Study Of Stimuli-responsive Nanogels For Drug Delivery

Nanogels have shown many interesting intrinsic properties, such as soft nature, biocompatibility, nanometer size, These properties, together with nanogels ability to incorporate active pharmaceutical ingredients, peptides, open many opportunities for their biomedical utilization:(1) Nanogels can effectively prevent the load protein drugs agglutinate denatured;(2) Nanogels can be sustained release drug for a long time;(3) Nanogels easy to use, the general method is injected or oral medicine;(4) Nanogels can effectively prevent the leak of drugs, improve drug efficacy and reduce side effects. However, Nanogels have shortcomings in intelligent drug delivery. Stimuli-responsive nanogels with the ability to respond to typical biological stimuli(such as small changes in temperature, p H, or the presence of certain biomolecules) or to external triggers(such as light irradiation or the presence of magnetic fields), Which can makes the drug regularly release in a particular place. Compared with the traditional responsive hydrogel, stimuli-responsive nanogels are more sensitive to the change of environment, with a higher efficiency of drug release. This paper in view of reducing glutathione high expression in tumor cells and high blood glucose levels of diabetes, redox-responsive nanogel and glucose-sensitive nanogel are prepared.Ⅰ.The study of redox-responsive nanogel is used as drug carrierRedox-responsive nanogel was prepared from methacrylic acid, N,N-bis(acryloyl)cystamine crosslinker, 2,2-Azobisisobutyronitrile as initiator via precipitation polymerization. Doxorubicin, as a model anticancer drug, was loaded into the redox-responsive nanogel. The characterization of redox-responsive nanogel were studied by scanning electron microscope(SEM), fourier transform infrared spectrometer(FT-IR) measurements; Ultraviolet–visible spectroscopy(UV-VIS) was used to study the redox-responsive of nanogel; DOX-loaded nanogels exhibit faster release behavior in reductive solution,and the cumulative release rate of DOX increased along with the crosslinker(BACy) increasing. The cytotoxicity of nanogels without DOX against NIH-3T3 and MCF-7 cells was measured by CCK-8 assay, nanogel without DOX exhibited no cytotoxicity. The antitumor activities of DOX-loaded nanogels almost equivalent to free DOX under otherwise the same conditions. The results of blood compatibility evaluation show that the blood compatibility of PMAA-300 nm is superior to the PMAA-600 nm under the same concentration.Ⅱ.The study of glucose-sensitive nanogel is used as drug carrierGlucose-sensitive nanogel was prepared from methacrylic acid,3-Acrylamidophenylboronic acid, 2,2-Azobisisobutyronitrile as initiator, ethyleneglycol dimethacrylate as crosslinker via precipitation polymerization. Insulin was loaded into the glucose-sensitive nanogel. The characterization of glucose-sensitive nanogel were studied by scanning electron microscope(SEM), fourier transform infrared spectrometer(FT-IR) measurements. Dynamic light scattering was used to study the glucose-sensitive of nanogel. In vitro release experiments show that the cumulative release rate of insulin increased along with the glucose of PBS increasing. The results of CCK-8 assay proved that nanogel without insulin exhibited no cytotoxicity against NIH-3T3. The results of blood compatibility evaluation show that glucose-sensitive nanogel has good blood compatibility when the concentration is less than 10 mg/m L. At the same time through animal experiments verify that glucose-sensitive nanogel can quickly response to glucose and release insulin, compared with no sensitivity of nanogel, it can maintain a stable and mild blood glucose concentration range. Histological analysis proved that when the injected dose of glucose nanogel is 500 mg/kg, the rat has no acute toxic reaction.