Copolymer with temperature/PH dual-sensibility and preparation and application thereof
A dual-sensitive, copolymer technology, applied in the preparation of temperature-sensitive/pH double-sensitive gel drug delivery system and pH-sensitive micellar drug delivery system, temperature/pH double-sensitive copolymer field, can solve drug leakage, Inability to deliver drugs, insensitive response to pH changes, etc., to achieve the effect of increasing stability
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Embodiment 1
[0037] Example 1: Synthesis of temperature / pH double-sensitive OLH-b-PLGA-b-PEG-b-PLGA-b-OLH
[0038] (1) Synthesis of temperature-sensitive PLGA-b-PEG-b-PLGA block copolymers
[0039] Take polyethylene glycol (PEG1000 or PEG1500) and lactide (LA), glycolide (GA) and catalyst stannous octanoate (Sn (Oct) 2), wherein the mass ratio of PEG to LA and GA mass sum 2:5, the molar ratio of LA to GA is 5:1, Sn(Oct)2 is 0.5% of the mass sum of all monomers, put it into a dry polymerization tube, and after deoxygenation by nitrogen, seal the tube under vacuum, Reacted at 150°C for 8h to obtain a colorless and transparent semi-solid product. The resulting crude product is dissolved in cold water (less than 10°C), heated to 80°C to precipitate the copolymer, and the low molecular weight water-soluble copolymer and unreacted monomer compounds are removed. After three repetitions, the isolated copolymer is decompressed at room temperature Dry to obtain purified PLGA-PEG-PLGA terpolymer wi...
Embodiment 2
[0063] Embodiment 2: Phase transition temperature (PIT) is measured
[0064]Weigh two proportions of appropriate copolymers, dissolve them in pH7.4 PBS solution, prepare a copolymer solution with a concentration of 20%, transfer the solution to a glass container, adjust the magnetic stirring speed to 200rpm, and keep the water bath slowly warming up , the heating rate was 1°C / min, and the temperature at which the clear solution formed a gel was recorded. The phase transition temperature of the copolymer used for injection of sustained-release materials is 36°C, and the phase transition pH is 7.0-7.4, which ensures that it exists in a gel state in a physiological environment and can release drugs slowly. The phase transition temperature of the material used in the micellar targeted drug delivery system is 59°C, which ensures that it exists in a solution state in a physiological environment and can be used for intravenous injection.
Embodiment 3
[0065] Embodiment 3: Preparation of OLH-PLGA-PEG-PLGA-OLH blank micelles
[0066] Take 10mg of OLH-PLGA-PEG-PLGA-OLH into a small vial, add 20ml of deionized water, and stir magnetically for 5 hours to prepare blank micelles. The micelles have light blue opalescence, and the particle size is about 90nm. The distribution is narrow.
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