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Physico-chemical Evaluation of Antiatherosclerotic Coronary Stent Coatings Based on Poly(lactic acid) Doped with Functionalized Fe@C Nanoparticles

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Abstract

High mortality associated with atherosclerosis necessitates the development of novel strategies for its treatment. Despite the widespread use and success of lipid-reducing drugs in therapy, they often come with unwanted side effects. One of the modern approaches for atherosclerosis treatment is using coronary stents with polymer coating and antiatherosclerotic agent, which can be released locally. Previously, our team demonstrated the benefits of composite coatings based on poly(lactic acid) (PLA) doped with Fe@C nanoparticles functionalized with C18 hydrophobic groups (C18-NPs). The presence of hydrophobic groups on the nanoparticles surface allows them to interact effectively with atherosclerotic plaque leading to its structural changes and destruction. Herein, the effect of functionalized nanoparticle content (from 0 to 10 wt.%) on the physicochemical properties of the composite PLA-based coatings (particularly, morphology, elemental composition, hydrophilicity, crystal structure, and adhesion to the substrate) is reported. It is demonstrated that the deposited coatings uniformly cover the surface of the model AISI 321H steel substrates with oxynitride layer regardless of the nanoparticle content. It was found that nanoparticle content had no effect on the PLA crystal structure. The formation of nanoparticle agglomerates and surface hydrophobization was observed for coatings with a nanoparticle content greater than 1 wt.%. The reported findings indicate that a nanoparticle content of 5 wt.% is optimal in terms of achieving a desirable combination of physicochemical characteristics and the ability to degrade atherosclerotic plaques.

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References 

  1. Björkegren, J. L. M., & Lusis, A. J. (2022). Atherosclerosis: Recent developments. Cell, 185(10), 1630–1645. https://doi.org/10.1016/j.cell.2022.04.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Weber, C., & Noels, H. (2011). Atherosclerosis: Current pathogenesis and therapeutic options. Nature Medicine, 17(11), 1410–1422. https://doi.org/10.1038/nm.2538

    Article  CAS  PubMed  Google Scholar 

  3. Falk, E., Shah, P. K., & Fuster, V. (1995). Coronary plaque disruption. Circulation, 92(3), 657–671. https://doi.org/10.1161/01.CIR.92.3.657

    Article  CAS  PubMed  Google Scholar 

  4. Ullah, M., Wahab, A., Khan, S. U., Zaman, U., Rehman, K. ur, Hamayun, S., … Refat, M. S. (2023). Stent as a novel technology for coronary artery disease and their clinical manifestation. Current Problems in Cardiology, 48(1), 101415. https://doi.org/10.1016/j.cpcardiol.2022.101415

  5. Beshchasna, N., Saqib, M., Kraskiewicz, H., Wasyluk, Ł., Kuzmin, O., Duta, O. C., … Andronescu, E. (2020). Recent advances in manufacturing innovative stents. Pharmaceutics, 12(4) 349. https://doi.org/10.3390/pharmaceutics12040349

  6. Zong, J., He, Q., Liu, Y., Qiu, M., Wu, J., & Hu, B. (2022). Advances in the development of biodegradable coronary stents: A translational perspective. Materials Today Bio, 16, 100368. https://doi.org/10.1016/j.mtbio.2022.100368

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Sheiban, I. (2008). Next-generation drug-eluting stents in coronary artery disease: Focus on everolimus-eluting stent (Xience V®). Vascular Health and Risk Management, 4(1), 31–38. https://doi.org/10.2147/vhrm.2008.04.01.31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Wang, H., Wang, Q., Hu, J., Zhang, R., Gao, T., Rong, S., & Dong, H. (2022). Global research trends in in-stent neoatherosclerosis: A CiteSpace-based visual analysis. Frontiers in Cardiovascular Medicine, 9. https://doi.org/10.3389/fcvm.2022.1025858

