Advertisement

S2P peptide-conjugated PLGA-Maleimide-PEG nanoparticles containing Imatinib for targeting drug delivery to atherosclerotic plaques

  • Mehdi Esfandyari-Manesh
  • Masoome Abdi
  • Azita Hajhossein Talasaz
  • Seyedeh Masoumeh Ebrahimi
  • Fatemeh Atyabi
  • Rassoul DinarvandEmail author
Research article
  • 21 Downloads

Abstract

Background

Imatinib is a platelet-derived growth factor receptor (PDGFR) inhibitor with very low water solubility. Previous studies in atherosclerosis have shown that PDGFR activity has an egregious effect on vascular disease and progression of atherosclerosis. Specific ligands of atherosclerotic plaques can be used for targeting of nanoparticles. Studies in atherosclerosis proved that stabilin-2 is a glycoprotein which exists abundantly in atherosclerotic plaques and it is produced from both macrophages and endothelial cells.

Objectives

The objective of this study is the targeting drug delivery to atherosclerotic plaques by using imatinib-loaded nanoparticles modified by S2P peptide.

Methods

The imatinib-loaded nanoparticles were fabricated through a modified emulsion/solvent evaporation technique. After fabricating PLGA nanoparticles, maleimide PEG was used as linker between PLGA nanoparticles and S2P peptide. Because of presence cysteine in both side of S2P peptide, maleimide formed a thiolether linkage by thiol group of cysteine. Then the physicochemical analysis like H-NMR, FT-IR, DSC, SEM, particle size, zeta potential, and drug release were studied.

Results

Stabilin-2 peptide with sequence of CRTLTVRKC is a specific ligand to stabilin-2, so it was synthesized for using as the targeting agent for atherosclerosis. S2P peptide conjugation to the surface of nanoparticles was proved by H-NMR and FT-IR, and the percentage of S2P peptide in nanoparticles was 1.3%. The final nanoparticles were spherical and their size were 183 nm. The loading capacity of the imatinib-loaded nanoparticles was 5.05%. The sustained release profile was observed for peptide targeted nanoparticles.

Conclusion

The chosen method was simple, reproducible, and specific in peptide conjugation of nanoparticles for targeting delivery to atherosclerotic regions.

Graphical abstract

.

Keywords

Nanomedicine Surface conjugation S2P peptide Imatinib Atherosclerosis 

Notes

Acknowledgements

The authors are grateful to Nanotechnology Research Center of Tehran University of Medical Sciences (Tehran, Iran) for financial support.

Compliance with ethical standards

Conflict of interest

The authors report no conflicts of interest in this work.

