Preparation and characterization of biocompatible and thermoresponsive micelles based on poly(N-isopropylacrylamide-co-N,N-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.

Cyclodextrin-polyhydrazine degradable gels for hydrophobic drug delivery

“…A CDfunctionalized polyhydrazine (PH) was the second polymer used in this work. This polymer is a derivative of polysuccinimide, which is a biodegradable and non-toxic material [37]. Two sets of in-situ formed hydrogels with different crosslinking densities were prepared by mixing aqueous solutions of DA and PH.…”

Temperature-Responsive Smart Nanocarriers for Delivery Of Therapeutic Agents: Applications and Recent Advances

“…1–9 The most utilized nanocarriers in recent years have been based on NPs including liposomes, dendrimers, polymeric NPs, metal NPs, carbon nanomaterials (e.g., fullerenes, carbon nanotubes (CNTs)), solid lipid NPs (SLNs), nanoshells and magnetic NPs, mesoporous silica NPs (MSNs), as well as novel nanostructures based on albumin, chitosan, etc. 5,10–17 …”

“…50 Moreover, diverse methodologies have been used for characterization of the thermoresponsive polymeric NPs such as cryogenic transmission electron microscopy (cryo-TEM), 51 atomic force microscopy (AFM), 52 nuclear magnetic resonance (NMR) spectroscopy, 53,54 small-angle X-ray scattering (SAXS), 51,55,56 Fourier-transform infrared spectroscopy (FT-IR), 10 UV–vis, 46 and static and/or dynamic light scattering (SLS/DLS). 46,57 …”

Influence of Block versus Random Monomer Distribution on the Cellular Uptake of Hydrophilic Copolymers

“…They are have been widely used for biomedical applications and were previously shown to be non-toxic to cells. [29][30][31][32][33][34] While strictly hydrophobic monomers were avoided here to prevent aggregation, this trio of monomers covers an interesting gradient of hydrophilicity (HEAm > NAM >DMA) which is expected to affect the interaction of the resulting copolymers with both extracellular proteins and the lipid bilayer of cells.…”