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Toward a solid microneedle patch for rapid and enhanced local analgesic action

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Abstract

Analgesic creams find widespread application as adjuncts for localized anesthesia prior to surgical procedures. Nevertheless, the onset of analgesic action is protracted due to the skin barrier’s inherent characteristics, which necessitates prolonged intervals of patient and clinician waiting, consequently impinging upon patient compliance and clinician workflow efficiency. In this work, a biodegradable microneedles (MNs) patch was introduced to enhance the intradermal administration of lidocaine cream to achieve rapid analgesia through a minimally invasive and conveniently accessible modality. The polylactic acid (PLA) MNs were mass-produced using a simple hot-pressing method and served the purpose of creating microchannels across the skin’s surface for rapid absorption of lidocaine cream. Optical and electron microscopes were applied to meticulously scrutinize the morphology of the fabricated MNs, and the comprehensive penetration tests involving dynamometer tests, evaluation on porcine cadaver skin, artificial film, optical coherence tomography (OCT), transepidermal water loss, and analysis on rats’ skins, demonstrated the robust mechanical strength of PLA MNs for successful intradermal penetration. The behavioral pain sensitivity tests on living rats using Von Frey hair filaments revealed that the MN-assisted lidocaine treatment expeditiously accelerated the onset of action from 40 to 10 min and substantially enhanced the efficacy of localized anesthesia. Furthermore, different treatment protocols encompassing the sequence of drug application relative to MN treatment, MN dimensions, and the frequency of MN insertions exhibited noteworthy influence on the resultant local anesthesia efficacy. Together, these results demonstrated that the lidocaine cream followed by diverse PLA MN treatments would be a promising strategy for rapid clinical local anesthesia with wide-ranging applications.

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References

  1. Tobe M, Suto T, Saito S. The history and progress of local anesthesia: multiple approaches to elongate the action. J Anesth. 2018;32(4):632–6.

    Article  PubMed  Google Scholar 

  2. Thorsell M, Holst P, Hyldahl HC, Weidenhielm L. Pain control after total knee arthroplasty: a prospective study comparing local infiltration anesthesia and epidural anesthesia. Orthopedics. 2010;33(2):75–80.

    Article  PubMed  Google Scholar 

  3. Obokhare J. Local and regional blocks for complex facial wound repair. Facial Plast Surg. 2021;37(04):446–53.

    Article  CAS  PubMed  Google Scholar 

  4. Ramadon D, Sutrisna LFP, Harahap Y, Putri KSS, Ulayya F, Hartrianti P, et al. Enhancing intradermal delivery of lidocaine by dissolving microneedles: comparison between hyaluronic acid and poly(vinyl pyrrolidone) backbone polymers. Pharmaceutics. 2023;15(1):289.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Xin Y, Wen X, Hamblin MR, Jiang X. Transdermal delivery of topical lidocaine in a mouse model is enhanced by treatment with cold atmospheric plasma. J Cosmet Dermatol. 2021;20(2):626–35.

    Article  PubMed  Google Scholar 

  6. Strichartz GR. The inhibition of sodium currents in myelinated nerve by quaternary derivatives of lidocaine. J Gen Physiol. 1973;62(1):37–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Fabbrocini G, De Vita V, Izzo R, Monfrecola G. The use of skin needling for the delivery of a eutectic mixture of local anesthetics. G Ital Dermatol Venereol. 2014;149(5):581–5.

    CAS  PubMed  Google Scholar 

  8. Lander J, Hodgins M, Nazarali S, McTavish J, Ouellette J, Friesen E. Determinants of success and failure of EMLA. Pain. 1996;64(1):89–97.

    Article  CAS  PubMed  Google Scholar 

  9. Bahmani S, Khajavi R, Ehsani M, Rahimi MK, Kalaee MR. Transdermal drug delivery system of lidocaine hydrochloride based on dissolving gelatin/sodium carboxymethylcellulose microneedles. AAPS Open. 2023;9(1):7.

    Article  Google Scholar 

  10. Zempsky WT, Robbins B, McKay K. Reduction of topical anesthetic onset time using ultrasound: a randomized controlled trial prior to venipuncture in young children. Pain Med. 2008;9(7):795–802.

    Article  PubMed  Google Scholar 

  11. Manjunatha RG, Prasad R, Sharma S, Narayan RP, Koul V. Iontophoretic delivery of lidocaine hydrochloride through ex-vivo human skin. J Dermatol Treat. 2020;31(2):191–9.

    Article  CAS  Google Scholar 

  12. Zhang D, Ye D, Jing P, Tan X, Qiu L, Li T, et al. Design, optimization and evaluation of co-surfactant free microemulsion-based hydrogel with low surfactant for enhanced transdermal delivery of lidocaine. Int J Pharmaceut. 2020;586:119415.