  9. Rodríguez, G., Fernández-Gutiérrez, M., Parra, J., López-Bravo, A., Molina, M., Duocastella, L., & San Román, J. (2012). Bioactive coatings for coronary stents: Modulation of cell proliferation by controlled release of anti-proliferative drugs. Journal of Bioactive and Compatible Polymers, 27(6), 550–564. https://doi.org/10.1177/0883911512465699

    Article  CAS  Google Scholar 

  10. Liu, P., Liu, Y., Li, P., Zhou, Y., Song, Y., Shi, Y., … Zhu, W. (2018). Rosuvastatin- and heparin-loaded poly(l-lactide-co-caprolactone) nanofiber aneurysm stent promotes endothelialization via vascular endothelial growth factor type A modulation. ACS Applied Materials & Interfaces, 10(48): 41012–41018. https://doi.org/10.1021/acsami.8b11714

  11. Borhani, S., Hassanajili, S., Ahmadi Tafti, S. H., & Rabbani, S. (2018). Cardiovascular stents: Overview, evolution, and next generation. Progress in Biomaterials, 7(3), 175–205. https://doi.org/10.1007/s40204-018-0097-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Yang, J., Zeng, Y., Zhang, C., Chen, Y.-X., Yang, Z., Li, Y., … Song, C.-X. (2013). The prevention of restenosis in vivo with a VEGF gene and paclitaxel co-eluting stent. Biomaterials, 34(6), 1635–1643. https://doi.org/10.1016/j.biomaterials.2012.11.006

  13. Barnes, P. J. (2011). Glucocorticosteroids: Current and future directions. British Journal of Pharmacology, 163(1), 29–43. https://doi.org/10.1111/j.1476-5381.2010.01199.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Prilepskii, A. Y., Serov, N. S., Kladko, D. V., & Vinogradov, V. V. (2020). Nanoparticle-based approaches towards the treatment of atherosclerosis. Pharmaceutics, 12(11), 1056. https://doi.org/10.3390/pharmaceutics12111056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Zhao, J., Mo, Z., Guo, F., Shi, D., Han, Q. Q., & Liu, Q. (2018). Drug loaded nanoparticle coating on totally bioresorbable PLLA stents to prevent in-stent restenosis. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 106(1), 88–95. https://doi.org/10.1002/jbm.b.33794

    Article  CAS  PubMed  Google Scholar 

  16. Wang, Y., Zhang, W., Zhang, J., Sun, W., Zhang, R., & Gu, H. (2013). Fabrication of a novel polymer-free nanostructured drug-eluting coating for cardiovascular stents. ACS Applied Materials & Interfaces, 5(20), 10337–10345. https://doi.org/10.1021/am403365j

    Article  CAS  Google Scholar 

  17. Ge, S., Xi, Y., Du, R., Ren, Y., Xu, Z., Tan, Y., … Wang, G. (2019). Inhibition of in-stent restenosis after graphene oxide double-layer drug coating with good biocompatibility. Regenerative Biomaterials, 6(5), 299–309. https://doi.org/10.1093/rb/rbz010

  18. Liu, J., Guo, X., Zhao, Z., Li, B., Qin, J., Peng, Z., … Lu, X. (2020). Fe3S4 nanoparticles for arterial inflammation therapy: Integration of magnetic hyperthermia and photothermal treatment. Applied Materials Today, 18, 100457. https://doi.org/10.1016/j.apmt.2019.100457

  19. Hossaini Nasr, S., & Huang, X. (2021). Nanotechnology for targeted therapy of atherosclerosis. Frontiers in Pharmacology, 12. https://doi.org/10.3389/fphar.2021.755569

  20. DiStasio, N., Lehoux, S., Khademhosseini, A., & Tabrizian, M. (2018). The multifaceted uses and therapeutic advantages of nanoparticles for atherosclerosis research. Materials, 11(5), 754. https://doi.org/10.3390/ma11050754

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  21. Akhmedov, S., Afanasyev, S., Beshchasna, N., Trusova, M., Stepanov, I., Rebenkova, M., … Kozlov, B. (2022). Effect of chemically modified carbon-coated iron nanoparticles on the structure of human atherosclerotic plaques ex vivo and on adipose tissue in chronic experiment in vivo. International Journal of Molecular Sciences, 23(15), 8241. https://doi.org/10.3390/ijms23158241

