Targeted drug delivery system based on milk exosome

A technology of exosomes and targeting ligands, applied in drug combinations, antineoplastic drugs, gene therapy, etc., can solve problems such as complex operations, high costs, and restrictions on mass production of exosomes, to achieve enhanced drug efficacy, Promote application and achieve effective accumulation

Pending Publication Date: 2020-04-17
AFFILIATED HOSPITAL OF JIANGNAN UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Due to the complicated operation and high cost brought by

Method used

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  • Targeted drug delivery system based on milk exosome
  • Targeted drug delivery system based on milk exosome
  • Targeted drug delivery system based on milk exosome

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Example 1 The milk exosome drug-carrying system modified by hyaluronic acid

[0033] In this embodiment, the molecule with tumor targeting function is hyaluronic acid (HA), and the loaded drug is doxorubicin.

[0034] Preparation of targeting ligands

[0035] Take 45mg of HA (MW 30kDa) and 0.5mgEDCI (1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride), 0.2mgNHS (N-hydroxysuccinimide) in 4 ℃ reaction for 4h to form the activated ester form of HA, and then with 4.1mg of DSPE-PEG 2000 -NH 2 (Dipalmitoylphosphatidylethanolamine-polyethylene glycol-amino, purchased by Huateng Pharmaceutical Company.) Reacted at room temperature for 12h, the solvent was DMF, and the solution after the reaction was dried with nitrogen, redissolved in PBS, and self-loaded with LH20 Column purification, the purified product was verified by NMR and stored at -20°C to obtain the targeting ligand DSPE-PEG 2000 -HA.

[0036] Preparation of milk exosomes

[0037] Separate milk, 13,000g,...

Embodiment 2

[0056] Example 2 The milk exosome drug-carrying system modified by folic acid

[0057] In this embodiment, the molecule with tumor targeting function is folic acid (FA), and the loaded drug is doxorubicin.

[0058] Preparation of targeting ligands

[0059] DSPE-PEG 2000 -FA purchased from Huateng Pharmaceutical Company

[0060] Preparation of milk exosomes

[0061] Separate milk, 13,000g, 4°C, centrifuge for 30 minutes, after centrifugation, remove the upper layer of fat, bottom casein residue and cell debris, collect the middle part of the emulsion to obtain skim milk; skim milk and distilled water in a volume ratio of 1:1 Dilute; use 2M hydrochloric acid to adjust the pH value of the solution to 4.6, so that the casein in the solution is precipitated; it is evenly distributed, 10,000g, and centrifuged for 40 minutes (centrifugal force is 0.7×10 4 g), discard the protein precipitate at the bottom, collect the upper layer of whey and pass it through a 0.22 μm filter membra...

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Abstract

The invention, which belongs to the field of pharmaceutical engineering, particularly relates to a targeted drug delivery system based on milk exosome. The invention discloses a targeted drug deliverysystem based on milk exosome. The construction method comprises: a targeted ligand with an aliphatic chain at one end is modified on the surface of the drug delivery milk exosome, and the other end of the targeted ligand is a molecule capable of being specifically bound with an overexpressed receptor on the surface of a tumor cell. The modified drug delivery milk exosome disclosed by the invention can be bound with cancer cells in a targeting manner, so that the uptake of the cancer cells is enhanced and the effect of specifically killing tumor cells is realized.

Description

technical field [0001] The invention belongs to the field of pharmaceutical engineering, and in particular relates to a targeted drug-loading system based on milk exosomes. Background technique [0002] Exosomes are natural nanoscale vesicles secreted by cells, which can play a role in intercellular communication. Their hollow structure and good biocompatibility make exosomes widely used in nano drug delivery systems. Due to the complicated operation and high cost brought about by cell culture, the mass production of exosomes is limited. Studies have shown that extracting exosomes from milk can solve this problem, and even have the potential for oral drug delivery due to the tolerance of milk exosomes to the gastrointestinal environment. [0003] Targeted modification of the drug-loaded system usually selects molecules that can specifically bind to overexpressed receptors on the surface of tumor cells, and anchors them on the surface of the drug-loaded system to achieve the...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K47/54A61K31/704A61K48/00A61P35/00
CPCA61K31/704A61K48/005A61K47/6901A61K47/544A61P35/00
Inventor 黄朝晖吴志猛李丹姚苏芮苑曼曼周志昉殷媛
Owner AFFILIATED HOSPITAL OF JIANGNAN UNIV
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