Polyamide-amine (PAMAM)-based cyclodextrin functionalized derivative carrier system and application thereof

Abstract

The invention discloses a cyclodextrin functionalized derivative carrier system based on polyamide-amine and its application. The carrier system is made of cyclodextrin functionalized with polyamide-amine. The chemical The structure is as follows: Among them, cyclodextrin is β-cyclodextrin or its derivatives, γ-cyclodextrin or its derivatives, PAMAM is the core of ethylenediamine, and the end is aminated polyamide-amine (G0-G4), m =2-6; the carrier system has the function of simultaneously loading tanshinone IIA drugs, and can jointly load drugs and genes; the carrier system can be applied to in vitro gene cell transfection and treatment of arterial restenosis; the present invention is aimed at According to the characteristics of endothelial injury, a new type of carrier system is proposed, which can simultaneously load tanshinone drugs and genes, which can effectively repair the damaged endothelium, inhibit the proliferation of tissue cells, and achieve the effect of synergistic treatment. It has a good application prospect in prevention and treatment.

Description

technical field [0001] The invention belongs to the technical field of biomaterials, and relates to a polyamide-amine-based cyclodextrin functionalized derivative carrier system and its application, in particular to a preparation method of a polyamide-amine functionalized cyclodextrin cationic polymer and its Application as a carrier system. Background technique [0002] Gene therapy is a method of repairing or replacing defective or damaged genes by introducing exogenous genes into recipient cells in the body; through it, severe acquired and congenital genetic diseases such as cancer and acquired immunodeficiency can be widely treated Syndrome, cardiovascular disease, infectious disease, and chromosome-related severe comprehensive immunodeficiency, etc.; in theory, gene therapy is a simple and effective treatment method, which only needs to replace the diseased gene with a healthy gene or introduce a congenital defect In order to produce the desired protein; in fact, in or...

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Problems solved by technology

[0003] Although viral vectors have the characteristics of low pathogenicity, broad orientation, and high transfection efficiency, their high immunogenicity, risk of gene insertion mutation, transient expression of gene introduction, and low gene loading capacity have greatly affected Limiting the application of viral vectors; data show that due to serious side effects, the use of retroviral vectors for the treatment of severe combined immunodeficiency (SCID) has dropped from 28% to 19.7%; on the contrary, based on non-viral vectors The clinical experimental research on the new delivery system prepared by the system is growing rapidly. The polyamide-amine (PAMAM) biomaterial is prepared by Michael addition reaction with ethylenediamine as the core, and the primary amino group on the outer layer of the molecule is protonated to form -NH ３ ＋ group, can act as a binding site, and the tertiary amine group in the molecule acts as a "proton sponge", providing a good buffer capacity, thereby improving transfection efficiency; With the increase of the molecular weight, its toxicity is also significantly improved; it is for the above reasons that the molecular modification of PAMAM has become a research hotspot at present, aiming at bonding functional groups or molecules with functional groups to achieve The purpose of improving the original performance and broadening the scope of use

[0004] Percutaneous transluminal coronary angioplasty (PTCA) is a minimally invasive interventional therapy for the treatment of myocardial infarction and other heart diseases. Nearly 50% of the patients still had vascular restenosis within 6 months. Clinically, one or more vascular stents are usually placed to prevent postoperative vascular restenosis, but poor compliance is always a difficult problem to solve

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