Tumor targeting nanometer micelle, preparation method and application of tumor targeting nanometer micelle as drug carrier
A nanomicelle, tumor targeting technology, applied in the field of biomedicine, can solve the problems of chemoresistant cancer cell clone and distant metastasis, chemotherapy can not achieve therapeutic effect, large side effects, etc., achieves good degradability, suitable for The effect of drug loading and easy operation
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[0079] Example 1 Chondroitin sulfate - synthesis of rivet polymer:
[0080] (1) Synthesis of chondroitin sulfate - diacrylhydrazide sulfate: weigh 0.5g chondroitin sulfate dissolved in 100mL distilled water, stirred to make it fully swelled and dissolved, and then added 3.52g adipic acid dihydrazide, 2.0g 1- (3-dimethylaminopropyl)-3-ethyl carbon diimide hydrochloride and 0.8g N- hydroxysuccinimide at room temperature for 24 hours, dialyzed with distilled water for three days, freeze-dried to obtain the intermediate product chondroitin sulfate - adihydrazide.
[0081] (2) Weigh 30mg of rhubarbic acid dissolved in 10mL dimethyl sulfoxide, to which 5 times the molar amount of 1- (3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, equivalent to 5 times the molar amount of rhubarbic acid N- hydroxysuccinimide, stirred at room temperature for 4 hours to activate rhubarbic acid.
[0082](3) Synthesis of chondroitin sulfate - rhubarbic acid polymer: Weigh the chondroitin sulfate ...
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[0086] Example 2 cross-linked chondroitin sulfate - rivetate - lipoic acid polymer nanomiscle preparation of docetaxel
[0087] (1) 50mg of chondroitin sulfate - rhubarbic acid - lipoic acid (prepared in Example 1), ultrasonically dispersed in 10mL deionized water, standby; also said to take 15mg of docetaxel dissolved in 1mL methanol, under strong stirring case slowly added to the above chondroitin sulfate - rhubarbic acid - lipoic acid polymer aqueous solution, room temperature avoid light after strong stirring for 4 hours, with probe ultrasound under 120W power conditions treatment three times, each time for 4min, pulse open 2s stop 4s, The temperature is maintained at 4 ° C -9 ° C, and then the solution is transferred to the dialysis bag for 12 hours of water dialysis, and then under strong stirring, a solution of 10% dithiothreitol containing the ester group contained in the nanoparticles is added, after stirring at room temperature for 12 hours, the water dialysis is again f...
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[0089] Example 3 in vitro release test of crosslinked chondroitin sulfate - rhubarbic acid - lipoic acid nanoparticle micelles of docetaxel 3
[0090] In the present embodiment, dtt simulates the hyperoxic environment in tumor tissue, and the release of the drug is determined by reverse dynamic dialysis method: take 1mL nano micelle (example 2 preparation) solution, packed in a dialysis bag with a retained molecular weight of 3500 daltons, 40ml of phosphate buffer (PBS) containing 0.2% Tween 80 pH of 7.4 as the release medium, stirring speed of 100r / min, temperature of 37±0.5 °C, Take 1 mL of dialysis medium at a predetermined time and add an equal amount of fresh release medium. After sampling, 20 μL is injected for HPLC assay, calculating the cumulative release percentage, e.g Figure 5 as shown. The results showed that compared with the docetaxel API, the crosslinked chondroitin sulfate-rivet-lipoic acid nanoparticle micelle containing docetaxate had good long-acting sustained...
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