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Functional albumin and preparation method of nano preparation of functional albumin

A nano-functionalization technology of albumin, applied in the direction of albumin peptide, serum albumin, ovalbumin, etc., can solve the problems of unanticipated clinical effect, toxic and side effects, and interference with the pharmacokinetics of anticancer drugs, etc. Achieve the effects of simple preparation method, effective treatment, and simple synthesis method

Active Publication Date: 2016-02-03
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Currently, there are few methods for reversing the drug resistance of breast cancer cells. Current studies have found that effective inhibitors of MDR include verapamil, cyclosporine A, tamoxifen, and steroid hormones (GoncalvesRS, et al., 2012; Zhang, et al., 2013 ; ZhangLH, et al., 2005), etc., but these drug resistance reversal agents interfere with the pharmacokinetics of traditional anticancer drugs, and can cause serious side effects, etc., and have not achieved the expected clinical effect so far, so they are clinically accepted. limited use

Method used

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  • Functional albumin and preparation method of nano preparation of functional albumin
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  • Functional albumin and preparation method of nano preparation of functional albumin

Examples

Experimental program
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Effect test

Embodiment 1

[0032] like figure 1As shown, under stirring conditions, add 13.875g of histamine dihydrochloride (HA) into 50ml of 50% (W / V) bovine serum albumin (BSA) neutral phosphate buffer solution, and then use 1M HCl solution to adjust When the pH value of the system reached 4.75, 4.5 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC·HCl) was finally added for catalysis, and the reaction was stirred at room temperature for 6 hours. After the reaction was terminated by adding 4M acetate buffer salt, a dialysis bag with a molecular weight cut-off of 14,000 was used for dialysis in deionized water for 3 days; filtered, frozen at -80°C, and dried to obtain imidazolized albumin (BH).

Embodiment 2

[0034] Under stirring conditions, add 17.2g of agmatine sulfate (Agm) into 50ml of 50% (W / V) human serum albumin (HSA) neutral phosphate buffer solution, and then use 1M HCl solution to adjust the pH value of the system To 4.75, finally add 4.5g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC·HCl) to catalyze, and stir at room temperature for 6h. After the reaction was terminated by adding 4M acetate buffer salt, a dialysis bag with a molecular weight cut-off of 14,000 was used for dialysis in deionized water for 3 days; filtered, frozen at -80°C, and dried to obtain guanidinated albumin (HSA-Agm).

Embodiment 3

[0036] Under stirring conditions, add 15.252g of spermine (SPE) into 50ml of 50% (W / V) human serum albumin (HSA) neutral phosphate buffer solution, and then use 1M HCl solution to adjust the pH value of the system to 4.75, Finally, 4.5 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC·HCl) was added for catalysis, and the reaction was stirred at room temperature for 6 h. After the reaction was terminated by adding 4M acetate buffer salt, a dialysis bag with a molecular weight cut-off of 14,000 was used for dialysis in deionized water for 3 days; filtered, frozen at -80°C, and dried to obtain guanidinated albumin (HSA-SPE).

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Abstract

The invention discloses functional albumin and a preparation method of a nano preparation of the functional albumin. The nano preparation of the functional albumin consists of the functional albumin, metal ions and a drug; the metal ions can simultaneously form coordination bonds with the functional albumin and the drug, and can form nanoparticles through induced self-assembly. The nano preparation, through an endocytosis mediated by an albumin receptor (SPARC) on the surface of tumor cells, can deliver the drug into the drug-resistant tumor cells, so as to effectively avoid the exocytosis effect of a p-gp pump on the drug, and then as the coordination bonds break in an acid tumor cell environment through a pH responsibility, the drug releases in cytoplast, enters cell nucleus and inlays in DNA so as to inhibit the synthesis of nucleic acid; and therefore, the growth of the tumor cells is inhibited. Through in vitro characterization, the nano preparation can achieve the relatively good pH responsibility; and through activity evaluation on a cellular level, the system is capable of effectively delivering the drug into the cells, so as to achieve relatively good pH responsive release.

Description

technical field [0001] The invention relates to a preparation method of functionalized albumin and nano-preparation thereof, and belongs to the technical field of nano-medicine and delivery carrier. Background technique [0002] Multidrug resistance (MDR) refers to the resistance of tumor cells to a certain chemotherapeutic drug after long-term exposure to it, and cross-resistance to other chemotherapeutic drugs with different structures and mechanisms of action. . Doxorubicin (Doxorubicin) is a commonly used drug in breast cancer chemotherapy. The resistance of breast cancer cells to doxorubicin is the main reason for the failure of doxorubicin chemotherapy (DetwilerA, et al., 2013), and it is also an important factor affecting the prognosis of clinical cancer patients. factor. Currently, there are few methods for reversing the drug resistance of breast cancer cells. Current studies have found that effective inhibitors of MDR include verapamil, cyclosporine A, tamoxifen, ...

Claims

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Application Information

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IPC IPC(8): A61K47/48A61K9/14C07K14/77C07K14/765C07K14/76A61P35/00
Inventor 姜虎林何玉静邢磊
Owner CHINA PHARM UNIV
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