Grafted poly (vinyl alcohol) functionalized by folic acid and its transdermal microneedles

Polymer Bulletin (2021)Cite this article

Abstract

A well-soluble grafted polymer of poly (vinyl alcohol) (PVA) used to fabricate dissolved microneedles was achieved through classic Michael addition and the functionalization of folate-targeted ligand. FTIR, Raman spectrum and 1H-NMR characterization ascertained the microstructure of resulted polymer. XPS analysis further confirmed the reasonability of analytic structure as well as the functionalized rate of folate of the modified PVA. Using the synthetic polymer to fabricate microneedles patch which was only a matter of 10% (w/w) concentration could accomplish, and the gained patch displayed decent insertion capability of porcine cadaver skin and the inserted microneedles emerged obviously a dissolved phenomenon within 1 min. Meanwhile, the left traces on surface of the skin recovered about 15 min after the patch removal, implying a little invasiveness to skin. The release of insulin-loaded microneedles exhibited burst release in the initial phase and then reduced gradually, and the insulin loaded in the needles of patch might release totally within 1 h, revealing the functionalized grafted polymer could be used as a well material for fabrication dissolving microneedles.

This is a preview of subscription content, access via your institution.

We’re sorry, something doesn't seem to be working properly.

Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

References

  1. 1.

    Choy YB, Prausnitz MR (2011) The rule of five for non-oral routes of drug delivery: ophthalmic. Inhal Transdermal Pharm Res 28(5):943–948. https://doi.org/10.1007/s11095-010-0292-6

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Donnelly RF, Singh TRR, Woolfson AD (2010) Microneedle-based drug delivery systems: Microfabrication, drug delivery, and safety. Drug Deliv 17(4):187–207. https://doi.org/10.3109/10717541003667798

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Lee JY, Park SH, Seo IH et al (2015) Rapid and repeatable fabrication of high A/R silk fibroin microneedles using thermally-drawn micromolds. Eur J Pharm Biopharm 94:11–19. https://doi.org/10.1016/j.ejpb.2015.04.024

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Yang S, Feng Y, Zhang L, Chen N, Yuan W, Jin T (2012) A scalable fabrication process of polymer microneedles. Int J Nanomed 7:1415–1422. https://doi.org/10.2147/IJN.S28511

    CAS  Article  Google Scholar 

  5. 5.

    Cao Y, Tao Y, Zhou Y et al (2016) Development of sinomenine hydrochloride-loaded polyvinylalcohol/maltose microneedle for transdermal delivery. J Drug Deliv Sci Tech 35:1–7. https://doi.org/10.1016/j.jddst.2016.06.007

    CAS  Article  Google Scholar 

  6. 6.

    Chen MC, Ling MH, Kusuma SJ (2015) Poly-γ-glutamic acid microneedles with a supporting structure design as a potential tool for transdermal delivery of insulin. Acta Biomater 24:106–116. https://doi.org/10.1016/j.actbio.2015.06.021

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    McGrath MG, Vucen S, Vrdoljak A, Kelly A, O’Mahony C, Crean AM, Moore A (2014) Production of dissolvable microneedle using an atomised spray process: effect of microneedle composition on skin penetration. Eur J Pharm Biopharm 86(2):200–211. https://doi.org/10.1016/j.ejpb.2013.04.023

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Lee IC, Wu YC, Tsai SW et al (2017) Fabrication of two-layer dissolving polyvinylpyrrolidone microneedles with different molecular weights for in vivo insulin transdermal delivery. RSC Adv 7(9):5067–5075. https://doi.org/10.1039/C6RA27476E

    CAS  Article  Google Scholar 

  9. 9.

