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Anticancer drug nanosphere and preparation method thereof
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An anti-cancer drug and nano-microsphere technology, which is applied in the preparation of sugar derivatives, drug combinations, anti-tumor drugs, etc., can solve the problems of low drug loading rate, achieve high drug loading rate, easy availability of raw materials, and reduce cytotoxicity. Effects of side effects
Active Publication Date: 2020-08-14
深圳市缘泰科技有限公司
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The nano-microspheres prepared by dialysis have better dispersion and uniform particle size, but for surfactants with less hydrophobicity, the drug-loading rate is low when preparing nano-microspheres by this method
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[0030] The invention provides a method for preparing anticancer drug nanospheres, the preparation method comprising:
[0031] 1) In the presence of dark conditions and organic solvents, triethylamine and doxorubicin hydrochloride DOX·HCL are subjected to a contact reaction, and finally freeze-dried to obtain hydrophobic doxorubicin DOX;
[0032] 2) Emulsifying the DOX solution and the peptide solution to obtain colostrum balls;
[0033] 3) Carrying out the double emulsification reaction of the colostrum ball and the stabilizer to obtain the double emulsification ball;
[0034] 4) Dialyze the double-emulsified ball, then centrifuge the dialyzed system to get the supernatant, and finally freeze-dry to obtain the new anticancer drug delivery system;
[0035] Wherein, the peptide solution is selected from at least one of P10-L3 peptide solution, P10-V3 peptide solution, and P10-F3 peptide solution.
[0036] In the present invention, the specific type of solvent can be selected i...
Embodiment 1
[0063] a. Under the condition of avoiding light, add 1mL triethylamine and 10mg DOX·HCL to 4mL ACM / DCM (1:1 volume ratio), then put it in a magnetic stirrer at 20°C, at 1000r / min, Contact reaction for 2 hours, and finally freeze-drying (temperature at -80°C, pressure at 999Pa, drying time at 12 hours) to obtain DOX. At the same speed and temperature, inject 2 mL of DOX solution (1 mg / mL, The solvent is ACM / DCM mixture with a volume ratio of 1:1) dropwise (dropping time is 15s) into 8mL P10-L3 peptide solution (the concentration of the peptide is 1mg / mL, the solvent is ACM with a volume ratio of 1:1 / DCM mixed liquor), reacted for 12h to prepare colostrum balls (surfactant-DOX).
[0064] b. Use a syringe with a 0.34mm needle to drop 10mL of colostrum balls (dropping time is 30s) into 50mL of PVA solution with a mass fraction of 2%, and re-emulsify at a speed of 1000r / min and a temperature of 20°C React for 4min; put 60mL double emulsification ball solution into a 1000Da dialys...
Embodiment 2
[0066] The P10-V3-DOX microspheres were prepared according to the method of Example 1, except that the P10-L3 peptide solution was replaced with the P10-V3 peptide solution.
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Abstract
The invention discloses an anticancer drug nano-microsphere and a preparation method thereof. The preparation method comprises: 1) conducting a contact reaction with triethylamine and doxorubicin hydrochloride DOX·HCL under light-proof conditions and in the presence of an organic solvent , and finally lyophilized to obtain hydrophobic doxorubicin DOX; 2) DOX solution and peptide solution were emulsified to obtain colostrum balls; 3) colostrum balls and stabilizers were double-emulsified to obtain double-emulsified balls; 4) Dialyze the double emulsified ball, then centrifuge the dialyzed system to get the supernatant, and finally freeze-dry to obtain the new anticancer drug delivery system; the peptide solution is selected from P10‑L3 peptide solution, P10‑V3 peptide solution, P10‑ At least one of the F3 peptide solutions. The anticancer drug nano microsphere has excellent hydrophobic effect, drug loading rate and targeting effect, and the preparation method has the advantages of more thorough removal of organic solvents, more uniform particle size, and lower toxicity and side effects on cells.
Description
technical field [0001] The invention relates to drug nano-microspheres, in particular to an anticancer drug nano-microsphere and a preparation method thereof. Background technique [0002] Tumor has become a frequently-occurring and common disease that seriously threatens human life and health. Chemotherapy is one of the main methods for clinical treatment of tumors. However, while chemotherapy drugs kill cancer cells, they also kill a large number of normal cells, causing problems such as high toxicity and side effects, poor compliance, and difficulty in controlling metastases. [0003] P10 peptide (DGRGGGAAAA) is a novel surfactant with targeting effect. Studies have shown that, using doxorubicin (DOX) as a drug model, at a concentration of 20 μg / mL, the cell inhibition rate of P10-DOX nanospheres is 2.89 times higher than that of free DOX. This result shows that the effect of P10 peptide as a drug transport carrier is close to that of the more mature amphiphilic polymer...
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