Polyelectrolyte nanoparticles based on poly[N-(2-hydroxypropyl)methacrylamide-block-poly(N-(3-aminopropyl)methacrylamide] copolymers for delivery of heparin-binding proteins

0570910 - ÚMCH 2024 RIV GB eng J - Journal Article
García-Briones, Gabriela S. - Laga, Richard - Černochová, Zulfiya - Arjona-Ruiz, Carely - Janoušková, Olga - Šlouf, Miroslav - Pop-Georgievski, Ognen - Kubies, Dana
Polyelectrolyte nanoparticles based on poly[N-(2-hydroxypropyl)methacrylamide-block-poly(N-(3-aminopropyl)methacrylamide] copolymers for delivery of heparin-binding proteins.
European Polymer Journal. Roč. 191, 13 June (2023), č. článku 111976. ISSN 0014-3057. E-ISSN 1873-1945
R&D Projects: GA ČR(CZ) GA23-06746S; GA ČR(CZ) GA22-02836S; GA MŠMT(CZ) LTAUSA18173; GA MŠMT LX22NPO5102
Institutional support: RVO:61389013
Keywords : polyelectrolyte nanoparticles * APMA * heparin
OECD category: Polymer science
Impact factor: 6, year: 2022
Method of publishing: Limited access
https://www.sciencedirect.com/science/article/pii/S0014305723001593?via%3Dihub

In addition to the delivery of therapeutic nucleic acids and low-molecular weight drugs, polyelectrolyte nanoparticles (NPs) have recently been studied as carriers for protein delivery. However, the stability of NPs during isolation steps, which ensures their easy redispersion, needs to be solved empirically for individual systems using cryoprotectants and stabilizers. To avoid the use of additives, we studied the formation of polyelectrolyte NPs consisting of a newly synthesized polycationic diblock copolymer based on poly(N-(2-hydroxypropyl)methacrylamide)-block-poly(N-(3-aminopropyl)methacrylamide) (p(HPMA-b-APMA) and heparin (Hep). The p(APMA) blocks electrostatically complexed with Hep, and the p(HPMA) blocks formed a neutral corona of NPs, limiting NP aggregation. Self-assembly was monitored through the changes in size and zeta potential of the formed NPs, which depended on the copolymer composition and the concentration of polyelectrolyte solutions. The interactions between the NP components were analysed by FTIR spectroscopy, and XPS analysis indicated the presence of p(HPMA) blocks on the surface of the NPs. The encapsulation of the model chemokine CXCL12 and basic fibroblast growth factor (FGF-2) was driven by their specific bioaffinity for Hep, resulting in a high 90 % entrapment efficiency and increased protein stability. CXCL12 was released over 48 h, while FGF-2 exhibited a sustained release of up to 38 % over four weeks. In addition, the released CXCL12 effectively stimulated the migration of macrophages and T-lymphocyte cells, indicating the preserved protein bioactivity. Considering the proven noncytotoxic performance of the NPs towards fibroblasts and mesenchymal stem cells, the polyelectrolyte NPs of p(HPMA-b-APMA) and Hep loaded with heparin-binding proteins can be considered as promising candidates for the controlled delivery of bioactive proteins in biomedical applications.
Permanent Link: https://hdl.handle.net/11104/0342283