    Li G, Badkar A, Nema S et al (2009) In vitro transdermal delivery of therapeutic antibodies using maltose microneedles. Int J Pharm 368(1–2):109–115. https://doi.org/10.1016/j.ijpharm.2008.10.008

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Lee JW, Park JH, Prausnitz MR (2008) Dissolving microneedles for transdermal drug delivery. Biomaterials 29(13):2113–2124. https://doi.org/10.1016/j.biomaterials.2007.12.048

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Liu S, Jin MN, Quan YS et al (2012) The development and characteristics of novel microneedle arrays fabricated from hyaluronic acid, and their application in the transdermal delivery of insulin. J Control Release 161(3):933–941. https://doi.org/10.1016/j.jconrel.2012.05.030

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Hirobe S, Azukizawa H, Hanafusa T, Matsuo K, Quan YS, Kamiyama F, Katayama I, Okada N, Nakagawa S (2015) Clinical study and stability assessment of a novel transcutaneous influenza vaccination using a dissolving microneedle patch. Biomaterials 57:50–58. https://doi.org/10.1016/j.biomaterials.2015.04.007

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Miyano T, Tobinaga Y, Kanno T et al (2005) Sugar micro needles as transdermic drug delivery system. Biomed Microdevices 7(3):185–188. https://doi.org/10.1007/s10544-005-3024-7

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Ito Y, Hagiwara E, Saeki A et al (2006) Feasibility of microneedles for percutaneous absorption of insulin. Eur J Pharm Sci 29(1):82–88. https://doi.org/10.1016/j.ejps.2006.05.011

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Donnelly RF, Morrow DIJ, Singh TRR et al (2009) Processing difficulties and instability of carbohydrate microneedle arrays. Drug Dev Ind Pharm 35(10):1242–1254. https://doi.org/10.1080/03639040902882280

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Nguyen HX, Dasht BB, Yujin K et al (2018) Poly (vinyl alcohol) microneedles: Fabrication, characterization, and application for transdermal drug delivery of doxorubicin. Eur J Pharm Biopharm 129:88–103. https://doi.org/10.1016/j.ejpb.2018.05.017

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Ma J, Yin X, Xiao H et al (2016) Functional modification of poly(vinyl alcohol) by copolymerizing with a hydrophobic cationic double alkyl-substituted monomer. J Appl Polym Sci. https://doi.org/10.1002/app.43888

    Article  Google Scholar 

  18. 18.

    Amodwala S, Kumar P, Thakkar HP (2017) Statistically optimized fast dissolving microneedle transdermal patch of meloxicam: a patient friendly approach to manage arthritis. Eur J Pharm Sci 104:114–123. https://doi.org/10.1016/j.ejps.2017.04.001

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Lee IC, He JS, Tsai MT et al (2014) Fabrication of a novel partially dissolving polymer microneedle patch for transdermal drug delivery. J Mat Chem B 3:276–285. https://doi.org/10.1039/C4TB01555J

    CAS  Article  Google Scholar 

  20. 20.

    Lau S, Fei J, Liu H et al (2017) Multilayered pyramidal dissolving microneedle patches with flexible pedestals for improving effective drug delivery. J Control Release 265:113–119. https://doi.org/10.1016/j.jconrel.2016.08.031

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Caló E, de Barros JMS, Fernández-Gutiérrez M et al (2016) Antimicrobial hydrogels based on autoclaved poly(vinyl alcohol) and poly(methyl vinyl ether-alt-maleic anhydride) mixtures for wound care applications. RSC Adv 6(60):55211–55219. https://doi.org/10.1039/C6RA08234C

    CAS  Article  Google Scholar 

  22. 22.

    Bhadra J, Al-Thani NJ, Madi NK et al (2017) Effects of aniline concentrations on the electrical and mechanical properties of polyaniline polyvinyl alcohol blends. Arab J Chem 10(5):664–672. https://doi.org/10.1016/j.arabjc.2015.04.017

    CAS  Article  Google Scholar 

  23. 23.

    Ita K (2017) Dissolving microneedles for transdermal drug delivery: Advances and challenges. Biomed Pharmacother 93:1116–1127. https://doi.org/10.1016/j.biopha.2017.07.019

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Ohira Y, Horii F, Nakaoki T (2001) Conformational changes of the noncrystalline chains for syndiotactic polypropylene as a function of temperature: correlations with the crystallizations of form I and form III. Macromolecules 34(6):1655–1662. https://doi.org/10.1021/ma0014564

    CAS  Article  Google Scholar 

  25. 25.