  22. Rykowska, I., Nowak, I., & Nowak, R. (2020). Drug-eluting stents and balloons—Materials, structure designs, and coating techniques: A review. Molecules, 25(20), 4624. https://doi.org/10.3390/molecules25204624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Renò, F., Traina, V., & Cannas, M. (2007). Haemocompatibility of vitamin-E-enriched poly(D, L-lactic acid). Journal of Biomaterials Science, Polymer Edition, 18(6), 785–797. https://doi.org/10.1163/156856207781034098

    Article  PubMed  Google Scholar 

  24. Sun, Z., Pichugin, V. F., Evdokimov, K. E., Konishchev, M. E., Syrtanov, M. S., Kudiiarov, V. N., … Tverdokhlebov, S. I. (2020). Effect of nitrogen-doping and post annealing on wettability and band gap energy of TiO2 thin film. Applied Surface Science, 500, 144048. https://doi.org/10.1016/j.apsusc.2019.144048

  25. Ermakov, A. E., Uimin, M. A., Lokteva, E. S., Mysik, A. A., Kachevskii, S. A., Turakulova, A. O., … Lunin, V. V. (2009). The synthesis, structure, and properties of carbon-containing nanocomposites based on nickel, palladium, and iron. Russian Journal of Physical Chemistry A, 83(7), 1187–1193. https://doi.org/10.1134/S0036024409070243

  26. Akhmedov, S., Afanasyev, S., Trusova, M., Postnikov, P., Rogovskaya, Y., Grakova, E., … Popov, S. (2021). Chemically modified biomimetic carbon-coated iron nanoparticles for stent coatings: In vitro cytocompatibility and in vivo structural changes in human atherosclerotic plaques. Biomedicines, 9(7), 802. https://doi.org/10.3390/biomedicines9070802

  27. Kim, S. M., Park, S.-B., Bedair, T. M., Kim, M.-H., Park, B. J., Joung, Y. K., & Han, D. K. (2017). The effect of solvents and hydrophilic additive on stable coating and controllable sirolimus release system for drug-eluting stent. Materials Science and Engineering: C, 78, 39–46. https://doi.org/10.1016/j.msec.2017.04.024

    Article  CAS  PubMed  Google Scholar 

  28. Amani, H., Arzaghi, H., Bayandori, M., Dezfuli, A. S., Pazoki‐Toroudi, H., Shafiee, A., & Moradi, L. (2019). Controlling cell behavior through the design of biomaterial surfaces: A focus on surface modification techniques. Advanced Materials Interfaces, 6(13). https://doi.org/10.1002/admi.201900572

  29. Xu, C., Yang, F., Wang, S., & Ramakrishna, S. (2004). In vitro study of human vascular endothelial cell function on materials with various surface roughness. Journal of Biomedical Materials Research, 71A(1), 154–161. https://doi.org/10.1002/jbm.a.30143

    Article  CAS  Google Scholar 

  30. Sun, Z., Evdokimov, K. E., Konishchev, M. E., Kuzmin, O. S., & Pichugin, V. F. (2019). Effect of post annealing on properties of N-doped TiO 2 films deposited by reactive magnetron sputtering. Journal of Physics: Conference Series, 1281(1), 012083. https://doi.org/10.1088/1742-6596/1281/1/012083

    Article  CAS  Google Scholar 

  31. Surovtseva, M. A., Poveschenko, O. V., Kuzmin, O. S., Kim, I. I., Kozhukhov, A. S., Bondarenko, N. A., … Yu. Zhuravleva, I. (2022). Titanium oxide– and oxynitride–coated nitinol: Effects of surface structure and composition on interactions with endothelial cells. Applied Surface Science, 578, 152059. https://doi.org/10.1016/j.apsusc.2021.152059

