Smart nanoparticles based on pullulan-g-poly(N-isopropylacrylamide) for controlled delivery of indomethacin

Double hydrophilic thermo-responsive pullulan-g-poly(N-isopropylacrylamide) (P-g-pNIPAM) copolymers with two different molecular weight of thermosensitive grafts were synthesized and used for preparation of indomethacin-loaded nanoparticles by dialysis and nanoprecipitation method. The polymers form aggregates in aqueous solution at a concentration of 10g/L, above their critical aggregation concentration (3.36g/L) and below the lower critical solution temperature (LCST). After indomethacin loading, nanoparticles with compact and uniform structure were formed below the LCST. The effects of copolymer composition, concentration, and the feed polymer/drug ratio on the particle size, drug loading content (DLC) and entrapment efficiency (EE) were investigated. DLC increased with drug feeding, reaching a maximum value of 40% at the ratios of 1/1. Smaller particles (145nm) with narrower size distribution were obtained from polymer with a higher molecular weight of pNIPAM grafts. FT-IR and ¹H NMR spectra proved that the main driven force for the aggregation was the hydrogen bonding between indomethacin and the pNIPAM side chains of copolymer. The indomethacin release rate from nanoparticles was influenced by temperature, because of the dissociation of the hydrogen bonds at high temperatures, the degree of drug loading, and the pH of the release media.