Skip to main content

Advertisement

Log in

AgNPs-Modified Polylactic Acid Microneedles: Preparation and In Vivo/In Vitro Antimicrobial Studies

  • Original Research Article
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Objective

To prepare polylactic acid microneedles (PLAMNs) with sustained antibacterial effect to avoid skin infection caused by traditional MNs-based biosensors.

Methods

Silver nanoparticles (AgNPs) were synthesized using an in-situ reduction process with polydopamine (PDA). PLAMNs were fabricated using the hot-melt method. A series of pressure tests and puncture experiments were conducted to confirm the physicochemical properties of PLAMNs. Then AgNPs were modified on the surface of PLAMNs through in-situ reduction of PDA, resulting in the formation of PLAMNs@PDA-AgNPs. The in vitro antibacterial efficacy of PLAMNs@PDA-AgNPs was evaluated using agar diffusion assays and bacterial liquid co-culture approach. Wound healing and simulated long-term application were performed to assess the in vivo antibacterial effectiveness of PLAMNs@PDA-AgNPs.

Results

The MNs array comprised 169 tiny needle tips in pyramidal rows. Strength and puncture tests confirmed a 100% puncture success rate for PLAMNs on isolated rat skin and tin foil. SEM analysis revealed the integrity of PLAMNs@PDA-AgNPs with the formation of new surface substances. EDS analysis indicated the presence of silver elements on the surface of PLAMNs@PDA-AgNPs, with a content of 14.44%. Transepidermal water loss (TEWL) testing demonstrated the rapid healing of micro-pores created by PLAMNs@PDA-AgNPs, indicating their safety. Both in vitro and in vivo tests confirmed antibacterial efficacy of PLAMNs@PDA-AgNPs.

Conclusions

In conclusion, the sustained antibacterial activity exhibited by PLAMNs@PDA-AgNPs offers a promising solution for addressing skin infections associated with MN applications, especially when compared to traditional MN-based biosensors. This advancement offers significant potential for the field of MN technology.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Data Availability

Data will be made available on request.

Abbreviations

AgNPs:

Silver Nanoparticle

CIP-HCl:

Ciprofloxacin Hydrochloride

H:

Hour

HCL:

Hydrogen Chloride

ISF:

Interstitial Fluid

KBr:

Potassium Bromide

LB:

Luria-Bertani

Min:

Minute

MNs:

Microneedles

PCL:

Polycaprolactone

PDA:

Polydopamine

DA:

Dopamine

PLAMNs:

Polylactic Acid Microneedles

PE:

Polyethylene

TEWL:

Transepidermal Water Loss

References

  1. Halder J, Gupta S, Kumari R, Gupta GD, Rai VK. Microneedle Array: Applications, Recent Advances, and Clinical Pertinence in Transdermal Drug Delivery. J Pharm Innov. 2021;16(3):558–65. https://doi.org/10.1007/s12247-020-09460-2.

    Article  PubMed  Google Scholar 

  2. Hao Y, Li W, Zhou XL, Yang F, Qian ZY. Microneedles-Based Transdermal Drug Delivery Systems: A Review. J Biomed Nanotechnol. 2017;13(12):1581–97. https://doi.org/10.1166/jbn.2017.2474.

    Article  CAS  PubMed  Google Scholar 

  3. Jamaledin RYC, Zare EN, Niu LN, Vecchione R, Chen G, Gu Z, Tay FR, Makvandi P. Advances in Antimicrobial Microneedle Patches for Combating Infections. Adv Mater. 2020;32(33):e2002129. https://doi.org/10.1002/adma.202002129.

    Article  CAS  PubMed  Google Scholar 

  4. Guillot AJ, Cordeiro AS, Donnelly RF, Garrigues TM, Melero A. Microneedle-based delivery: an overview of current applications and trends. Pharmaceutics. 2020;12(6):569. https://doi.org/10.3390/pharmaceutics12060569.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Prausnitz Mark R, Mitragotri Samir, Langer Robert. Current status and future potential of transdermal drug delivery. Nat Rev Drug Discov. 2004;3(2):115–24. https://doi.org/10.1038/nrd1304.

    Article  CAS  PubMed  Google Scholar 

  6. Zahra Faraji Rad PDPaGJD. An overview of microneedle applications, materials, and fabrication methods. Beilstein J Nanotechnol. 2021;12:1034–46. https://doi.org/10.3762/bjnano.12.77.

    Article  CAS  Google Scholar 

  7. Tucak A, Sirbubalo M, Hindija L, Rahić O, Hadžiabdić J, Muhamedagić K, Čekić A, Vranić E. Microneedles: characteristics, materials, production methods and commercial development. Micromachines. 2020;11(11):961. https://doi.org/10.3390/mi11110961.

