Preparation method of arsenic trioxide preparation with positive charge and liver targeting effect
A positively charged arsenic trioxide technology, applied in the field of biomedicine, can solve the problems of limited application and short half-life, and achieve the effect of controllable shape, high drug loading and uniform size
Active Publication Date: 2018-08-17
YANGZHOU UNIV
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However As 2 o 3 The half-life in the body is short, and it will be cleared quickly after administration; in addition, high doses of As 2 o 3 It will bring toxic and side effects such as nerve paralysis and liver failure, which limits its clinical application
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[0038] 1. Preparation of As 2 o 3 -PLGA / PLCNPs:
[0039] 1. Synthesis of polyethylene glycol / lactobionic acid-chitosan PEG / LA-CS (referred to as: PLC):
[0040] Weigh 1g chitosan (CS) and dissolve it in 6 mL acetic acid (2%), add 20 mL TEMED HCL buffer solution (pH=4.7) to dilute, stir for 20 min, then add 3.83 mg EDC and 2.30 mg NHS respectively, after 30 min Add 0.16mg of polyethylene glycol (mPEG) and 1.43mg of lactobionic acid (LA), stir and react at 35°C for 36h, strictly control pH 4-6 during the reaction process, the reaction process is as follows figure 1 shown. The crude product was dialyzed in a dialysis bag for 4 days, and freeze-dried to obtain polyethylene glycol / lactobionic acid-chitosan (PLC).
[0041] 2. Preparation of As 2 o 3 -PLGA / PLC NPs:
[0042] Such as figure 2 Shown:
[0043] (1) put As 2 o 3 Soluble in sodium hydroxide aqueous solution with a mass percentage of sodium hydroxide of 4% to form As 2 o 3 60 mg / mL As 2 o 3 Sodium hydroxide sol...
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Abstract
The preparation method of the novel arsenic trioxide preparation with positive charge and liver targeting effect belongs to the technical field of biomedicine. In the present invention, the sodium hydroxide solution of As2O3 is used as the internal water phase, and the chloroform solution of lactic acid-glycolic acid is used as the oil phase. The oil phase encapsulates the inner water phase to form W / O colostrum. Then take the emulsifier aqueous solution containing polyethylene glycol / lactose-chitosan as the external water phase. Using biodegradable and biocompatible lactic acid-glycolic acid copolymer as encapsulation material, As2O3-PLGA / PLC NPs were prepared by double emulsification-solvent evaporation method, with uniform nanoparticle size, good dispersion, encapsulation efficiency, High drug loading, stable release in vitro, good anti-tumor performance in vivo and in vitro, and a certain liver targeting function, so that As2O3 can directly target the tumor site of liver cancer and realize the controllable drug delivery at the tumor site release, improving the healing effect.
Description
technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a preparation technology of arsenic trioxide preparation with positive charge and liver-targeting effect. Background technique: [0002] Arsenic trioxide (As 2 o 3 ) is the main active ingredient of the traditional Chinese medicine arsenic, and its injection was first used to treat acute promyelocytic leukemia. Studies have found that arsenic trioxide not only has a significant effect on acute promyelocytic leukemia, but also has a good inhibitory effect on solid tumors. However As 2 o 3 The half-life in the body is short, and it will be cleared quickly after administration; in addition, high doses of As 2 o 3 It will bring toxic and side effects such as nerve paralysis and liver failure, which limits its clinical application. Contents of the invention [0003] The object of the present invention is to overcome anticancer drug As 2 o 3 Due to the defect...
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IPC IPC(8): A61K9/52A61K33/36A61K47/10A61K47/34A61K47/36A61P35/02C08B37/08
CPCA61K9/5146A61K9/5161A61K9/5192A61K33/36C08B37/003
Inventor 宋晓丽王娟闫彩凤朱爱萍郭荣
Owner YANGZHOU UNIV