Preparation method of rgd and peg co-modified pamam dendrimer loaded with arsenic trioxide drug delivery system

Abstract

The invention discloses a preparation method of an RGD (Arg-Gly-Asp) and PEG (Polyethylene Glycol) co-modified PAMAM (Polyamide-Amne Dendrimer) arsenic trioxide-loaded medicine delivery system. The preparation method comprises the following steps: enabling a sulfydryl group of an RGD cyclopeptide to react with a maleimide group of MAL-PEG-NHS, thus generating RGD-PEG-NHS; then reacting with a surface amino group of PAMAM, thus generating RGD-PEG-PAMAM; enabling the RGD-PEG-PAMAM to react with mPEG-NHS, thus preparing RGD-PEG-PAMAM-mPEG; enabling an arsenic trioxide solution to react with the RGD-PEG-PAMAM-mPEG, thus preparing the RGD and PEG co-modified PAMAM arsenic trioxide-loaded medicine delivery system. According to the preparation method disclosed by the invention, highly toxic traditional Chinese medicine-arsenic trioxide is firstly loaded in PAMAM; compared with an original medicine, a certain slow release action can be reflected, and the problems that ATO is poor in fat solubility, the blood-brain barrier penetration is difficult, body distribution is lack of specificity, and the like are solved; RGD is used for modifying the PAMAM, so that cellular uptake of tumor cells on the PAMAM is further increased; mPEG is used for modifying residual amino groups on the PAMAM, so that the cytotoxicity of a carrier can be further reduced.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a preparation method of a PAMAM dendrimer loaded with arsenic trioxide drug delivery system co-modified by RGD and PEG. Background technique [0002] Arsenic trioxide (ATO) is the effective active ingredient of the traditional Chinese medicine arsenic, and it is mainly used clinically for the treatment of acute promyelocytic leukemia. Some scholars have found that ATO can also inhibit the growth and induce apoptosis of a variety of solid tumor cells, and has broad-spectrum anticancer properties. However, due to the lack of specificity in the distribution of ATO in the body, it often produces serious adverse reactions to other normal tissues when the effective concentration is reached; in addition, ATO has a short half-life and is eliminated rapidly after administration, thus limiting its application in solid tumors. [0003] Polyamide-amine dendrimers (PAMAM) are a class of ...

AI Technical Summary

Problems solved by technology

[0005] In order to solve the poor fat solubility of ATO, the difficulty of penetrating the blood-brain barrier, the lack of specificity in the distribution in the body, and the high toxicity to other normal tissues when the effective concentration is reached, the therapeutic window is narrow, and the "peak-valley" fluctuation of the blood drug concentration in the brain will also cause intracranial central nervous system. Serious adverse reactions of tissues, etc., the present invention provides a preparation method of RGD and PEG co-modified PAMAM dendrimers loaded with arsenic trioxide drug delivery system, by combining RGD with PEG to co-modify PAMAM to load ATO, further reduce PAMAM At the same time of its own toxicity, it endows it with the ability to target glioma, and has a certain sustained release effect, improves the pharmacokinetic characteristics of ATO, increases bioavailability, and improves drug safety

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