, C., Lieu, C., Oh, S., Wang, J., Zou, B., et al. (2016) Analgesic Microneedle Patch for Neuropathic Pain Therapy. ACS Nano, 11, 395-406. https://doi.org/10.1021/acsnano.6b06104 |
[9] | Liu, Y., Zhao, Z.Q., Liang, L., et al. (2024) Toward a Solid Microneedle Patch for Rapid and Enhanced Local Analgesic Action. https://doi.org/10.21203/rs.3.rs-3316431/v1 |
[10] | Batra, P., Dawar, A. and Miglani, S. (2020) Microneedles and Nanopatches-Based Delivery Devices in Dentistry. Discoveries, 8, e116. https://doi.org/10.15190/d.2020.13 |
[11] | Gangadharan, V., Zheng, H., Taberner, F.J., Landry, J., Nees, T.A., Pistolic, J., et al. (2022) Neuropathic Pain Caused by Miswiring and Abnormal End Organ Targeting. Nature, 606, 137-145. https://doi.org/10.1038/s41586-022-04777-z |
[12] | Smith, T.J., Wang, E.J. and Loprinzi, C.L. (2023) Cutaneous Electroanalgesia for Relief of Chronic and Neuropathic Pain. New England Journal of Medicine, 389, 158-164. https://doi.org/10.1056/nejmra2110098 |
[13] | Finsterer, J. and Scorza, F.A. (2022) Small Fiber Neuropathy. Acta Neurologica Scandinavica, 145, 493-503. https://doi.org/10.1111/ane.13591 |
[14] | Debroas, G., Hoeffel, G., Reynders, A. and Ugolini, S. (2018) Interactions neuro-immunes dans la peau. Un lien entre douleur et immunité. Neuroimmune Interactions in the Skin: A Link between Pain and Immunity. Medicine Sciences, 34, 432-438. https://doi.org/10.1051/medsci/20183405016 |
[15] | Walk, D. (2018) Measures of Cutaneous Pain Perception and Nociceptor Density: More than Skin Deep. Muscle & Nerve, 58, 472-474. https://doi.org/10.1002/mus.26199 |
[16] | Misery, L., Loser, K. and St?nder, S. (2016) Sensitive Skin. Journal of the European Academy of Dermatology and Venereology, 30, 2-8. https://doi.org/10.1111/jdv.13532 |
[17] | Upton, D. and Andrews, A. (2013) Pain and Trauma in Negative Pressure Wound Therapy: A Review. International Wound Journal, 12, 100-105. https://doi.org/10.1111/iwj.12059 |
[18] | Bae, S., Ji, J., Oh, J., Won, J., Ryu, Y., Lee, H., et al. (2021) The Role of Skin Mast Cells in Acupuncture Induced Analgesia in Animals: A Preclinical Systematic Review and Meta-Analysis. The Journal of Pain, 22, 1560-1577. https://doi.org/10.1016/j.jpain.2021.06.006 |
[19] | Lee, E.K., Kim, M.K. and Lee, C.H. (2019) Skin-mountable Biosensors and Therapeutics: A Review. Annual Review of Biomedical Engineering, 21, 299-323. https://doi.org/10.1146/annurev-bioeng-060418-052315 |
[20] | Wójcik-Pastuszka, D., Stawicka, K., Dry?, A. and Musia?, W. (2023) Influence of HA on Release Process of Anionic and Cationic API Incorporated into Hydrophilic Gel. International Journal of Molecular Sciences, 24, Article 5606. https://doi.org/10.3390/ijms24065606 |
[21] | Kochhar, J.S., Lim, W.X.S., Zou, S., Foo, W.Y., Pan, J. and Kang, L. (2013) Microneedle Integrated Transdermal Patch for Fast Onset and Sustained Delivery of Lidocaine. Molecular Pharmaceutics, 10, 4272-4280. https://doi.org/10.1021/mp400359w |