AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
Powered by AMiner. Clicking this button will take you away from SciOpen.
Home Nano Research Article
Article Link
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Research Article

Flurbiprofen microneedle patches for the management of acute postoperative pain

Huaqing Chu1,2, Yanyan Zhang2,3, Yuan Yang5, Jiangtao Xue2,4, Cong Li2, Wei Zhang3( ), Zhou Li2( ), Hui Zheng1( )
National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing 101400, China
Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha 410208, China
School of Life Science, Institute of Engineering Medicine, Beijing Institute of Technology, Beijing 100081, China
Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China
Show Author Information

Graphical Abstract

This study introduces an innovative genipin-crosslinked microneedle patches with controlled flurbiprofen release for effective and prolonged postoperative pain relief, showcasing improved mechanical strength and biocompatibility through crosslinking, as evidenced by in vivo analgesic performance and biosafety evaluations.

Abstract

Acute postoperative pain is commonly treated with flurbiprofen (FBP), but conventional delivery methods are suboptimal. This study prepared a new non-burst release microneedles (MNs) using genipin cross-linked gelatin (cGel). By adding varying amounts of genipin to modulate the crosslinking degree of cGel, the drug release behavior of the drug-loaded MNs in the skin can be altered. The crosslinking parameters that meet therapeutic requirements are selected, thus providing rapid and long-lasting analgesic effects. cGel solutions were successfully cross-linked, altering matrix material microstructure, confirmed by scanning electron microscope imaging and fourier transform infrared spectroscopy. MNs demonstrated increasing mechanical strength with higher crosslinking. Drug release rates were rapid initially, then slowed, exhibiting a characteristic of decreased release rates with increasing degrees of crosslinking. In vivo, FBP/cGel MNs significantly reduced allodynia and hyperalgesia post-surgery, with the greatest effect observed at 2–3 h post-surgery, and can maintain analgesia for up to 6 h. Biosafety tests confirmed good biocompatibility. FBP/cGel MNs effectively penetrate the stratum corneum, safely delivering drugs with significant analgesic effects, excellent mechanical properties, and good biocompatibility, representing a promising strategy for managing acute postoperative pain.

Keywords

microneedlepostoperative painflurbiprofennon-steroid anti-inflammatory drugcross-linked gelatin

Electronic Supplementary Material

Download File(s)
6751_ESM.pdf (1 MB)

References

[1]

Taylor, R. S.; Ullrich, K.; Regan, S.; Broussard, C.; Schwenkglenks, M.; Taylor, R. J.; Gordon, D. B.; Zaslansky, R.; Meissner, W.; Rothaug, J. et al. The impact of early postoperative pain on health-related quality of life. Pain Pract. 2013, 13, 515–523.
Crossref Google Scholar
[2]

Mitra, S.; Carlyle, D.; Kodumudi, G.; Kodumudi, V.; Vadivelu, N. New advances in acute postoperative pain management. Curr. Pain Headache Rep. 2018, 22, 35.
Crossref Google Scholar
[3]

Benyamin, R.; Trescot, A. M.; Datta, S.; Buenaventura, R.; Adlaka, R.; Sehgal, N.; Glaser, S. E.; Vallejo, R. Opioid complications and side effects. Pain Physician 2008, 11, S105–S120.
Google Scholar
[4]

Joshi, G. P.; Kehlet, H. Postoperative pain management in the era of ERAS: An overview. Best Pract. Res. Clin. Anaesthesiol. 2019, 33, 259–267.
Crossref Google Scholar
[5]

O’Neill, A.; Lirk, P. Multimodal analgesia. Anesthesiol. Clin. 2022, 40, 455–468.
Crossref Google Scholar
[6]

Schug, S. A.; Manopas, A. Update on the role of non-opioids for postoperative pain treatment. Best Pract. Res. Clin. Anaesthesiol. 2007, 21, 15–30.
Crossref Google Scholar
[7]