References

  1. 1.
    Lee GY, Kim J-H, Oh GT, Lee B-H, Kwon IC, Kim I-S. Molecular targeting of atherosclerotic plaques by a stabilin-2-specific peptide ligand. J Control Release. 2011;155(2):211–7.CrossRefGoogle Scholar
  2. 2.
    Hansen KJ, Edwards MS, Craven TE, Cherr GS, Jackson SA, Appel RG, et al. Prevalence of renovascular disease in the elderly: a population-based study. J Vasc Surg. 2002;36(3):443–51.CrossRefGoogle Scholar
  3. 3.
    Douma K, Prinzen L, Slaaf DW, Reutelingsperger CP, Biessen EA, Hackeng TM, et al. Nanoparticles for optical molecular imaging of atherosclerosis. Small. 2009;5(5):544–57.CrossRefGoogle Scholar
  4. 4.
    Coppinger JA, Cagney G, Toomey S, Kislinger T, Belton O, McRedmond JP, et al. Characterization of the proteins released from activated platelets leads to localization of novel platelet proteins in human atherosclerotic lesions. Blood. 2004;103(6):2096–104.CrossRefGoogle Scholar
  5. 5.
    Jandt E, Mutschke O, Mahboobi S, Uecker A, Platz R, Berndt A, et al. Stent-based release of a selective PDGF-receptor blocker from the bis-indolylmethanon class inhibits restenosis in the rabbit animal model. Vasc Pharmacol. 2010;52(1):55–62.CrossRefGoogle Scholar
  6. 6.
    Masuda S, Nakano K, Funakoshi K, Zhao G, Meng W, Kimura S, et al. Imatinib mesylate-incorporated nanoparticle-eluting stent attenuates in-stent neointimal formation in porcine coronary arteries. J Atheroscler Thromb. 2011;18(12):1043–53.CrossRefGoogle Scholar
  7. 7.
    Mahdaviani P, Bahadorikhalili S, Navaei-Nigjeh M, Vafaei SY, Esfandyari-Manesh M, Abdolghaffari AH, et al. Peptide functionalized poly ethylene glycol-poly caprolactone nanomicelles for specific cabazitaxel delivery to metastatic breast cancer cells. Mater Sci Eng C. 2017;80:301–12.CrossRefGoogle Scholar
  8. 8.
    Esfandyari-Manesh M, Mohammadi A, Atyabi F, Nabavi SM, Ebrahimi SM, Shahmoradi E, et al. Specific targeting delivery to MUC1 overexpressing tumors by albumin-chitosan nanoparticles conjugated to DNA aptamer. Int J Pharm. 2016;515(1–2):607–15.CrossRefGoogle Scholar
  9. 9.
    McCourt PA, Smedsrød BH, Melkko J, Johansson S. Characterization of a hyaluronan receptor on rat sinusoidal liver endothelial cells and its functional relationship to scavenger receptors. Hepatology. 1999;30(5):1276–86.CrossRefGoogle Scholar
  10. 10.
    Tamura Y, Adachi H, Osuga J-i, Ohashi K, Yahagi N, Sekiya M, et al. FEEL-1 and FEEL-2 are endocytic receptors for advanced glycation end products. J Biol Chem. 2003;278(15):12613–7.CrossRefGoogle Scholar
  11. 11.
    Park S-Y, Jung M-Y, Kim I-S. Stabilin-2 mediates homophilic cell–cell interactions via its FAS1 domains. FEBS Lett. 2009;583(8):1375–80.CrossRefGoogle Scholar
  12. 12.
    Zhou B, Weigel JA, Fauss L, Weigel PH. Identification of the hyaluronan receptor for endocytosis (HARE). J Biol Chem. 2000;275(48):37733–41.CrossRefGoogle Scholar
  13. 13.
    Park S, Jung M, Kim H, Lee S, Kim S, Lee B, et al. Rapid cell corpse clearance by stabilin-2, a membrane phosphatidylserine receptor. Cell Death Differ. 2008;15(1):192–201.CrossRefGoogle Scholar
  14. 14.
    Luo G, Yu X, Jin C, Yang F, Fu D, Long J, et al. LyP-1-conjugated nanoparticles for targeting drug delivery to lymphatic metastatic tumors. Int J Pharm. 2010;385(1):150–6.CrossRefGoogle Scholar
  15. 15.
    Maghari S, Ramezanpour S, Balalaie S, Darvish F, Rominger F, Bijanzadeh HR. Synthesis of functionalized Pseudopeptides through five-component sequential Ugi/Nucleophilic reaction of N-substituted 2-Alkynamides with Hydrazides. J Org Chem. 2013;78(13):6450–6.CrossRefGoogle Scholar
  16. 16.
    Martínez-Jothar L, Doulkeridou S, Schiffelers RM, Torano JS, Oliveira S, van Nostrum CF, et al. Insights into maleimide-thiol conjugation chemistry: conditions for efficient surface functionalization of nanoparticles for receptor targeting. J Control Release. 2018;282:101–9.CrossRefGoogle Scholar
  17. 17.
    Goldburg W. Dynamic light scattering. Am J Phys. 1999;67(12):1152–60.CrossRefGoogle Scholar
  18. 18.
    Mohanraj V, Chen Y. Review on nanoparticles. Trop J Pharm Res. 2006;5:561–73.Google Scholar
  19. 19.
    Esfandyari-Manesh M, Darvishi B, Ishkuh FA, Shahmoradi E, Mohammadi A, Javanbakht M, et al. Paclitaxel molecularly imprinted polymer-PEG-folate nanoparticles for targeting anticancer delivery: characterization and cellular cytotoxicity. Mater Sci Eng C. 2016;62:626–33.CrossRefGoogle Scholar
  20. 20.
    Calvo P, Gouritin B, Chacun H, Desmaële D, D'Angelo J, Noel J-P, et al. Long-circulating PEGylated polycyanoacrylate nanoparticles as new drug carrier for brain delivery. Pharm Res. 2001;18(8):1157–66.CrossRefGoogle Scholar
  21. 21.
    Esfandyari-Manesh M, Mostafavi SH, Majidi RF, Koopaei MN, Ravari NS, Amini M, et al. Improved anticancer delivery of paclitaxel by albumin surface modification of PLGA nanoparticles. Daru. 2015;23(1):1.CrossRefGoogle Scholar
  22. 22.
    Esfandyari-Manesh M, Ghaedi Z, Asemi M, Khanavi M, Manayi A, Jamalifar H, et al. Study of antimicrobial activity of anethole and carvone loaded PLGA nanoparticles. J Pharm Res. 2013;7(4):290–5.Google Scholar
  23. 23.
    Ghasemi Z, Dinarvand R, Mottaghitalab F, Esfandyari-Manesh M, Sayari E, Atyabi F. Aptamer decorated hyaluronan/chitosan nanoparticles for targeted delivery of 5-fluorouracil to MUC1 overexpressing adenocarcinomas. Carbohydr Polym. 2015;121:190–8.CrossRefGoogle Scholar
  24. 24.
    Malek SJ, Khoshchehreh R, Goodarzi N, Khoshayand MR, Amini M, Atyabi F, et al. Cis-Dichlorodiamminoplatinum (II) glyconanoparticles by drug-induced ionic gelation technique targeted to prostate cancer: preparation, optimization and in vitro characterization. Colloids Surf B: Biointerfaces. 2014;122:350–8.CrossRefGoogle Scholar
  25. 25.
    Xu Y, Kim CS, Saylor DM, Koo D. Polymer degradation and drug delivery in PLGA-based drug–polymer applications: a review of experiments and theories. J Biomed Mater Res B Appl Biomater. 2017;105(6):1692–716.CrossRefGoogle Scholar
  26. 26.
    Marslin G, Revina AM, Khandelwal VKM, Balakumar K, Prakash J, Franklin G, et al. Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity. Int J Nanomedicine. 2015;10:3163.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Nanotechnology Research Center, Faculty of PharmacyTehran University of Medical SciencesTehranIran
  2. 2.Department of Pharmaceutics, Faculty of PharmacyTehran University of Medical SciencesTehranIran
  3. 3.Department of Clinical Pharmacy, Tehran Heart CenterTehran University of Medical SciencesTehranIran
  4. 4.Department of Chemistry, Sari BranchIslamic Azad UniversitySariIran

Personalised recommendations