  8. Bhatnagar S, Dave K, Venuganti VVK. Microneedles in the clinic. J Control Release. 2017;260:164–82. https://doi.org/10.1016/j.jconrel.2017.05.029.

    Article  CAS  PubMed  Google Scholar 

  9. Zhang Junyu, Zhang Xiaojing, Wei Xinwei, Xue Yingying, Wan Hao, Wang Ping. Recent advances in acoustic wave biosensors for the detection of disease-related biomarkers: A review. Anal Chim Acta. 2021;1164:338321. https://doi.org/10.1016/j.aca.2021.338321.

    Article  CAS  PubMed  Google Scholar 

  10. Yang Bin, Kong Jilie, Fang Xueen. Programmable CRISPR-Cas9 microneedle patch for long-term capture and real-time monitoring of universal cell-free DNA. Nat Commun. 2022;13(1):3999. https://doi.org/10.1038/s41467-022-31740-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Wang ZLJ, Seth A, Liu L, You M, Gupta P, Rathi P, Wang Y, Cao S, Jiang Q, Zhang X, Gupta R, Zhou Q, Morrissey JJ, Scheller EL, Rudra JS, Singamaneni S. Microneedle patch for the ultrasensitive quantification of protein biomarkers in interstitial fluid. Nat Biomed Eng. 2021;5(1):64–76. https://doi.org/10.1038/s41551-020-00672-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Teymourian HMC, Tehrani F, Vargas E, Aghavali R, Barfidokht A, Tangkuaram T, Mercier PP, Dassau E, Wang J. Microneedle-Based Detection of Ketone Bodies along with Glucose and Lactate: Toward Real-Time Continuous Interstitial Fluid Monitoring of Diabetic Ketosis and Ketoacidosis. Anal Chem. 2020;92(2):2291–300. https://doi.org/10.1021/acs.analchem.9b05109.

    Article  CAS  PubMed  Google Scholar 

  13. Liu GSKY, Wang Y, Luo Y, Fan X, Xie X, Yang BR, Wu MX. Microneedles for transdermal diagnostics: Recent advances and new horizons. Biomaterials. 2020;232:119740. https://doi.org/10.1016/j.biomaterials.2019.119740.

    Article  CAS  PubMed  Google Scholar 

  14. Zhang BL, Yang Y, Zhao ZQ, Guo XD. A gold nanoparticles deposited polymer microneedle enzymatic biosensor for glucose sensing. Electrochim Acta. 2020;358:136917. https://doi.org/10.1016/j.electacta.2020.136917.

    Article  CAS  Google Scholar 

  15. Barnum Lindsay, Samandari Mohamadmahdi, Schmidt Tannin A, Tamayol Ali. Microneedle arrays for the treatment of chronic wounds. Expert Opin Drug Deliv. 2020;17(12):1767–80. https://doi.org/10.1080/17425247.2020.1819787.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Yao SCJ, Wang Y, Zhao Y, Luo Y, Wang Y. Zn-MOF Encapsulated Antibacterial and Degradable Microneedles Array for Promoting Wound Healing. Adv Healthc Mater. 2021;10(12):e2100056. https://doi.org/10.1002/adhm.202100056.

    Article  CAS  PubMed  Google Scholar 

  17. Bhatnagar SSA, Cheerla KD, Gade SK, Garg P, Venuganti VVK. Corneal delivery of besifloxacin using rapidly dissolving polymeric microneedles. Drug Deliv Transl Res. 2018;8(3):473–83. https://doi.org/10.1007/s13346-017-0470-8.

    Article  CAS  PubMed  Google Scholar 

  18. Zhang TSB, Guo J, Wang M, Cui H, Mao H, Wang B, Yan F. Active pharmaceutical ingredient poly(ionic liquid)-based microneedles for the treatment of skin acne infection. Acta Biomater. 2020;115:136–47. https://doi.org/10.1016/j.actbio.2020.08.023.

    Article  CAS  PubMed  Google Scholar 

  19. Ventrelli LMSL, Barillaro G. Microneedles for Transdermal Biosensing: Current Picture and Future Direction. Adv Healthc Mater. 2015;4(17):2606–40. https://doi.org/10.1002/adhm.201500450.

    Article  CAS  PubMed  Google Scholar 

  20. Gittard SDNR, Jin C, Ovsianikov A, Chichkov BN, Monteiro-Riviere NA, Stafslien S, Chisholm B. Pulsed laser deposition of antimicrobial silver coating on Ormocer microneedles. Biofabrication. 2009;1(4):041001. https://doi.org/10.1088/1758-5082/1/4/041001.

