Preparation method of As2O3 albumin nano medicine

Abstract

The invention discloses a preparation method of an As2O3 albumin nano medicine. The preparation method includes the following steps: 1) dissolving As2O3 powder in a NaOH solution and regulating the pH with diluted hydrochloric acid to prepare an As2O3 solution for drug supporting of albumin in later use, dissolving human serum albumin marked by folic acid molecules in a Dulbecco's phosphate buffer liquid without calcium and magnesium ions to obtain a human serum albumin solution, and adding a disulfide bond reducing agent to the human serum albumin solution and performing a reaction in a water bath pot with gentle stirring to obtain the albumin solution treated by the disulfide bond reducing agent; 2) adding the As2O3 solution to the albumin solution treated by the disulfide bond reducing agent, and stirring the mixture at room temperature to obtain an As2O3 albumin mixed solution; and 3) dialyzing the As2O3 albumin mixed solution in a dialysis bag at low temperature with a D-PBS solution to remove residual As2O3, disulfide bond reducing agent and side products thereof to obtain the As2O3 albumin nano medicine.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to the construction and anticancer application of arsenic trioxide albumin drug-loaded nanometer system. Background technique [0002] Arsenic trioxide (As 2 o 3 , ATO) is the main component of traditional Chinese medicine arsenic. In the field of modern medicine and traditional Chinese medicine, it has been widely used in the treatment of various diseases such as malignant tumors, especially in the treatment of acute promyelocytic leukemia (APL). Significant efficacy of complete remission, induction of APL differentiation and apoptosis. Natural arsenic compounds have been used clinically as medicines for more than 2,400 years. Recent studies have shown that ATO also has a strong anti-tumor effect on chronic myelogenous leukemia and malignant solid tumors, but there are some problems in the treatment of non-APL by ATO alone: ​​(1) The aqueous form of ATO is arseno...

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Problems solved by technology

Recent studies have shown that ATO also has a strong anti-tumor effect on chronic myelogenous leukemia and malignant solid tumors, but there are some problems in the treatment of non-APL by ATO alone: ​​(1) The aqueous form of ATO is arsenous acid (As(OH) 3 ), easy to pass through the phospholipid bilayer, which severely restricts the retention of ATO in the cell; (2) 85% to 95% of ATO in the organism first combines with the hemoglobin in the blood and then distributes to other tissues, so in the organism The distribution is fast, the half-life of arsenic in plasma is short (about 35 minutes), and it will be quickly cleared in a short time after administration, causing toxic and side effects at the same time; (3) the existing ATO anti-cancer drug delivery route is intravenous drip, due to Circulation can make ATO diffuse to the surrounding tissues, which not only makes the concentration of the drug reaching the tumor site relatively low, but also brings serious adverse reactions to patients; (4) ATO's anticancer effect depends on its strong toxicity, Therefore, it is limited to keep the dose relatively low when it is used directly, which limits the low anticancer efficacy index of ATO; when the therapeutic dose is relatively high for chronic random leukemia and other malignant tumors, the simple ATO brings The toxicity and side effects are more significant, which strictly limits the promotion and use of its clinical treatment

However, the stability of liposome is not good enough, and it is easy to leak after encapsulating the drug, which will bring certain toxic and side effects, and the encapsulation technology of ionic ATO is more difficult than conventional organic small molecule drugs.

In addition, traditional sustained-release preparations have no targeting, and are distributed in various organs of the body after administration, which greatly weakens the anticancer efficacy of the drug; at the same time, the nanometer size of liposomes is much larger than that of small organic molecules or proteins ( Usually in the range of 100-200nm), after the liposome drug-loaded system enters the human body, it is difficult to escape the phagocytosis of foreign matter by macrophages in the immune system, resulting in a far lower dose that finally reaches the lesion to exert its drug effect

In addition, the preparation process of liposome is relatively complicated, and it is necessary to adjust the ratio of liposome composition and organic solvent according to the molecular properties of the drug.

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