    Sato T, Okaya T (1992) Characterization and physical properties of low molecular weight poly(vinyl acetate) and poly(vinyl alcohol). Polym J 24(9):849–856. https://doi.org/10.1295/polymj.24.849

    CAS  Article  Google Scholar 

  26. 26.

    Dicharry RM, Ye P, Saha G et al (2006) Wheat gluten-thiolated poly(vinyl alcohol) blends with improved mechanical properties. Biomacromol 7(10):2837–2844. https://doi.org/10.1021/bm060432n

    CAS  Article  Google Scholar 

  27. 27.

    Lejardi A, Etxeberria A, Meaurio E, Sarasua JR (2012) Novelpoly(vinyl alcohol)-g-poly(hydroxy acid) copolymers: synthesis and characterization. Polymer 53(1):50–59. https://doi.org/10.1016/j.polymer.2011.11.029

    CAS  Article  Google Scholar 

  28. 28.

    Heaysman CL, Phillips GJ, Lloyd AW et al (2016) Synthesis and characterisation of cationic quaternary ammonium-modified polyvinyl alcohol hydrogel beads as a drug delivery embolisation system. J Mater Sci-Mater Med 27(3):53.1-53.10. https://doi.org/10.1007/s10856-015-5637-6

    CAS  Article  Google Scholar 

  29. 29.

    Lei CT, Wang Q, Li L (2009) Effect of interactions between poly(vinyl alcohol) and urea on the water solubility of poly(vinyl alcohol). J Appl Polym Sci 114(1):517–523. https://doi.org/10.1002/app.30504

    CAS  Article  Google Scholar 

  30. 30.

    Liu M, Xu W, Xu LJ et al (2005) Synthesis and biological evaluation of diethylenetriamine pentaacetic acid-polyethylene glycol-folate: a new folate-derived, 99mTc-based radiopharmaceutical. Bioconjug Chem 6(5):1126–1132. https://doi.org/10.1016/j.powtec.2008.02.018

    CAS  Article  Google Scholar 

  31. 31.

    Xing HZ (2013) Preparation and characterization of folate-decorated chitosan microspheres as a sustained-release drugs carrier. Adv Mater Res 684:57–62. https://doi.org/10.4028/www.scientific.net/amr.684.57

    Article  Google Scholar 

  32. 32.

    Li Y, Xie C, Liao Z, Zhu J (2014) Fabrication and strength test of micro needle array based on molding technology. Nanotechnol Precis Eng 12(3):194–201. https://doi.org/10.13494/j.npe.20130101

    CAS  Article  Google Scholar 

  33. 33.

    Bulut E, Şanlı O (2014) Novel ionically crosslinked acrylamide-grafted poly(vinyl alcohol)/sodium alginate/sodium carboxymethyl cellulose pH-sensitive microspheres for delivery of Alzheimer’s drug donepezil hydrochloride: preparation and optimization of release conditions. Artif Cells Nano Biotechnol 44(2):431–442. https://doi.org/10.3109/21691401.2014.962741

    CAS  Article  Google Scholar 

  34. 34.

    Prabaharan M, Grailer JJ, Pilla S et al (2009) Folate-conjugated amphiphilic hyperbranched block copolymers based on Boltorn® H40, poly(l-lactide) and poly(ethylene glycol) for tumor-targeted drug delivery. Biomaterials 30(16):3009–3019. https://doi.org/10.1016/j.biomaterials.2009.02.011

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Coyne J, Davis B, Kauffman D et al (2017) Polymer microneedle mediated local aptamer delivery for blocking the function of vascular endothelial growth factor. Acs Biomater Sci Eng 3(12):3395. https://doi.org/10.1021/acsbiomaterials.7b00718

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Yu W, Jiang G, Zhang Y et al (2017) Polymer microneedles fabricated from alginate and hyaluronate for transdermal delivery of insulin. Mater Sci Eng C 80(11):187–196. https://doi.org/10.1016/j.msec.2017.05.143

    CAS  Article  Google Scholar 

  37. 37.

    Lee IC, Lin WM, Shu JC et al (2016) Formulation of two-layer dissolving polymeric microneedle patches for insulin transdermal delivery in diabetic mice. J Biomed Mater Res Part A 105(1):84–93. https://doi.org/10.1002/jbm.a.35869

    CAS  Article  Google Scholar 

  38. 38.

