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

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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.

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Acknowledgements

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

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Authors and Affiliations

  1. Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Mehdi Esfandyari-Manesh, Fatemeh Atyabi & Rassoul Dinarvand

  2. Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Masoome Abdi, Fatemeh Atyabi & Rassoul Dinarvand

  3. Department of Clinical Pharmacy, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran

    Azita Hajhossein Talasaz

  4. Department of Chemistry, Sari Branch, Islamic Azad University, Sari, Iran

    Seyedeh Masoumeh Ebrahimi

Authors
  1. Mehdi Esfandyari-Manesh
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  2. Masoome Abdi
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  3. Azita Hajhossein Talasaz
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  4. Seyedeh Masoumeh Ebrahimi
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Correspondence to Rassoul Dinarvand.

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Esfandyari-Manesh, M., Abdi, M., Talasaz, A.H. et al. S2P peptide-conjugated PLGA-Maleimide-PEG nanoparticles containing Imatinib for targeting drug delivery to atherosclerotic plaques. DARU J Pharm Sci 28, 131–138 (2020). https://doi.org/10.1007/s40199-019-00324-w

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  • DOI: https://doi.org/10.1007/s40199-019-00324-w

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