  32. Arbeiter, D., Reske, T., Teske, M., Bajer, D., Senz, V., Schmitz, K.-P., … Oschatz, S. (2021). Influence of drug incorporation on the physico-chemical properties of poly(l-lactide) implant coating matrices—A systematic study. Polymers, 13(2), 292. https://doi.org/10.3390/polym13020292

  33. Huang, W., Mei, D., Zhang, J., Chen, D., Li, J., Wang, L., … Guan, S. (2021). Improved corrosion resistance and cytocompatibility of Mg–Zn–Y–Nd alloy by the electrografted polycaprolactone coating. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 629, 127471. https://doi.org/10.1016/j.colsurfa.2021.127471

  34. Liu, M., Zhang, Y., & Zhou, C. (2013). Nanocomposites of halloysite and polylactide. Applied Clay Science, 75–76, 52–59. https://doi.org/10.1016/j.clay.2013.02.019

    Article  CAS  ADS  Google Scholar 

  35. Filimonov, V. D., Trusova, M., Postnikov, P., Krasnokutskaya, E. A., Lee, Y. M., Hwang, H. Y., … Chi, K.-W. (2008). Unusually stable, versatile, and pure arenediazonium tosylates: Their preparation, structures, and synthetic applicability. Organic Letters, 10(18), 3961–3964. https://doi.org/10.1021/ol8013528

  36. Zhang, J., Tsuji, H., Noda, I., & Ozaki, Y. (2004). Weak intermolecular interactions during the melt crystallization of poly(l-lactide) investigated by two-dimensional infrared correlation spectroscopy. The Journal of Physical Chemistry B, 108(31), 11514–11520. https://doi.org/10.1021/jp048308q

    Article  CAS  Google Scholar 

  37. Vasanthan, N., & Ly, O. (2009). Effect of microstructure on hydrolytic degradation studies of poly (l-lactic acid) by FTIR spectroscopy and differential scanning calorimetry. Polymer Degradation and Stability, 94(9), 1364–1372. https://doi.org/10.1016/j.polymdegradstab.2009.05.015

    Article  CAS  Google Scholar 

  38. Zhang, J., Duan, Y., Sato, H., Tsuji, H., Noda, I., Yan, S., & Ozaki, Y. (2005). Crystal modifications and thermal behavior of poly(l-lactic acid) revealed by infrared spectroscopy. Macromolecules, 38(19), 8012–8021. https://doi.org/10.1021/ma051232r

    Article  CAS  ADS  Google Scholar 

  39. Pan, P., Kai, W., Zhu, B., Dong, T., & Inoue, Y. (2007). Polymorphous crystallization and multiple melting behavior of poly(l-lactide): Molecular weight dependence. Macromolecules, 40(19), 6898–6905. https://doi.org/10.1021/ma071258d

    Article  CAS  ADS  Google Scholar 

  40. Wu, Y., Simonovsky, F. I., Ratner, B. D., & Horbett, T. A. (2005). The role of adsorbed fibrinogen in platelet adhesion to polyurethane surfaces: A comparison of surface hydrophobicity, protein adsorption, monoclonal antibody binding, and platelet adhesion. Journal of Biomedical Materials Research Part A, 74A(4), 722–738. https://doi.org/10.1002/jbm.a.30381

    Article  CAS  Google Scholar 

  41. Jin, J., Zhou, S., & Duan, H. (2018). Preparation and properties of heat treated FHA@PLA composition coating on micro-oxidized AZ91D magnesium alloy. Surface and Coatings Technology, 349, 50–60. https://doi.org/10.1016/j.surfcoat.2018.05.043

    Article  CAS  Google Scholar 

  42. Cai, H., Dave, V., Gross, R. A., & McCarthy, S. P. (1996). Effects of physical aging, crystallinity, and orientation on the enzymatic degradation of poly(lactic acid). Journal of Polymer Science, Part B: Polymer Physics, 34(16), 2701–2708. https://doi.org/10.1002/(SICI)1099-0488(19961130)34:16%3c2701::AID-POLB2%3e3.0.CO;2-S

