Glucan polymer, polymer micelle and medicine carrier system
A polymer glue and carrier system technology, applied in the field of polymer micelles and drug carrier systems, dextran polymers, can solve the problems of poor targeting, insufficient stability, limited application of polymer micelles, etc., to reduce damage , Good hydrogen peroxide responsiveness, good responsiveness
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Embodiment 1
[0059] A kind of preparation method of dextran polymer and micelle with hydrogen peroxide responsiveness, its synthetic route is such as figure 1 shown, the specific steps are as follows:
[0060] 1) First carry out the reaction of boron ester and dodecanoic acid, under nitrogen protection, put boron ester raw material A (1 eq) and dodecanoic acid (1.5 eq) into a 25 mL round bottom flask and dissolve with DCM. DMAP (0.2 eq) EDCI (1.5 eq) and Et3N (0.5 eq) were respectively dissolved in DCM and injected into the system using a syringe. The reaction solution was reacted at room temperature for 18h, followed by TLC spot plate. After the reaction was completed, water was added to quench. The aqueous layer was extracted 4 times with DCM, the organic phases were combined and MgSO was used 4 Dry, filter with suction, spin dry to obtain the crude product, and then purify it by column chromatography. The product was a yellow oil. reaction process such as figure 2 shown.
[0061...
Embodiment 2
[0066] The critical micelle concentration (CMC) of the micelles described in Example 1 was measured using fluorescent probe technology, and the specific steps were as follows:
[0067] 1) Preparation of fluorescent probe pyrene in methanol solution
[0068] Dissolve 0.0051 g of pyrene in 25 ml of methanol to obtain a pyrene solution with a concentration of 1.01×10-3 mol / L, and then dilute with methanol to obtain a pyrene solution of 1.616×10-6 mol / L.
[0069] 2) Preparation of DA-B-DEX aqueous solutions of different concentrations
[0070] The preparation concentration is 1 × 10 -4 , 1×10 -3 , 1×10 -2 , 1×10 -1 , 1, 10, 100, 1000 mg / ml of DA-B-DEX solution.
[0071] 3) Preparation of pyrene-containing micelles
[0072] Take 150 μl of the prepared pyrene solution, put it into several 10 ml volumetric flasks, and evaporate the methanol to dryness. Then, 10 ml of each concentration of DA-B-DEX solution was added to a 10 ml volumetric flask containing a trace amount of pyre...
Embodiment 3
[0076] A method for preparing a polymer micelle drug carrier with hydrogen peroxide response, the steps are as follows:
[0077] 1) Dissolve DA-B-DEX (100 mg) in DMSO (10 ml), add dropwise to PBS buffer (100 ml, pH 7.4) under stirring, and keep stirring for 30 min. Spontaneous formation of micelles was confirmed by observation of a clear opalescent solution.
[0078] 2) At the same time, prepare DA-B-DEX micelles that physically encapsulate doxorubicin. DA-B-DEX (91.5 mg) and DOX (8.5 mg) are dissolved in 10 mL of dimethyl sulfoxide (DMSO) together under stirring. It was added dropwise to 100 mL of PBS buffer and stirred for 30 min. Dialysis was carried out through a dialysis bag (molecular weight cut-off = 3.5KD) for 24 hours to remove organic solvents and free drugs, and finally freeze-dried for storage.
[0079] 3) The particle size distribution was measured using a Malvern laser particle sizer (Zetasized Nano, ZS, Malvern, United Kingdom). The morphology and size of mic...
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