Gustafsson, U. O.; Scott, M. J.; Hubner, M.; Nygren, J.; Demartines, N.; Francis, N.; Rockall, T. A.; Young-Fadok, T. M.; Hill, A. G.; Soop, M. et al. Guidelines for perioperative care in elective colorectal surgery: Enhanced Recovery After Surgery (ERAS®) Society recommendations: 2018. World J. Surg. 2019, 43, 659–695.
Crossref Google Scholar
[8]

Cashman, J. N. The mechanisms of action of NSAIDs in analgesia. Drugs 1996, 52, 13–23.
Crossref Google Scholar
[9]

Gupta, A.; Bah, M. NSAIDs in the treatment of postoperative pain. Curr. Pain Headache Rep. 2016, 20, 62.
Crossref Google Scholar
[10]

Nathi, R.; Ketha, N. V. D. P.; Kowtarapu, L. P.; Muchakayala, S. K.; Konduru, N.; Saroja, B.; Marisetti, A. L. Flurbiprofen cataplasms: Development and validation of in-vitro dissolution methods and evaluation of multimedia dissolution profiles. Pharm. Sci. Adv. 2023, 1, 100018.
Crossref Google Scholar
[11]

Shah, K.; Gupta, J. K.; Chauhan, N. S.; Upmanyu, N.; Shrivastava, S. K.; Mishra, P. Prodrugs of NSAIDs: A review. Open Med. Chem. J. 2017, 11, 146–195.
Crossref Google Scholar
[12]

Nir, Y.; Paz, A.; Sabo, E.; Potasman, I. Fear of injections in young adults: Prevalence and associations. Am. J. Trop. Med. Hyg. 2003, 68, 341–344.
Crossref Google Scholar
[13]

Usach, I.; Martinez, R.; Festini, T.; Peris, J. E. Subcutaneous injection of drugs: Literature review of factors influencing pain sensation at the injection site. Adv. Ther. 2019, 36, 2986–2996.
Crossref Google Scholar
[14]

Prausnitz, M. R.; Langer, R. Transdermal drug delivery. Nat. Biotechnol. 2008, 26, 1261–1268.
Crossref Google Scholar
[15]

Jiang, J. Z.; Ma, T. Y.; Zhang, L. H.; Cheng, X. M.; Wang, C. H. The transdermal performance, pharmacokinetics, and anti-inflammatory pharmacodynamics evaluation of harmine-loaded ethosomes. Drug Dev. Ind. Pharm. 2020, 46, 101–108.
Crossref Google Scholar
[16]

Yu, Y. Q.; Yang, X.; Wu, X. F.; Fan, Y. B. Enhancing permeation of drug molecules across the skin via delivery in nanocarriers: Novel strategies for effective transdermal applications. Front. Bioeng. Biotechnol. 2021, 9, 646554.
Crossref Google Scholar
[17]

An, H.; Gu, Z.; Huang, Z.; Huo, T.; Xu, Y. X.; Dong, Y. Z.; Wen, Y. Q. Novel microneedle platforms for the treatment of wounds by drug delivery: A review. Colloids Surf. B Biointerfaces 2024, 233, 113636.
Crossref Google Scholar
[18]

Zheng, M. J.; Sheng, T.; Yu, J. C.; Gu, Z.; Xu, C. J. Microneedle biomedical devices. Nat. Rev. Bioeng. 2024, 2, 324–342.
Crossref Google Scholar
[19]

Nordquist, L.; Roxhed, N.; Griss, P.; Stemme, G. Novel microneedle patches for active insulin delivery are efficient in maintaining glycaemic control: An initial comparison with subcutaneous administration. Pharm. Res. 2007, 24, 1381–1388.
Crossref Google Scholar
[20]

Van Der Maaden, K.; Jiskoot, W.; Bouwstra, J. Microneedle technologies for (trans) dermal drug and vaccine delivery. J. Controlled Release 2012, 161, 645–655.
Crossref Google Scholar
[21]

