Preparation and characterization of biocompatible and thermoresponsive micelles based on poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) grafted on polysuccinimide for drug delivery.
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.
Department of Biomedical Engineering, Chung Yuan Christian University, Chung Li, Taiwan Stroke Center and Department of Neurology, Chang Gung Memorial Hospital, Linkou Medical Center and College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Jih-Chao
JC
Yeh
Department of Biomedical Engineering, Chung Yuan Christian University, Chung Li, Taiwan.
Ya-Ting
YT
Hsu
Department of Biomedical Engineering, Chung Yuan Christian University, Chung Li, Taiwan.
Chao-Ming
CM
Su
Department of Biomedical Engineering, Chung Yuan Christian University, Chung Li, Taiwan.
Ming-Chen
MC
Wang
Stroke Center and Department of Neurology, Chang Gung Memorial Hospital, Linkou Medical Center and College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Tsong-Hai
TH
Lee
Department of Biomedical Engineering, Chung Yuan Christian University, Chung Li, Taiwan lou@cycu.edu.tw.
Shyh-Liang
SL
Lou
D000180:Acrylic Resins / Q000737:chemistry*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D001672:Biocompatible Materials; D016503:Drug Delivery Systems; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D010455:Peptides / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared
D000180:Acrylic Resins; D001672:Biocompatible Materials; D008823:Micelles; D010455:Peptides; C403811:poly(IPAAm-co-DMAAm); C025252:poly-DL-succinimide; D001224:Aspartic Acid
Temperature-sensitive polymeric micelles; anti-inflammation; cytotoxicity; hemolysis; hesperetin