    Article  CAS  PubMed  Google Scholar 

  21. Morrison ML, Buchanan RA, Liaw PK, Berry CJ, Brigmon RL, Riester L, Abernathy H, Jin C, Narayan RJ. Electrochemical and antimicrobial properties of diamondlike carbon-metal composite films. Diam Relat Mater. 2006;15(1):138–46. https://doi.org/10.1016/j.diamond.2005.08.031.

    Article  CAS  Google Scholar 

  22. Chew SWTZY, Cui M, Chang H, Zheng M, Wei S, Zhao W, Xu C. In Situ Generation of Zinc Oxide Nanobushes on Microneedles as Antibacterial Coating. SLAS Technol. 2019;24(2):181–7. https://doi.org/10.1177/2472630318812350.

    Article  CAS  PubMed  Google Scholar 

  23. Jain A, SailajaDuvvuri L, Farah S, Beyth N, Domb AJ, Khan W. Antimicrobial polymers. Advanced Healthcare Materials. 2014;3(12):1969–85. https://doi.org/10.1002/adhm.201400418.

    Article  CAS  PubMed  Google Scholar 

  24. Slavin YNAJ, Häfeli UO, Bach H. Metal nanoparticles: understanding the mechanisms behind antibacterial activity. J Nanobiotechnology. 2017;15(1):65. https://doi.org/10.1186/s12951-017-0308-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. González García LE, MacGregor MN, Visalakshan RM, Ninan N, Cavallaro AA, Trinidad AD, Zhao Y, Hayball AJD, Vasilev K. Self-sterilizing antibacterial silver-loaded microneedles. Chem Commun (Camb). 2018;55(2):171–4. https://doi.org/10.1039/c8cc06035e.

    Article  CAS  PubMed  Google Scholar 

  26. Yin IXZJ, Zhao IS, Mei ML, Li Q, Chu CH. The Antibacterial Mechanism of Silver Nanoparticles and Its Application in Dentistry. Int J Nanomedicine. 2020;15:2555–62. https://doi.org/10.2147/IJN.S246764.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Haider A, Kang I-K. Preparation of Silver Nanoparticles and Their Industrial and Biomedical Applications: A Comprehensive Review. Adv Mater Sci Eng. 2015;2015:1–16. https://doi.org/10.1155/2015/165257.

    Article  Google Scholar 

  28. Sureshkumar M, Siswanto DY, Chen Y-C, Lee C-K, Wang M-J. Antibacterial and biocompatible surfaces based on dopamine autooxidized silver nanoparticles. J Polym Sci B Polym Phys. 2013;51(4):303–10. https://doi.org/10.1002/polb.23212.

    Article  CAS  Google Scholar 

  29. Wang QL, Zhu DD, Chen Y, Guo XD. A fabrication method of microneedle molds with controlled microstructures. Mater Sci Eng C. 2016;665:135–42. https://doi.org/10.1016/j.msec.2016.03.097.

    Article  CAS  Google Scholar 

  30. Rithesh Raj D, Prasanth S, Vineeshkumar TV, Sudarsanakumar C. Surface plasmon resonance based fiber optic dopamine sensor using green synthesized silver nanoparticles. Sens Actuators B Chem. 2016;224:600–6. https://doi.org/10.1016/j.snb.2015.10.106.

    Article  CAS  Google Scholar 

  31. Das TK, Ganguly S, Bhawal P, Remanan S, Mondal S, Das NC. Mussel inspired green synthesis of silver nanoparticles-decorated: halloysite nanotube using dopamine: characterization and evaluation of its catalytic activity. Appl Nanosci. 2018;8:173–86. https://doi.org/10.1007/s13204-018-0658-3.

    Article  CAS  Google Scholar 

  32. Bagherzade G, Tavakoli MM, Namaei MH. Green synthesis of silver nanoparticles using aqueous extract of saffron (Crocus sativus L.) wastages and its antibacterial activity against six bacteria. Asian Pac J Trop Biomed. 2017;7(3):227–33. https://doi.org/10.1016/j.apjtb.2016.12.014.

    Article  Google Scholar 

  33. Fang Y, Hong C-Q, Chen F-R, Gui F-Z, You Y-X, Guan X, Pan X-H. Green synthesis of nano silver by tea extract with high antimicrobial activity. Inorg Chem Commun. 2021;132:1–5. https://doi.org/10.1016/j.inoche.2021.108808.

    Article  CAS  Google Scholar 

  34. Shu W, Heimark H, Bertollo N, Tobin DJ, O’Cearbhaill ED, Annaidh AN. Insights into the mechanics of solid conical microneedle array. Acta Biomater. 2021;135:403–13. https://doi.org/10.1016/j.actbio.2021.08.045.

