Structural optimization of diblock polymers that undergo thermo-responsive nanoparticle self-assembly for intravitreal drug delivery

0585472 - ÚMCH 2025 RIV GB eng J - Článek v odborném periodiku
Fergie, K. J. - Wilson, D. R. - Kracíková, Lucie - Androvič, Ladislav - Yamagata, H. - Wang, E. B. - Yoon, H. - Lynn, G. M. - Laga, Richard
Structural optimization of diblock polymers that undergo thermo-responsive nanoparticle self-assembly for intravitreal drug delivery.
European Polymer Journal. Roč. 212, 27 May (2024), č. článku 113054. ISSN 0014-3057. E-ISSN 1873-1945
Grant CEP: GA MŠMT LX22NPO5102; GA MŠMT(CZ) LUAUS24239
Institucionální podpora: RVO:61389013
Klíčová slova: thermoresponsive polymer * polymer micelle * ocular drug delivery
Obor OECD: Polymer science
Impakt faktor: 6, rok: 2022
Způsob publikování: Open access
https://www.sciencedirect.com/science/article/pii/S001430572400315X?via%3Dihub

Certain diseases of the eye require frequent intravitreal injections to sustain active drug concentrations due to the limited volume (≤50 µL) of solution that can be administered each injection. Drug delivery systems have been evaluated to reduce dosing frequency but achieving (i) high concentrations with low viscosity (<100 cP) and (ii) narrow range of particle size (∼20–70 nm) to prolong drug activity without affecting vision remain major challenges. To address these challenges, we synthesized a combinatorial library of thermo-responsive polymer-drug conjugates with diblock architecture and assessed how various parameters (monomer unit composition, block length, drug density and attachment site) affect properties impacting ocular injection suitability. Our screens identified a lead composition, p[(N-isopropylmethacyrlamide)–co-(N-benzylmethacrylamide)]-b-p(N-(2-hydroxypropyl)methacrylamide) with 20 mol% N-benzylmethacrylamide (p[(NIPMAM)–co-(BnMAM)]-b-p(HPMA)), that exists as unimers at room temperature that can be highly concentrated (200 mg/mL) and injected at low viscosity but self-assemble into 20–70 nm particles upon injection into vitreous humor at body temperature. Furthermore, covalent attachment of representative small molecule, peptide- and protein-based drugs had minimal to no impact on thermoresponsive and hydrodynamic behavior highlighting the versatility of the lead composition as a platform for delivering a broad range of different drug molecules.
Trvalý link: https://hdl.handle.net/11104/0353163