Preparation And Application Of Magnetic Thermosensitive Hydrogel

To achieve the pulsatile release, decrease the harmful side-effects and enhance the therapy efficacy of anti-cancer drugs, the magnetic thermosensitive hydrogel formed with amphiphilic poly(D,L-lactide -co-glycolide)-b-poly(ethylene glycol)-b-poly(D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) which contained magnetic nanoparticles was prepared. When the magnetic thermosensitive hydrogel were injected into body, we can control the temperature of the system by a high frequency alternating magnetic field (AMF).Therefore, we can trigger the on-demand pulsatile drug release from the magnetic thermosensitive hydrogel. This project investigated the heating ability of magnetic thermosensitive hydrogel in alternating magnetic field(AMF) in vitro. In addition, the release of troxerutin from magnetic thermosensitive hydrogel under different temperatures in vitro was also researched. The project mainly includes as follows:1 Synthesis and characterization of thermosensitive hydrogelThe triblock copolymers PLGA-PEG-PLGA were synthesized by ring-opening polymerization of D, L-lactide and glycolide with polyethy–lene glycol(PEG)in the presence of stannous octoate. Chemical constitution of copolymer was determined by infrared spectra and 1H-NMR respectively;the gel permeation chromatography(GPC) was used to obtain the molecular weight; a single test-tube inverting method was employed to determine the phase transition temperature; dynamic rheological measurements were employed to quantify the viscoelastic properties during the physical gelation; the micelles of the copolymer were detected according to Dynamic light scattering(DLS); the Zeta potential of micelles was determined; the morphology of micelles was analyzed by using transmission electron microscopy(TEM).The results indicated that the final product is PLGA-PEG-PLGA.The final product is pure and stable.The molecular weight distribution of the copolymers is uniform. The aqueous solution of the copolymers possessed good thermo-sensitivity in a certain concentration range.The phase transition temperature of the copolymers can be adjusted by changing the proportion of materials and the molecular weight of PEG. In addition, the results of rheology analysis also showed that the hydrogel possessed good thermosensitivity. The size and its distribution of polymer micelles (LA:GA:PEG1500=6:1:3) were observed by transmission electron micro -scope(TEM) and dynamic light scattering(DLS) to be uniform, mainly about 35 nm. The Zeta potential of micelles is about -6.15 mV.2 The heating effect of magnetic thermosensitive hydrogelThe effect of magnetic fluid on the thermosensitivity of the thermosensitive hydrogel was observed. Different concentrations of magnetic thermosensitive hydrogel were prepared and different currents were used.The influences of the concentration of magnetic fluid and current of magnetic field on the heat effect were separately observed.The results showed that the magnetic thermosensitive hydrogel retains the thermosensitivity of original hydrogel.The heating ability of the magnetic thermosensitive hydrogel is positively correlated with the concentration and the current of alternating magnetic field(The related coefficients are all higher than 0.97).3 The release in vitro of troxerutinThe effect of troxerutin on the thermosensitivity of the thermosensitive hydrogel was observed. The thermosensitive hydrogel in which loaded troxerutin was prepared by physical blending using the PLGA-PEG-PLGA whose phase transition temperature is 25℃as the carrier, and then this paper put an emphasis on the release of troxerutin from magnetic thermosensitive hydrogel under different temperatures (40 ℃and 30℃) in vitro using a membraneless model. The results showed that troxerutin had little influence on thermosensitivity of the hydrogel. Our results proved that we could change the drug release rate by changing the temperatures of PLGA-PEG-PLGA.In summary, the magnetic thermosensitive hydrogel made from PLGA-PEG-PLGA could be the carriers for anticancer drug. We can control the drug release rate by changing the temperatures of PLGA-PEG-PLGA with alternating magnetic field.