Drug delivery vehicles for active customization of albumin corona and its application in pharmacy

An albumin and drug technology, applied in pharmaceutical formulations, liposome delivery, effective components of heterocyclic compounds, etc., can solve problems such as the inability to fully exert the design targeting function, and achieve the goal of overcoming the biological transmission barrier of tumors and small particle size. , the mild effect of the preparation process

Active Publication Date: 2021-06-01
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, once the targeted delivery form enters the blood, it is adsorbed by substances such as opsonins, complements, macroglobulins, and immunoglobulins in the blood, and a protein hydration crown is formed on the surface of the delivery form, which is then recognized by the reticuloendothelial system, Phagocytosis, clearance from the systemic circulation, cannot fully exert the targeted function conferred by design

Method used

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  • Drug delivery vehicles for active customization of albumin corona and its application in pharmacy
  • Drug delivery vehicles for active customization of albumin corona and its application in pharmacy
  • Drug delivery vehicles for active customization of albumin corona and its application in pharmacy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] Preparation of the maleimide-modified carrier PLGA-Mal:

[0058] Put 6-aminocaproic acid and maleic anhydride in a three-necked flask, add glacial acetic acid to dissolve, reflux for 6 h in an oil bath at 135 °C, measure a little acetic anhydride, and add it dropwise to the reaction at a rate of 1 drop / second. solution, refluxed for 2 h, and separated with a silica gel column to obtain 6-maleimidocaproic acid. Weigh 6-maleimide caproic acid and add it to a 100 mL eggplant-shaped bottle, add oxalyl chloride and stir to dissolve the sample. Reflux for 2 h in an oil bath at 70°C with stirring to obtain 6-maleimide caproyl chloride. The reaction solution was spin-dried with a rotary evaporator to remove oxalyl chloride. The obtained 6-maleimide caproyl chloride was dissolved in redistilled dichloromethane, and magnetically stirred in an oil bath at 40 °C for 15 min. At the same time, PLGA was dissolved in redistilled dichloromethane, and the constant pressure dropping fu...

Embodiment 2

[0063] The preparation method of the maleimide-modified carrier SA-PEG-Mal is described in the following steps: respectively place 6-aminocaproic acid and maleic anhydride in a three-necked flask, add glacial acetic acid to dissolve, and place them in an oil bath at 135°C Reflux for 6 h, measure a little acetic anhydride, drop it into the reaction solution at a rate of 1 drop / second, reflux for 2 h, and use a silica gel column to separate to obtain 6-maleimidocaproic acid. Weigh 6-maleimidocaproic acid into a 100 mL eggplant-shaped bottle, add oxalyl chloride and stir to dissolve the sample. Reflux for 2 h in an oil bath at 70°C with stirring to obtain 6-maleimide caproyl chloride. The reaction solution was spin-dried with a rotary evaporator to remove oxalyl chloride. The obtained 6-maleimide caproyl chloride was dissolved in redistilled dichloromethane, and magnetically stirred in an oil bath at 40 °C for 15 min. At the same time, polyethylene glycol stearic acid was disso...

Embodiment 3

[0067] Preparation of Docetaxel-loaded Nanoparticles by Emulsion Solvent Evaporation

[0068] Weigh 1 mg of docetaxel or coumarin 6, dissolve in an appropriate amount of dichloromethane, add 20 mg of PLGA-Mal or PLGA prepared in Example 1, PLGA-PEG500-Mal, PLGA-PEG2000-Mal, PLGA- PEG2000, add 5 mL of deionized water containing 0.5% PVA, sonicate the probe at 300 W for 5 min, and remove uncoated drugs by centrifugation.

[0069] The nanoparticles prepared in Example 3 were measured by dynamic light scattering and transmission electron microscopy for particle size and shape. The result is as image 3 , the particle size of the nanoparticles is about 150 nm, and the particle size distribution is narrow; the transmission electron microscope shows that the drug-loaded nanoparticles are spherical with uniform particle size.

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Abstract

The invention belongs to the field of new auxiliary materials and new dosage forms of pharmaceutical preparations, and relates to the design and application of a drug delivery system targeting endogenous albumin. The carrier material used to actively customize the albumin crown uses maleimide as the target head, polyethylene glycol as the connecting arm to increase the flexibility of the target head, and hydrophobic materials (such as PLGA, stearic acid, etc.) as the anchor fixed position. The nano-delivery preparation prepared by the carrier material can be loaded with a variety of anti-tumor drugs, and can interact with albumin receptors (SPARC, SPARC, gp60) interaction, overcome a variety of biological delivery barriers, effectively improve the accumulation of nanoparticles in tumor sites, the uptake of tumor cells and anti-tumor activity. The nano-delivery preparation has good stability, high safety and good targeting, can be used for intravenous injection, and has great market application prospects.

Description

technical field [0001] The invention belongs to the field of new excipients and new dosage forms of pharmaceutical preparations, and relates to the design and application of drug delivery carriers targeting endogenous albumin, including maleimide through polyethylene glycol (PEG) linking arms for hydrophobic The carrier structure design, synthesis and application of material modification. Background technique [0002] Cancer is also known as malignant tumor. Currently, the most effective treatment is chemotherapy, but while chemotherapy kills tumor cells, it also kills its own healthy cells. In order to reduce the toxic and side effects, tumor-targeted nano-drug delivery system came into being. The design principle of targeted nano-drug delivery system is to modify the surface of nano-delivery forms (such as nanoparticles, liposomes, micelles, nano-emulsions, nano-gels, and nano-vesicles) with small molecules, ligands, or antibodies. Overexpressed receptors or transporters...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/127A61K9/51A61K31/337A61K31/37A61K47/22A61K47/34A61K47/54A61K47/60C08G65/337C08G63/91
CPCA61K9/1271A61K9/5146A61K31/337A61K31/37A61K47/22A61K47/34C08G63/912C08G65/337C08G2650/04
Inventor 孙进李真宝何仲贵李丹孙英华
Owner SHENYANG PHARMA UNIVERSITY
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