Preparation method of reductive-response amphipathic wormlike monomolecular prodrug

Abstract

The invention discloses a preparation method of reductive-response amphipathic wormlike monomolecular prodrug. On the basis of linear structure of glucan, stimulus response of high-concentration glutathione in tumor cells is utilized to promote splitting of disulfide bonds of the amphipathic wormlike monomolecular prodrug to realize synchronous release of camptothecin (CPT) which is antitumor drug so as to act on a tumor position. The preparation method includes following steps: (1), preparing camptothecin monomer: specifically introducing disulfide-bond camptothecin CPT-SS; (2), preparing a drug initiator DEX-Br; (3), polymerizing the camptothecin monomer CPT-SS on the initiator through atom transfer radical polymerization (ATRP) to obtain a DEX-CPT-SS hydrophobic intermediate product; (4), utilizing ATRP to polymerize polyethylene glycol methacrylate (OEGMA) to obtain amphipathic segmented polymer DEX-CPT-OEGMA-SS named as DCO-SS. The obtained amphipathic wormlike monomolecular prodrug can directly form a drug monomolecular micelle in an aqueous phase, has the advantages of high drug loading capacity (higher than 23wt%), high micelle stability, sensitive stimulus-response drug release, high biocompatibility and low toxic and side effect on normal tissue. The problem that hydrophobic drug is low in molecular solubility is solved effectively, and an efficient drug delivery carrier is provided.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to a preparation method of a reduction-responsive amphiphilic worm-like single-molecule prodrug and its application in the field of drug treatment of cancer. Background technique [0002] Dextran (Dextran, also known as dextran, a polysaccharide, molecular formula (C6H10O5) n, CAS number: 9004-54-0), dextran can replace a part of whole blood during blood transfusion, as a plasma volume expander ( called plasma substitute). Commercial plasma substitutes are partially hydrolyzed dextran dissolved in normal saline. Therefore, dextran has good biocompatibility, is harmless to the human body, and is biodegradable. It is a good carrier material for anticancer drugs. Camptothecin (CPT, chemical structure: C 20 h 16 N 2 o 4 , CAS No.: 7689-03-4, relative molecular weight: 348.43) is a plant anticancer drug extracted from camphor trees distributed in south-central and sout...

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Problems solved by technology

[0004] In view of this, one of the objectives of the present invention is to provide a reduction-responsive amphiphilic worm-like single-molecule prodrug for the defects of poor selectivity, uncontrollable release, and low drug loading rate of existing single-molecule anti-tumor drugs. Preparation method and its application in the field of drug treatment of cancer

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