    Yamini D, Devanand Venkatasubbu G, Kumar J et al (2014) Raman scattering studies on PEG functionalized hydroxyapatite nanoparticles. Spectroc Acta Pt A-Molec Biomolec Spectr 117:299–303. https://doi.org/10.1016/j.saa.2013.07.064

    CAS  Article  Google Scholar 

  39. 39.

    Lu Y, Jing R, Kong QM et al (2013) Solid state grafting copolymerization of acrylamide onto poly(vinyl alcohol) initiated by redox system. J Appl Polym Sci 131(4):1001–1007. https://doi.org/10.1002/app.39938

    CAS  Article  Google Scholar 

  40. 40.

    Bajpai AK, Vishwakarma A, Bajpai J (2018) Synthesis and characterization of amoxicillin loaded poly (vinyl alcohol)-g-poly (acrylamide) (PVA-g-PAM) hydrogels and study of swelling triggered release of antibiotic drug. Polym Bull. https://doi.org/10.1007/s00289-018-2536-2

    Article  Google Scholar 

  41. 41.

    Jang L, Yang TL, Peng LL et al (2015) Acrylamide modified poly(vinyl alcohol): crystalline and enhanced water solubility. RSC Adv 5:86598–86605. https://doi.org/10.1039/c5ra18437a

    Article  Google Scholar 

  42. 42.

    Ke CJ, Lin YJ, Hu YC et al (2012) Multidrug release based on microneedle arrays filled with pH-responsive PLGA hollow microspheres. Biomaterials 33(20):5156–5165. https://doi.org/10.1016/j.biomaterials.2012.03.056

    CAS  Article  PubMed  Google Scholar 

  43. 43.

    Liu WJ, Liu Q, Guo WJ, Yang M, Wang KJ, Wu FH (2019) Release behavior of folic acid grafted hollow hydroxyapatite as drug carrier. Adv Polym Tech 2019:1–9. https://doi.org/10.1155/2019/9562437

    CAS  Article  Google Scholar 

  44. 44.

    Yu YD, Zhu YJ, Qi C, Jiang YY, Li H, Wu J (2017) Hydroxyapatite nanorod-assembled porous hollow polyhedral as drug/protein carriers. J Colloid Interf Sci 496:416–424. https://doi.org/10.1016/i.jcis.2017.02.041

    CAS  Article  Google Scholar 

  45. 45.

    Sui ZY, Cui Y, Zhu JH, Han BH (2013) Preparation of three-dimensional graphene oxide−polyethylenimine porous materials as dye and gas adsorbents. ACS Appl Mater Interfaces 5:9172–9179. https://doi.org/10.1021/am402661t

    CAS  Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was performed on the Institute of Pharmaceutical Innovation, Shanghai Institute of Technology, and Dr. Yigui Li and colleagues, College of Science, provided the help of polydimethylsiloxane mold. The size is height × interspace × tips = 532 × 277 × 167, and 200 pinholes (20×10).

Funding

This work was financially supported by the National Natural Science Foundation of China (NO. 21672151) and Collaborative Innovation Fund of Shanghai Institute of Technology (NO. 39120K178030, 10120K208042).

Author information

Affiliations

  1. School of Chemical and Environmental Engineering, Shanghai Institute of Technology, 100 Haiquan Road, Shanghai, 201418, China

    Weijun Liu, Wenjing Guo, Mei Yang, Xiaoduo Zhang & Fanhong Wu

Authors
  1. Weijun Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wenjing Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mei Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaoduo Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fanhong Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Weijun Liu.

Ethics declarations

Conflict of interest

The authors declare that there are no conflict of interest.

Additional information

Publisher's Note

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

Supplementary information

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 15 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Liu, W., Guo, W., Yang, M. et al. Grafted poly (vinyl alcohol) functionalized by folic acid and its transdermal microneedles. Polym. Bull. (2021). https://doi.org/10.1007/s00289-021-03535-x

Download citation

Keywords

  • Microneedles
  • Grafted polymer
  • Modification
  • Poly (vinyl alcohol)
  • Functionalization