    Article  CAS  Google Scholar 

  13. Franz-Montan M, Baroni D, Brunetto G, Vieira Sobral VR, Goncalves da Silva CM, Venancio P, et al. Liposomal lidocaine gel for topical use at the oral mucosa: characterization, in vitro assays and in vivo anesthetic efficacy in humans. J Liposome Res. 2015;25(1):11–9.

  14. Leng F, Wan J, Liu W, Tao B, Chen X. Prolongation of epidural analgesia using solid lipid nanoparticles as drug carrier for lidocaine. Reg Anesth Pain Med. 2012;37(2):159–65.

    Article  CAS  PubMed  Google Scholar 

  15. Bakonyi M, Berko S, Kovacs A, Budai-Szucs M, Kis N, Eros G, et al. Application of quality by design principles in the development and evaluation of semisolid drug carrier systems for the transdermal delivery of lidocaine. J Drug Delivery Sci Technol. 2018;44:136–45.

    Article  CAS  Google Scholar 

  16. Babaie S, Ghanbarzadeh S, Davaran S, Kouhsoltani M, Hamishehkar H. Nanoethosomes for dermal delivery of lidocaine. Adv Pharm Bull. 2015;5(4):549–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zhao X, Sun Y, Li Z. Topical anesthesia therapy using lidocaine-loaded nanostructured lipid carriers: tocopheryl polyethylene glycol 1000 succinate-modified transdermal delivery system. Drug Des, Dev Ther. 2018;12:4231–40.

    Article  CAS  Google Scholar 

  18. Ramadon D, McCrudden MTC, Courtenay AJ, Donnelly RF. Enhancement strategies for transdermal drug delivery systems: current trends and applications. Drug Deliv Transl Re. 2021;12(4):758–91.

    Article  Google Scholar 

  19. Chen BZ, He MC, Zhang XP, Fei WM, Cui Y, Guo XD. A novel method for fabrication of coated microneedles with homogeneous and controllable drug dosage for transdermal drug delivery. Drug Deliv Transl Re. 2022;12(11):2730–9.

    Article  CAS  Google Scholar 

  20. Rouphael NG, Paine M, Mosley R, Henry S, McAllister DV, Kalluri H, et al. The safety, immunogenicity, and acceptability of inactivated influenza vaccine delivered by microneedle patch (TIV-MNP 2015): a randomised, partly blinded, placebo-controlled, phase 1 trial. Lancet. 2017;390(10095):649–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Al-Japairai KAS, Mahmood S, Almurisi SH, Venugopal JR, Hilles AR, Azmana M, et al. Current trends in polymer microneedle for transdermal drug delivery. Int J Pharm. 2020;587:119673.

    Article  Google Scholar 

  22. Li JY, Feng YH, He YT, Hu LF, Liang L, Zhao ZQ, et al. Thermosensitive hydrogel microneedles for controlled transdermal drug delivery. Acta Biomater. 2022;153:308–19.

    Article  CAS  PubMed  Google Scholar 

  23. Al-Kasasbeh R, Brady AJ, Courtenay AJ, Larraneta E, McCrudden MTC, O’Kane D, et al. Evaluation of the clinical impact of repeat application of hydrogel-forming microneedle array patches. Drug Deliv Transl Res. 2020;10(3):690–705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Howells O, Blayney GJ, Gualeni B, Birchall JC, Eng PF, Ashraf H, et al. Design, fabrication, and characterisation of a silicon microneedle array for transdermal therapeutic delivery using a single step wet etch process. Eur J Pharm Biopharm. 2022;171:19–28.

    Article  CAS  PubMed  Google Scholar 

  25. Hong C, Zhang G, Zhang W, Liu J, Zhang J, Chen Y, et al. Hair grows hair: Dual-effective hair regrowth through a hair enhanced dissolvable microneedle patch cooperated with the pure yellow light irradiation. Appl Mater Today. 2021;25:101188.

    Article  Google Scholar 

  26. Sheng T, Luo B, Zhang W, Ge X, Yu J, Zhang Y, et al. Microneedle-mediated vaccination: innovation and translation. Adv Drug Delivery Rev. 2021;179:113919.

    Article  CAS  Google Scholar 

  27. Bui VD, Son S, Xavier W, Nguyen VQ, Jung JM, Lee J, et al. Dissolving microneedles for long-term storage and transdermal delivery of extracellular vesicles. Biomaterials. 2022;287:121644.

    Article  CAS  PubMed  Google Scholar 

  28. Chen BZ, Zhao ZQ, Shahbazi M-A, Guo XD. Microneedle-based technology for cell therapy: current status and future directions. Nanoscale Horiz. 2022;7(7):715–28.

