PEGylated dendritic macromolecule drug carrier and preparation method thereof

Abstract

The invention relates to a preparation method of a PEGylated dendritic macromolecule drug carrier, which comprises the following steps of: mixing trimethylolpropane triacrylate and ethylenediamine inan ice-water bath, reacting alternately in an organic solvent in a protective atmosphere at the reaction temperature of 25-60 DEG C, obtaining an amino-terminated dendritic macromolecule using ethylenediamine as a core or an acrylate-terminated dendritic macromolecule using trimethylolpropane triacrylate as a core; dissolving PEG, p-nitrophenyl chloroformate and triethylamine in an organic solvent, reacting at 20-30 DEG C, and obtaining PEGylated p-nitrophenyl carbonate after the reaction is complete; reacting the amino-terminated dendritic macromolecule using the ethylenediamine as the core or acrylate-terminated dendritic macromolecule using the trimethylolpropane triacrylate as the core with the PEGylated p-nitrophenyl carbonate in an organic solvent at a reaction temperature of 20-30 DEG C. The method is easy to operate, high in yield and low in cost; and the prepared drug carrier has excellent drug carrying performance on drugs which are difficult in dissolving in water.

Description

technical field [0001] The invention relates to the technical field of dendritic macromolecule synthesis technology and drug carrier, in particular to a PEGylated dendritic macromolecule drug carrier and a preparation method thereof. Background technique [0002] In recent years, the use of nano drug delivery systems (NDDSs) to enhance the efficacy of anticancer drugs in vivo has been recognized by more and more researchers, making it a new type of drug delivery system. NDDSs can increase the permeability of biomembrane and the solubility of fat-soluble drugs, which not only has the advantages of good stability, targeted delivery of drugs to tumor sites and slow release, but also reduces the dosage, frequency of administration, and harm to other organs. device damage, broad application prospects. There are various types of NDDSs nanocarriers, including liposomes, polymer nanoparticles, polymer micelles, carbon nanotubes, solid lipid nanoparticles, vesicles, and dendrimers. ...

AI Technical Summary

Problems solved by technology

However, the particle size distribution of the polymer drug carrier structure is too wide, especially during the carrier formation process, when the polymer concentration is lower than the critical concentration, the dilution of the drug carrier itself will seriously affect its drug loading effect

Chinese patent CN106943601 A reports a carrier and a preparation method for improving protein bioavailability and water solubility of poorly soluble drugs, including the synthesis of polyethylene glycol-polybenzyl glutamate block copolymer, the synthesis of aminolysis products, and the synthesis of linear polybenzyl glutamate. Synthesis of ethylene glycol-brush polybenzyloxycarbonyl lysine block copolymer, synthesis of linear polyethylene glycol-brush polybenzyloxycarbonyl lysine and polylysine block copolymer; the advantage is to solve The bioavailability of protein drugs and the water solubility of insoluble drugs can be solved, so that a variety of injections can be prepared, which has the characteristics of improving protein bioavailability, increasing water solubility of hydrophobic drugs, reducing injection frequency, reducing the economic burden of clinical patients, and enhancing drug efficacy. , but its preparation process is complex and its application prospects are limited

[0006] At present, there is no research on acrylate-terminated and amino-terminated dendrimers, PEGylated acrylate-terminated and amino-terminated dendrimers to load insoluble anticancer drugs such as camptothecin and L-shikonin. Published reports and patent applications

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