Calcium phosphate-lipid nano-drug co-delivery system consisting of low molecular weight heparin and prodrug of natural drug

Abstract

The invention relates to the field of pharmaceutical preparations, and relates to a calcium phosphate-lipid nano-drug co-delivery system consisting of low molecular weight heparin and a prodrug of a natural drug and a preparation method for the nano-drug co-delivery system. According to the nano-drug co-delivery system, nanoparticles prepared from a biodegradable lipid material are taken as carriers, and the phosphorylated prodrug PIC-POOH of the natural drug piceatannol (PIC) is physically entrapped, and the low molecular weight heparin (LMWH) adsorbs on the outer layers of the carriers by static electricity; and a nano preparation concentrates at a tumor site by utilizing the long circulating performance of the nano preparation and the enhanced permeability and retention (EPR) effect ofa solid tumor tissue, a related pathway for tumor cell metastasis is then regulated, angiogenesis is inhibited, and the anti-tumor metastasis action is exerted. Proved by assays, the nano-drug co-delivery system can inhibit the epithelial-mesenchymal transition (EMT) progress of tumor cells; proved by a tube formation assay, the nano-drug co-delivery system can significantly inhibit tumor angiogenesis; proved by in vivo administration evaluation, the nano-drug co-delivery system can reduce formation of lung metastasis on a mice model, and prolongs the survival time of tumor-bearing mice; and the nano-drug co-delivery system has an obvious anti-tumor metastasis effect, especially reduces triple negative breast cancer metastasis, and has high safety.

Description

technical field

[0001] The invention belongs to the field of pharmaceutical preparations, and relates to making a prodrug from a natural drug monomer with a short half-life by a chemical synthesis method and encapsulating it in a biodegradable lipid nanostructure with long circulation function, and at the same time adsorbing low molecular weight on its surface Heparin, to co-deliver the two drugs into the tumor and achieve the purpose of enhancing anti-metastasis. Background technique

[0002] Breast cancer is a kind of multiple malignant tumors all over the world, which has the characteristics of high clinical incidence, high degree of malignancy and poor prognosis. Especially for triple-negative breast cancer, the treatment effect and prognosis are poor, because this type of breast cancer cells have a high degree of migration and invasion characteristics, which makes them prone to metastasize to distant sites after forming a solid tumor in the body. 90% of patients with t...

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