    Article  CAS  PubMed  Google Scholar 

  29. Chen X, Wang L, Yu H, Li C, Feng J, Haq F, et al. Preparation, properties and challenges of the microneedles-based insulin delivery system. J Controlled Release. 2018;288:173–88.

    Article  CAS  Google Scholar 

  30. Li WX, Zhang XP, Chen BZ, Fei WM, Cui Y, Zhang CY, et al. An update on microneedle-based systems for diabetes. Drug Deliv Transl Re. 2022;12(10):2275–86.

    Article  Google Scholar 

  31. Huang Y, Yu H, Wang L, Shen D, Ni Z, Ren S, et al. Research progress on cosmetic microneedle systems: preparation, property and application. Eur Polym J. 2022;163: 110942.

    Article  CAS  Google Scholar 

  32. Larraneta E, Lutton REM, Woolfson AD, Donnelly RF. Microneedle arrays as transdermal and intradermal drug delivery systems: materials science, manufacture and commercial development. Mater Sci Eng R Rep. 2016;104:1–32.

    Article  Google Scholar 

  33. Dabholkar N, Gorantla S, Waghule T, Rapalli VK, Kothuru A, Goel S, et al. Biodegradable microneedles fabricated with carbohydrates and proteins: revolutionary approach for transdermal drug delivery. Int J Biol Macromol. 2021;170:602–21.

    Article  CAS  PubMed  Google Scholar 

  34. Serrano G, Almudever P, Serrano JM, Cortijo J, Faus C, Reyes M, et al. Microneedling dilates the follicular infundibulum and increases transfollicular absorption of liposomal sepia melanin. Clin, Cosmet Invest Dermatol. 2015;8:313–8.

    Article  Google Scholar 

  35. Shin Y, Kim J, Seok JH, Park H, Cha H-R, Ko SH, et al. Development of the H3N2 influenza microneedle vaccine for cross-protection against antigenic variants. Sci Rep. 2022;12(1):12189.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Lee H, Min HS, Jang M, Kang G, Gong S, Lee C, et al. Lidocaine-loaded dissolving microneedle for safe local anesthesia on oral mucosa for dental procedure. Expert Opin Drug Deliv. 2023;20(9):1251–65.

    Google Scholar 

  37. Lee B-M, Lee C, Lahiji SF, Jung U-W, Chung G, Jung H. Dissolving microneedles for rapid and painless local anesthesia. Pharmaceutics. 2020;12(4):366–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Courtenay AJ, McAlister E, McCrudden MTC, Vora L, Steiner L, Levin G, et al. Hydrogel-forming microneedle arrays as a therapeutic option for transdermal esketamine delivery. J Control Release. 2020;322:177–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Vora LK, Moffatt K, Tekko IA, Paredes AJ, Volpe-Zanutto F, Mishra D, et al. Microneedle array systems for long-acting drug delivery. Eur J Pharm Biopharm. 2021;159:44–76.

    Article  CAS  PubMed  Google Scholar 

  40. Zhao ZQ, Zhang BL, Chu HQ, Liang L, Chen BZ, Zheng H, et al. A high-dosage microneedle for programmable lidocaine delivery and enhanced local long-lasting analgesia. Biomater Adv. 2022;133:112620.

    Article  PubMed  Google Scholar 

  41. Hao YY, Yang Y, Li QY, Zhang XP, Shen CB, Zhang C, et al. Effect of polymer microneedle pre-treatment on drug distributions in the skin in vivo. J Drug Target. 2020;28(7–8):811–7.

    Article  CAS  PubMed  Google Scholar 

  42. Chen BZ, Liu JL, Li QY, Wang ZN, Zhang XP, Shen CB, et al. Safety evaluation of solid polymer microneedles in human volunteers at different application sites. ACS Appl Bio Mater. 2019;2(12):5616–25.

    Article  CAS  PubMed  Google Scholar 

  43. Yang Y, Chen BZ, Zhang XP, Zheng H, Li Z, Zhang CY, et al. Conductive microneedle patch with electricity-triggered drug release performance for atopic dermatitis treatment. ACS Appl Mater Interfaces. 2022;14(28):31645–54.

    Article  CAS  PubMed  Google Scholar 

  44. Zhang XP, Zhang BL, Chen BZ, Zhao ZQ, Fei WM, Cui Y, et al. Dissolving microneedle rollers for rapid transdermal drug delivery. Drug Deliv and Transl Re. 2022;12(2):459–71.

    Article  Google Scholar 

  45. Lhernould MS, Deleers M, Delchambre A. Hollow polymer microneedles array resistance and insertion tests. Int J Pharm. 2015;480(1–2):152–7.

