Synthesis of poly(alpha,beta-[N-(2-hydroxyethyl)-L-aspartamide])-folate for drug delivery

Poly(alpha,beta-[N-(2-hydroxyethyl)-L-aspartamide])-folate (PHEA-FA) was synthesized by linking FA to a poly(alpha,beta-[N-(2-hydroxyethyl)-L-aspartamide]) (PHEA) backbone. The chemical structure of PHEA-FA was characterized by (1)H-NMR and FT-IR. The molecular weights of the polymers were determined by combined size-exclusion chromatography and multiangle laser light scattering (SEC-MALLS) analysis. Due to the incorporation of FA, PHEA-FA exhibited pH-sensitive aggregation behavior in aqueous media. As characterized by UV-Vis spectroscopy and fluorescence spectroscopy, PHEA-FA could self-assemble to form aggregates in acidic and neutral aqueous solutions, and became soluble in a basic solution. The potential application of PHEA-FA in drug delivery was explored. Drug-loaded PHEA-FA nanoparticles were fabricated and the in vitro drug release of the drug-loaded nanoparticles was investigated. Transmission electron microscopy (TEM) showed that the nanoparticles exhibited a spherical morphology with particle sizes <100 nm. The in vitro study showed PHEA-FA exhibited enhanced cell uptake on the folate-receptor-positive cells because of the folate-mediated targeting.