Preparation method of targeted reduction-sensitive nano-delivery system co-loaded with chemotherapeutic drugs and p-gp drug resistance reversal agent
A chemotherapeutic drug and drug resistance reversal technology, applied in drug delivery, drug combination, pharmaceutical formulation, etc., can solve the problems of poor water solubility of anti-tumor drugs, restrictions on the application of anti-tumor drugs, and large adverse reactions, so as to improve active targeting , reduce cytotoxicity and instability, good biocompatibility
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Embodiment 1
[0047] A method for preparing blank reduction-sensitive polymer vesicles (Blank PS), comprising the following steps:
[0048] (1) Add 25 mg PCL 7500 -ss-PEG 7500 -ss-PCL 7500 (PCL 7500 -ss-PEG 7500 -ss-PCL 7500 , see the applicant’s application on the same day for the preparation method, titled: folic acid targeted reduction-sensitive drug-loaded polymer nanomicelles and its preparation method and application) fully dissolved in methylene chloride (or a mixed organic solvent of methanol and methylene chloride) , remove the organic solvent with a rotary evaporator to form a uniform film on the inner wall of the eggplant-shaped bottle, dry the residual methylene chloride with nitrogen, put it in a vacuum drying oven, and dry it in vacuum at room temperature for 12 hours;
[0049] (2) Add 5 mL of pH7.4 phosphate buffered saline solution (PBS) to the eggplant-shaped bottle, shake to disperse the film in the solution, hydrate at 65°C for 5 h, mix well, place at room temperatur...
Embodiment 2
[0051] A method for preparing reduction-sensitive doxorubicin and paclitaxel-loaded polymer vesicles (Co-PS), comprising the following steps:
[0052] (1) Fully dissolve the amphiphilic copolymer PCL-ss-PEG-ss-PCL (25 mg) and 2.5 mg paclitaxel in dichloromethane (or a mixed organic solvent of methanol and dichloromethane), and use a rotary evaporator Remove the organic solvent to form a uniform film on the inner wall of the eggplant-shaped bottle, and dry it in vacuum for 12 hours;
[0053] (2) Prepare 300 mM ammonium sulfate aqueous solution, disperse the sample film in 5ml ammonium sulfate solution, and hydrate at 65°C for 5 hours. Mix well, place at room temperature, and sonicate for 30 min in an ice bath (5 mm probe, Ampl 30%) to obtain a stable and uniform dispersion of drug-loaded reduction-sensitive polymersomes;
[0054] (3) After the polymersome suspension was placed in a treated dialysis bag (MWCO8000-14000 Da), it was dialyzed in a sucrose solution (102.69 g sucros...
Embodiment 3
[0062] A preparation method of reduction-sensitive polymersomes loaded with Tariquidar, paclitaxel and doxorubicin (TQR-Co-PS). Including the following steps:
[0063] (1) When TQR-Co-PS was prepared, 5% (wt) TQR was added during rotary evaporation in step (1) of Example 2. TQR-Co-PS was prepared according to the same steps as (1), (2), (3), (4) and (5) of Example 2.
[0064] (2) Encapsulation efficiency of TQR-Co-PS
[0065] The prepared polymersome suspension was centrifuged at 23,000 rpm for 3 times, each time for 30 min, and washed with deionized water to remove unencapsulated drug. Finally, the precipitate was resuspended with 5 mL of water and freeze-dried. Weigh a certain amount of freeze-dried powder, dissolve it in DMSO, detect its absorbance at 480 nm with an ultraviolet spectrophotometer (UV), and quantify the concentration of doxorubicin in combination with the UV absorption standard curve at 480 nm of the doxorubicin-DMSO solution. drug content. In addition, w...
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