    Article  CAS  PubMed  Google Scholar 

  35. Donnelly RF, Singh TRR, Woolfson AD. Microneedle-based drug delivery systems Microfabrication, drug delivery, and safety. Crit Rev Biochem Mol Biol. 2010;17(4):187–207. https://doi.org/10.3109/10717541003667798.

    Article  CAS  Google Scholar 

  36. Luo H, Gu C, Zheng W, Dai F, Wang X, Zheng Z. Facile synthesis of novel size-controlled antibacterial hybrid spheres using silver nanoparticles loaded with poly-dopamine spheres. R Soc Chem. 2015;5:13470–7. https://doi.org/10.1039/C4RA16469E.

    Article  CAS  Google Scholar 

  37. Shanmugam L, Feng X, Yang J. Enhanced interphase between thermoplastic matrix and UHMWPE fiber sized with CNT-modified polydopamine coating. Compos Sci Technol. 2019;174:212–20. https://doi.org/10.1016/j.compscitech.2019.03.001.

    Article  CAS  Google Scholar 

  38. Wang W, Zhang A, Liu L, Tian M, Zhang L. Dopamine-Induced Surface Functionalization for the Preparation of Al-Ag Bimetalic microspheres. J Electrochem Soc. 2011;158:D228–33. https://doi.org/10.1149/1.3551496.

    Article  CAS  Google Scholar 

  39. Alexander H, Brown S, Danby S, Flohr C. Research Techniques Made Simple Transepidermal Water Loss Measurement as a Research Tool. J Invest Dermatol. 2018;138:2295–300. https://doi.org/10.1016/j.jid.2018.09.001.

    Article  CAS  PubMed  Google Scholar 

  40. Chen J, Wang M, Ye Y, Yang Z, Ruan Z, Jin N. Fabrication of sponge-forming microneedle patch for rapidly sampling interstitial fluid for analysis. Biomed Microdevices. 2019;21(63):1–10. https://doi.org/10.1007/s10544-019-0413-x.

    Article  CAS  Google Scholar 

  41. Lasprilla AJR, Martinez GAR, Lunelli BH, Jardini AL, Filho RM. Poly-lactic acid synthesis for application in biomedical devices — A review. Biotechnology Advances. 2012;30:321–8. https://doi.org/10.1016/j.biotechadv.2011.06.019.

    Article  CAS  PubMed  Google Scholar 

  42. O Martin LA. Poly(lactic acid): plasticization and properties of biodegradable multiphase systems. Polym Sci Ser A Chem Phys. 2001;42(14):6209–19. https://doi.org/10.1016/S0032-3861(01)00086-6.

    Article  Google Scholar 

  43. Luo F, Fortenberry A, Ren J, Qiang Z. Recent progress in enhancing poly(Lactic Acid) stereocomplex formation for material property improvement. Front Chem. 2020;8:688. https://doi.org/10.3389/fchem.2020.00688.

  44. Paladini F, Pollini M. Antimicrobial Silver Nanoparticles for Wound Healing Appilcation: Progress and Future Trends. Materials. 2019;12(16):2540. https://doi.org/10.3390/ma12162540.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Kobayashi TVB, Kim DY, Kennedy EA, Jo JH, Shih HY, Truong A, Doebel T, Sakamoto K, Cui CY, Schlessinger D, Moro K, Nakae S, Horiuchi K, Zhu J, Leonard WJ, Kong HH, Nagao K. Homeostatic Control of Sebaceous Glands by Innate Lymphoid Cells Regulates Commensal Bacteria Equilibrium. Cell. 2019;176(9):982–97. https://doi.org/10.1016/j.cell.2018.12.031.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Zouboulis CC, Jourdan E, Picardo M. Acne is an inflammatory disease and alterations of sebum composition initiate acne lesions. Eur Acad Dermatol Venereol. 2014;28(5):527–32. https://doi.org/10.1111/jdv.12298.

    Article  CAS  Google Scholar 

Download references

Funding

This study was supported by National Natural Science Foundation of China (NO. 82001926) and Science and Technology Bureau of Putian (NO. 2021ZP01).

Author information

Authors and Affiliations

Authors

Contributions

Wenqin Zhang designed the experiment and wrote the manuscript. Xiaozhen Cai and Xinyi zhang analyzed the data. Danhong Zhu and Shiqi Zou Photo drew the figures. Jianmin Chen reviewed and revised the manuscript to determine the final version.

Corresponding author

Correspondence to Jianmin Chen.

Ethics declarations

Conflict of Interest

No potential conflict of interest was reported by the authors.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, W., Cai, X., Zhang, X. et al. AgNPs-Modified Polylactic Acid Microneedles: Preparation and In Vivo/In Vitro Antimicrobial Studies. Pharm Res 41, 93–104 (2024). https://doi.org/10.1007/s11095-023-03634-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-023-03634-6

Keywords

Navigation