Omatsu, T.; Chujo, K.; Miyamoto, K.; Okida, M.; Nakamura, K.; Aoki, N.; Morita, R. Metal microneedle fabrication using twisted light with spin. Opt. Express 2010, 18, 17967–17973.
Crossref Google Scholar
[22]

Chen, B. T.; Wei, J. S.; Tay, F. E. H.; Wong, Y. T.; Iliescu, C. Silicon microneedle array with biodegradable tips for transdermal drug delivery. Microsyst. Technol. 2008, 14, 1015–1019.
Crossref Google Scholar
[23]

Ita, K. Ceramic microneedles and hollow microneedles for transdermal drug delivery: Two decades of research. J. Drug Deliv. Sci. Technol. 2018, 44, 314–322.
Crossref Google Scholar
[24]
Han, J. P.; Sheng, T.; Zhang, Y. Q.; Cheng, H.; Gao, J. Q.; Yu, J. C.; Gu, Z. Bioresponsive immunotherapeutic materials. Adv. Mater., in press, https://doi.org/10.1002/adma.202209778.
[25]

Yang, Y.; Chu, H. Q.; Zhang, Y.; Xu, L. L.; Luo, R. Z.; Zheng, H.; Yin, T. L.; Li, Z. Rapidly separable bubble microneedle patch for effective local anesthesia. Nano Res. 2022, 15, 8336–8344.
Crossref Google Scholar
[26]

Luo, F. Q.; Chen, G. J.; Xu, W.; Zhou, D. J.; Li, J. X.; Huang, Y. C.; Lin, R.; Gu, Z.; Du, J. Z. Microneedle-array patch with pH-sensitive formulation for glucose-responsive insulin delivery. Nano Res. 2021, 14, 2689–2696.
Crossref Google Scholar
[27]

Hong, T.; Shen, X. Y.; Syeda, M. Z.; Zhang, Y.; Sheng, H. N.; Zhou, Y. P.; Xu, J. M.; Zhu, C. J.; Li, H. J.; Gu, Z. et al. Recent advances of bioresponsive polymeric nanomedicine for cancer therapy. Nano Res. 2023, 16, 2660–2671.
Crossref Google Scholar
[28]

Su, K.; Wang, C. M. Recent advances in the use of gelatin in biomedical research. Biotechnol. Lett. 2015, 37, 2139–2145.
Crossref Google Scholar
[29]

Echave, M. C.; Hernáez-Moya, R.; Iturriaga, L.; Pedraz, J. L.; Lakshminarayanan, R.; Dolatshahi-Pirouz, A.; Taebnia, N.; Orive, G. Recent advances in gelatin-based therapeutics. Expert Opin. Biol. Ther. 2019, 19, 773–779.
Crossref Google Scholar
[30]

Liang, H. C.; Chang, W. H.; Liang, H. F.; Lee, M. H.; Sung, H. W. Crosslinking structures of gelatin hydrogels crosslinked with genipin or a water-soluble carbodiimide. J. Appl. Polym. Sci. 2004, 91, 4017–4026.
Crossref Google Scholar
[31]

Bozzini, S.; Petrini, P.; Altomare, L.; Tanzi, M. C. Fabrication of chemically cross-linked porous gelatin matrices. J. Appl. Biomater. Biomech. 2009, 7, 194–199.
Crossref Google Scholar
[32]

Vijayakumar, V.; Subramanian, K. Diisocyanate mediated polyether modified gelatin drug carrier for controlled release. Saudi Pharm. J. 2014, 22, 43–51.
Crossref Google Scholar
[33]

Ahmed, R.; Ul Ain Hira, N.; Wang, M. W.; Iqbal, S.; Yi, J.; Hemar, Y. Genipin, a natural blue colorant precursor: Source, extraction, properties, and applications. Food Chem. 2024, 434, 137498.
Crossref Google Scholar
[34]

