Preparation and characterization of biocompatible and thermoresponsive micelles based on poly( <i>N</i> -isopropylacrylamide- <i>co-N</i> , <i>N</i> -dimethylacrylamide) grafted on polysuccinimide for drug delivery

Abstract

Biocompatible and temperature-sensitive amphiphilic polymeric micelles comprised of poly(succinimide)-g-poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (PSI-g-poly(NIPAAm-co-DMAAm)) were synthesized to use as new drug carriers. The PSI-co-poly(PNIPAAm-co-DMAAm) polymers were prepared by nucleophilic opening of poly(succinimide) using amino-terminated poly(NIPAAm-co-DMAAm). The lower critical solution temperature of the copolymer was 40.6℃ higher than normal human body temperature. The blank polymeric micelles were observed to have a regular spherical shape, and the particle sizes were approximately 85 nm. This copolymer exhibited no significant cytotoxicity and hemolysis indicated that the micelles had good biocompatibility. In addition, these polymeric micelles encapsulated the anti-inflammatory drug, hesperetin, in the inner core with a drug loading content of approximately 20%. The release profiles of hesperetin showed a significant temperature-sensitive switching behavior. The hesperetin release response was dramatically lower at a temperature below the lower critical solution temperature as compared with a temperature above the lower critical solution temperature. The lipopolysaccharide-induced nitric oxide production inhibition experiments demonstrated that hesperetin-encapsulated micelles showed a significant reduction. In this study, the biocompatible temperature-sensitive micelles based on PSI-g-poly(NIPAAm-co-DMAAm) have great potential to act as a suitable carrier for drug delivery.