Method for preparing intelligent target medicine carrying composite micelles
A composite micelle, targeting technology, applied in pharmaceutical formulations, medical preparations with inactive ingredients, and medical preparations containing active ingredients, etc., can solve the problems of poor polymer reversibility and slow response speed. Long-term blood circulation, simple and accurate operation, and the effect of improving the sensitivity of phase transition
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Embodiment 1
[0040] A preparation method of intelligent targeted drug-loaded composite micelles, the intelligent targeted drug-loaded composite micelles use temperature-sensitive polymers to control the "shielding" and "unshielding" states of targeting ligands on the surface of nanoparticles, that is, the The targeting ligands on the surface of nanoparticles are in a "shielding" state during normal blood circulation, and when the tumor site is locally heated to 40-44°C, the targeting ligands on the surface of nanoparticles are in a "unshielding" state, thereby restoring The targeting ability of nanoparticles, the preparation method comprises the following steps:
[0041] (1) Synthesis of thermosensitive block copolymers, non-targeting amphiphilic block copolymers and targeting amphiphilic block copolymers
[0042] 1) Synthesis of non-targeting amphiphilic block copolymer polyethylene glycol-polyε-caprolactone (mPEG-b-PCL) by ring-opening polymerization (ROP)
[0043] Add 1 g of polyethylene...
Embodiment 2
[0070] A method for preparing a temperature-sensitive targeting composite micelle that can be used in an in vivo temperature environment, the operation of preparing the composite micelle and the ELISA characterization are basically the same as in Example 1, except that the temperature-sensitive block copolymer used is Poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide)-b-polyε-caprolactone (P(NIPAAm-co-DMAAm)-b-PCL), its subcritical solution The temperature is adjusted to between 39-40°C, and the preparation route is as follows
[0071] 1) Common free radical synthetic macromolecular initiator poly(N-isopropylacrylamide-N,N-dimethylacrylamide) P(NIPAAm-co-DMAAm)-OH
[0072] 0.230 mmol of chain transfer agent mercaptoethanol, 0.08 mmol of initiator azobisisobutylcyanide (AIBN), 2.3 mmol of monomer N-isopropylacrylamide (NIPAAm) and N,N-dimethylacrylamide (DMAAm) Put 1 mmol in a 25 mL single-necked round bottom flask, then add 2 mL of anhydrous N,N-dimethylformamide (DMF) for...
Embodiment 3
[0077] A method for preparing targeted composite micelles that are sensitive to both temperature and pH. The operation of preparing composite micelles such as ELISA characterization and other operations is basically the same as in Example 1, except that the temperature-sensitive block copolymer used is polymer (N-isopropylacrylamide-co-acrylamide-co-acrylic acid)-b-polyε-caprolactone (P(NIPAAm-co-AAm-co-AA)-b-PCL), its low critical temperature At the same time, it is regulated by pH and temperature. Considering the complex environment of the human body, using a variety of environmental stimuli to regulate the phase transition of the polymer will allow more precise regulation and thus have better clinical application prospects.
[0078] The preparation route of the pH / temperature synergy-sensitive block copolymer is shown below.
[0079] 1) Ordinary free radical synthetic macromolecular initiator poly(N-isopropylacrylamide-co-acrylamide-co-acrylic acid) P(NIPAAm-co-AAm-...
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