Kirchmajer, D. M.; Watson, C. A.; Ranson, M.; Panhuis, M. I. H. Gelapin, a degradable genipin cross-linked gelatin hydrogel. RSC Adv. 2013, 3, 1073–1081.
Crossref Google Scholar
[35]

Butler, M. F.; Ng, Y. F.; Pudney, P. D. A. Mechanism and kinetics of the crosslinking reaction between biopolymers containing primary amine groups and genipin. J. Polym. Sci. A Pol. Chem. 2003, 41, 3941–3953.
Crossref Google Scholar
[36]

Bigi, A.; Panzavolta, S.; Roveri, N. Hydroxyapatite-gelatin films: A structural and mechanical characterization. Biomaterials 1998, 19, 739–744.
Crossref Google Scholar
[37]

Ohri, R.; Wang, J. C. F.; Blaskovich, P. D.; Pham, L. N.; Costa, D. S.; Nichols, G. A.; Hildebrand, W. P.; Scarborough, N. L.; Herman, C. J.; Strichartz, G. R. Inhibition by local bupivacaine-releasing microspheres of acute postoperative pain from hairy skin incision. Anesth. Analg. 2013, 117, 717–730.
Crossref Google Scholar
[38]

Van De Loosdrecht, A. A.; Nennie, E.; Ossenkoppele, G. J.; Beelen, R. H. J.; Langenhuijsen, M. M. A. C. Cell mediated cytotoxicity against U 937 cells by human monocytes and macrophages in a modified colorimetric MTT assay: A methodological study. J. Immunol. Methods 1991, 141, 15–22.
Crossref Google Scholar
[39]

Zhen, Z.; Liu, X. L.; Huang, T.; Xi, T. F.; Zheng, Y. F. Hemolysis and cytotoxicity mechanisms of biodegradable magnesium and its alloys. Mater. Sci. Eng. C 2015, 46, 202–206.
Crossref Google Scholar
[40]

Chen, B. Z.; Zhang, L. Q.; Xia, Y. Y.; Zhang, X. P.; Guo, X. D. A basal-bolus insulin regimen integrated microneedle patch for intraday postprandial glucose control. Sci. Adv. 2020, 6, eaba7260.
Crossref Google Scholar
[41]

Friedman, M. Applications of the ninhydrin reaction for analysis of amino acids, peptides, and proteins to agricultural and biomedical sciences. J. Agric. Food Chem. 2004, 52, 385–406.
Crossref Google Scholar
[42]

Wang, Q. L.; Zhu, D. D.; Chen, Y.; Guo, X. D. A fabrication method of microneedle molds with controlled microstructures. Mater. Sci. Eng. C 2016, 65, 135–142.
Crossref Google Scholar
[43]

Duarte, A. M.; Pospisilova, E.; Reilly, E.; Mujenda, F.; Hamaya, Y.; Strichartz, G. R. Reduction of postincisional allodynia by subcutaneous bupivacaine: Findings with a new model in the hairy skin of the rat. Anesthesiology 2005, 103, 113–125.
Crossref Google Scholar
[44]

Podgórski, R.; Wojasiński, M.; Ciach, T. Nanofibrous materials affect the reaction of cytotoxicity assays. Sci. Rep. 2022, 12, 9047.
Crossref Google Scholar
Nano Research
Volume 17 Issue 8,
August 2024
Pages 7493-7503
DOI: 10.1007/s12274-024-6751-x
Cite this article:
Chu H, Zhang Y, Yang Y, et al. Flurbiprofen microneedle patches for the management of acute postoperative pain. Nano Research, 2024, 17(8): 7493-7503. https://doi.org/10.1007/s12274-024-6751-x
Topics:
Biological systems

424

Views

0

Crossref

0

Web of Science

0

Scopus

0

CSCD

Altmetrics
Received: 16 April 2024
Revised: 09 May 2024
Accepted: 11 May 2024
Published: 27 June 2024
© Tsinghua University Press 2024
Return