PEtOxylated polyesteramide nanoparticles for the delivery of anti-inflammatory drugs

Poly(ester amide)s (PEAs) consisting of l-valine (Val), glycolic acid (G), and l-isoleucine (Ile), i.e., PValG and PIleG, and various poly(2-ethyl-2-oxazoline)-block-poly(ester amide) copolymers (PEtOx-b-PEA) were investigated for their suitability as particle-based delivery systems for the anti-inflammatory drugs BRP-187 and BRP-201. A small-scale, high-throughput formulation approach was utilized to evaluate the nanoparticle properties in dependence of the composition of mixtures of PEA homo- and copolymers. Atomistic molecular dynamics simulations of PValG and PIleG with the active ingredients indicated thermodynamic compatibility of the PEAs with the drugs. Drug encapsulation studies confirmed the formation of stable formulations, and the enzymatic degradation of the nanoparticles was also demonstrated. The nanoparticles exhibited no cytotoxicity and were able to efficiently deliver the active pharmaceutical ingredients, i.e., BRP-187 and BRP-201 into macrophages and HEK293 cells. All nanoparticle systems displayed anti-inflammatory effectiveness as they were able to suppress cellular 5-lipoxygenase activity. The most promising effects were obtained with the block copolymer-based PEtOx-b-PEA nanoparticles, which revealed an enhanced performance compared to the control PLGA nanoparticles.