    Article  CAS  PubMed  Google Scholar 

  46. Donnelly RF, Majithiya R, Singh TRR, Morrow DIJ, Garland MJ, Demir YK, et al. Design, optimization and characterisation of polymeric microneedle arrays prepared by a novel laser-based micromoulding technique. Pharm Res. 2011;28(1):41–57.

    Article  CAS  PubMed  Google Scholar 

  47. Liu S, Jin MN, Quan YS, Kamiyama F, Katsumi H, Sakane T, et al. The development and characteristics of novel microneedle arrays fabricated from hyaluronic acid, and their application in the transdermal delivery of insulin. J Controlled Release. 2012;161(3):933–41.

  48. Gomaa YA, Morrow DIJ, Garland MJ, Donnelly RF, El-Khordagui LK, Meidan VM. Effects of microneedle length, density, insertion time and multiple applications on human skin barrier function: assessments by transepidermal water loss. Toxicol In Vitro. 2010;24(7):1971–8.

    Article  CAS  PubMed  Google Scholar 

  49. Li M, Vora LK, Peng K, Donnelly RF. Trilayer microneedle array assisted transdermal and intradermal delivery of dexamethasone. Int J Pharm. 2022;612:121295.

    Article  CAS  PubMed  Google Scholar 

  50. Tena B, Escobar B, Jose Arguis M, Cantero C, Rios J, Gomar C. Reproducibility of electronic von Frey and von Frey monofilaments testing. Clin J Pain. 2012;28(4):318–23.

    Article  PubMed  Google Scholar 

  51. Yang H, Kang G, Jang M, Um DJ, Shin J, Kim H, et al. Development of lidocaine-loaded dissolving microneedle for rapid and efficient local anesthesia. Pharmaceutics. 2020;12(11):1067.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Li QY, Zhang JN, Chen BZ, Wang QL, Guo XD. A solid polymer microneedle patch pretreatment enhances the permeation of drug molecules into the skin. RSC Adv. 2017;7(25):15408–15.

    Article  CAS  Google Scholar 

  53. Lutton REM, Moore J, Larrañeta E, Ligett S, Woolfson AD, Donnelly RF. Microneedle characterisation: the need for universal acceptance criteria and GMP specifications when moving towards commercialisation. Drug Deliv and Transl Re. 2015;5(4):313–31.

    Article  Google Scholar 

  54. Kim M, Jung B, Park J-H. Hydrogel swelling as a trigger to release biodegradable polymer microneedles in skin. Biomaterials. 2012;33(2):668–78.

    Article  CAS  PubMed  Google Scholar 

  55. Wang H, Xu J, Xiang L. Microneedle-mediated transcutaneous immunization: potential in nucleic acid vaccination. Adv Healthc Mater. 2023;2300339.

  56. Yan G, Warner KS, Zhang J, Sharma S, Gale BK. Evaluation needle length and density of microneedle arrays in the pretreatment of skin for transdermal drug delivery. Int J Pharm. 2010;391(1–2):7–12.

    Article  CAS  PubMed  Google Scholar 

  57. Bal SM, Caussin J, Pavel S, Bouwstra JA. In vivo assessment of safety of microneedle arrays in human skin. Eur J Pharm Sci. 2008;35(3):193–202.

    Article  CAS  PubMed  Google Scholar 

  58. Garland MJ, Migalska K, Mazlelaa T, Mahmood T, Raghu T, Singh R, et al. Microneedle arrays as medical devices for enhanced transdermal drug delivery. Expert Rev Med Devices. 2011;8(4):459–82.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing, 100029, China

    Yue Liu, Ze Qiang Zhao, Ling Liang, Li Yue Jing, Bo Zhi Chen & Xin Dong Guo

  2. Beijing Laboratory of Biomedical Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, China

    Yue Liu, Ze Qiang Zhao, Ling Liang & Li Yue Jing

  3. School of Pharmacy, Changzhou University, Changzhou, 213164, Jiangsu, China

    Jianhao Wang

  4. Department of Endoscopy Center, The First Affiliated Hospital of Xiamen University, Xiamen, 361000, China

    Yun Dai

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  1. Yue Liu
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Correspondence to Jianhao Wang, Yun Dai, Bo Zhi Chen or Xin Dong Guo.

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Animal studies were approved by the institutional animal care committee of National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital (The ethical approval number: NCC2021A226). All procedures of animal studies were conducted in accordance with the animal guidelines for care and use of laboratory.

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Liu, Y., Zhao, Z.Q., Liang, L. et al. Toward a solid microneedle patch for rapid and enhanced local analgesic action. Drug Deliv. and Transl. Res. (2024). https://doi.org/10.1007/s13346-023-01486-6

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