Amino acid-equipped poly(ester amide) nanoparticles for improved encapsulation efficiency of lipophilic...

The efficient delivery of lipophilic drugs still remains a major challenge in pharmaceutical nanotechnology, particularly due to limitations in drug loading, drug stability, and the biocompatibility of polymeric nanocarriers. Poly(ester amide)s represent a promising class of biodegradable materials and were investigated in the present study for the delivery of the anti-inflammatory, lipophilic drug 6-bromoindirubin-3'-glycerol-oxime ether (6BIGOE). Poly(ester amide)s incorporating the aromatic and non-aromatic α-amino acids l-phenylalanine or l-valine, next to glycolic acid as ester component, were synthesized by ring-opening polymerization and used to prepare nanoparticles via nanoemulsification in comparison to the widely used poly(lactic-co-glycolic acid) (PLGA). All polymers formed monodisperse nanoparticles of around 200 nm with anionic surfaces (ca. -20 mV) and comparable drug release profiles. Advantageously, the encapsulation efficiency of 6BIGOE was significantly improved to 63-78 % using poly(ester amide)s compared to 42 % for PLGA, confirmed by molecular dynamic simulations revealing enhanced interactions and miscibility between poly(ester amide)s and 6BIGOE. Poly(ester amide) nanoparticles showed higher glass transition temperatures compared to PLGA, indicating an improved thermo-mechanical stability. In human monocytes, 6BIGOE-loaded poly(ester amide) nanoparticles demonstrated excellent biocompatibility with pronounced anti-inflammatory activity by modulating pro- and anti-inflammatory mediators which highlights their potential as a versatile and tunable platform for the delivery of lipophilic anti-inflammatory drugs.