A kind of boric acid ester functionalized pluronic polymer, preparation method and application in the preparation of drug delivery system
A delivery system and a technology for preparing drugs, which are applied in the direction of drug combinations, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., can solve problems such as toxic side effects, strong hydrophilicity, and unstable carriers, and achieve The effect of improving stability
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Embodiment 1
[0053] Preparation of boronate functionalized Pluronic polymers:
[0054] The synthetic route of boronate functionalized Pluronic polymers is shown below:
[0055]
[0056] The preparation method of boronate functionalized Pluronic polymer comprises the following steps:
[0057] S1. Preparation of carboxyl-modified pluronic represented by formula I-2:
[0058] Pluronic P123 (10 g, 1.7 mmol, ), adipic anhydride (0.7 g, 5.5 mmol), and anhydrous triethylamine (0.55 g, 5.4 mmol), as shown in formula I-1, were added to a 100 mL circular In the bottom reaction flask, 20 mL of dichloromethane was added as a solvent. The reaction was carried out for 12 h, the dichloromethane was removed by rotary evaporation, the product was dissolved in ethanol, and dialyzed with a dialysis bag with a molecular weight cut-off of 3500 Da. Freeze-drying to obtain 8.7 g of the carboxyl-modified Pluronic product shown in formula I-2, with a yield of 85.04%;
[0059] S2. Preparation of boronate funct...
Embodiment 2
[0063] Preparation of micelles and their particle size and morphology:
[0064] 1. Preparation of Pluronic P123 blank micelles:
[0065] Weigh 30 mg of Pluronic P123 shown in formula I-1 into a 25 mL eggplant-shaped bottle, add 1 mL of dichloromethane, rotate at 50 °C for 30 min, and then put it in a 60 °C oven to dry overnight; then put the round bottom bottle into a 50 Hydrate and heat in a ℃ water bath for 15 min, add 10 mL of deionized water (pH 7.4) at 50 ℃ to the bottle, quickly stir and vortex, and filter the solution with a 0.22 μm filter to obtain a milky white or transparent micellar emulsion, which is Pulan Nick P123 blank micelles.
[0066] Take 1 mL of micellar emulsion for particle size detection using a nanoparticle size analyzer (DLS), and use a transmission electron microscope for morphology detection. The results are as follows Figure 3a and Figure 3b .
[0067] Depend on Figure 3a and Figure 3b It can be seen that the particle size of Pluronic P123...
Embodiment 3
[0073] Encapsulation efficiency, drug loading efficiency and particle size of drug-loaded micelle particles:
[0074] 1. Preparation of Pluronic P123 drug-loaded micelles:
[0075] Weigh 30 mg of Pluronic P123 and doxorubicin to co-dissolve in 1 mL of anhydrous dichloromethane, steam at 50 °C for 30 min, and then put it in a 60 °C oven to dry overnight; then put the round-bottom bottle into a 50 °C water bath. Heat for 15 min, add 10 mL of deionized water (pH 7.4) at 50°C to the bottle, stir and vortex quickly, filter the solution with a 0.22 μm filter to obtain a red emulsion or a transparent solution, which is Pluronic P123 drug-loaded gel bundle.
[0076] 2. Preparation of boronate functionalized Pluronic polymer drug-loaded micelles:
[0077] Weigh 30 mg of boronate-functionalized pluronic polymer and doxorubicin to dissolve in 1 mL of anhydrous dichloromethane, steam at 50 °C for 30 min, and then put it in a 60 °C oven to dry overnight; Put it into a 50°C water bath fo...
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