    Article  ADS  Google Scholar 

  43. Guinault, A., Sollogoub, C., Domenek, S., Grandmontagne, A., & Ducruet, V. (2010). Influence of crystallinity on gas barrier and mechanical properties of PLA food packaging films. International Journal of Material Forming, 3(S1), 603–606. https://doi.org/10.1007/s12289-010-0842-9

    Article  Google Scholar 

  44. Biggs, D. L., Lengsfeld, C. S., Hybertson, B. M., Ng, K., Manning, M. C., & Randolph, T. W. (2003). In vitro and in vivo evaluation of the effects of PLA microparticle crystallinity on cellular response. Journal of Controlled Release, 92(1–2), 147–161. https://doi.org/10.1016/S0168-3659(03)00325-0

    Article  CAS  PubMed  Google Scholar 

  45. Tong, P., Chen, L., Sun, X., Li, H., Feng, Y., Li, J., & Guan, S. (2023). Surface modification of biodegradable magnesium alloy with poly (L-lactic acid) and sulfonated hyaluronic acid nanoparticles for cardiovascular application. International Journal of Biological Macromolecules, 237, 124191. https://doi.org/10.1016/j.ijbiomac.2023.124191

    Article  CAS  PubMed  Google Scholar 

  46. Vrsaljko, D., Grčić, I., Guyon, C., Schelcher, G., & Tatoulian, M. (2016). Designing Hydrophobicity of the PLA polymer blend surfaces by ICP etching. Plasma Processes and Polymers, 13(9), 869–878. https://doi.org/10.1002/ppap.201500218

    Article  CAS  Google Scholar 

  47. Meding, J., Urich, M., Licha, K., Reinhardt, M., Misselwitz, B., Fayad, Z. A., & Weinmann, H.-J. (2007). Magnetic resonance imaging of atherosclerosis by targeting extracellular matrix deposition with Gadofluorine M. Contrast Media & Molecular Imaging, 2(3), 120–129. https://doi.org/10.1002/cmmi.137

    Article  CAS  Google Scholar 

  48. Gong, X., Cheng, C., Tang, C. Y., Law, W.-C., Lin, X., Chen, Y., … Rao, N. (2019). Crystallization behavior of polylactide matrix under the influence of nano-magnetite. Polymer Engineering & Science, 59(3), 608–615. https://doi.org/10.1002/pen.24976

  49. Guchait, A., Saxena, A., Chattopadhyay, S., & Mondal, T. (2022). Influence of nanofillers on adhesion properties of polymeric composites. ACS Omega, 7(5), 3844–3859. https://doi.org/10.1021/acsomega.1c05448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Coatings characterization was financially supported by the Russian Science Foundation (project number 21-74-30016). This research was carried out using the equipment of the CSU NMNT TPU, supported by the RF MES project #075-15-2021-710. Some part of this research was carried out using the core facilities of TPU’s “Physical and chemical methods of analysis, the Common Use Center (CUC),” Analytical Center of the Tomsk Polytechnic University, and the Resource Center “Materials Science Shared Center,” part of the “Tomsk Regional Common Use Center (TRCUC)” of Tomsk State University. The authors thank Prof. Ermakov for the supplied Fe@C nanoparticles.

Funding

This research was funded by the Russian Foundation for Basic Research (RFBR), grant number 20–53-76012.

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Conceptualization: Sh.A., S.T., M.T.; methodology: S.G.; formal analysis: S.G., S.T.; investigation: S.G., M.K., K.E., T.T.H.; resources: S.T., E.B.; data curation: S.G.; writing—original draft preparation: S.G.; visualization: S.G.; supervision: S.T.; project administration: S.T.; funding acquisition: S.T. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Sergei I. Tverdokhlebov.

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Goreninskii, S.I., Konishchev, M.E., Bolbasov, E.N. et al. Physico-chemical Evaluation of Antiatherosclerotic Coronary Stent Coatings Based on Poly(lactic acid) Doped with Functionalized Fe@C Nanoparticles. BioNanoSci. 14, 447–456 (2024). https://doi.org/10.1007/s12668-023-01272-1

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