Albumin nanoparticles covering pharmacological active substances as well as preparation method and application thereof

A nanotechnology of albumin and pharmacological activity, which is applied in the direction of drug combination, pharmaceutical formula, organic active ingredients, etc., can solve the problems that have not yet been reported on oral drug delivery targeting system, and achieve improved solubility, complete biocompatibility, The effect of uniform size

Active Publication Date: 2018-08-10
HUNAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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  • Albumin nanoparticles covering pharmacological active substances as well as preparation method and application thereof
  • Albumin nanoparticles covering pharmacological active substances as well as preparation method and application thereof
  • Albumin nanoparticles covering pharmacological active substances as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Preparation of Example 1 Albumin Nanoparticles (HSA NP):

[0036] (1) Mix albumin solution in the range of 150mg / mL with 30mM glutathione solution (phosphate buffer solution of glutathione, pH value is 5.0-9.0), and stir for 100min at 20°C reaction to obtain a homogeneous solution of albumin with a final protein concentration of 50 mg / mL in which the spatial structure is developed;

[0037] (2) Add 10 mM sodium selenite solution to the albumin homogeneous solution with spatial structure unfolded to obtain a final concentration of protein in the albumin solution of 30 mg / mL, stir at 4 ° C for 6 h, and obtain a crude solution of albumin nanoparticles ;

[0038] (3) Put the crude solution of albumin nanoparticles into a dialysis bag, the molecular cut-off of dialysis is not less than 1000, and dialyze in a PBS solution at 0-20°C to remove excess glutathione, selenium compounds and their by-products to obtain Albumin nanoparticles.

[0039] The albumin nanoparticles were...

Embodiment 2

[0040] Preparation of Example 2 Albumin Nanoparticles (HSA NP):

[0041] (1) Mix albumin solution in the range of 100mg / mL with 20mM glutathione solution (phosphate buffer solution of glutathione, pH value is 5.0-9.0), and stir at 30°C for 20min reaction to obtain a homogeneous solution of albumin with a final protein concentration of 50 mg / mL in which the spatial structure is developed;

[0042] (2) Add 5mM sodium selenite solution to the albumin homogeneous solution developed by the spatial structure to obtain a final albumin concentration of 20 mg / mL in the albumin solution, stir at 10°C for 8h, and obtain crude albumin nanoparticles. solution;

[0043] (3) Put the crude solution of albumin nanoparticles into a dialysis bag, the molecular cut-off of dialysis is not less than 1000, and dialyze in a PBS solution at 0-20°C to remove excess glutathione, selenium compounds and their by-products to obtain Albumin nanoparticles.

[0044] The albumin nanoparticles were digested ...

Embodiment 3

[0045] Preparation of Example 3 Albumin Nanoparticles (HSA NP):

[0046] (1) Mix albumin solution in the range of 200mg / mL with 5mM glutathione solution (phosphate buffer solution of glutathione, pH value is 5.0-9.0), and stir for 60min at 30°C reaction to obtain a homogeneous albumin solution with a final protein concentration of 80 mg / mL in which the spatial structure is expanded;

[0047] (2) Add 15 mM sodium selenite solution to the albumin homogeneous solution with spatial structure unfolded to obtain a final albumin concentration of 60 mg / mL in the albumin solution, and stir at 10 ° C for 8 hours to obtain crude albumin nanoparticles. solution;

[0048] (3) Put the crude solution of albumin nanoparticles into a dialysis bag, the molecular cut-off of dialysis is not less than 1000, and dialyze in a PBS solution at 0-20°C to remove excess glutathione, selenium compounds and their by-products to obtain Albumin nanoparticles.

[0049] The albumin nanoparticles were digest...

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Abstract

The invention belongs to the technical field of biomedicines and discloses albumin nanoparticles covering pharmacological active substances as well as a preparation method and application thereof. Thepreparation method comprises the following steps: opening an inner space structure of albumin under the action of glutathione to form protein containing a sulfydryl group active radical; adding a selenium compound and the pharmacological active substances; obtaining the albumin nanoparticles covering the pharmacological active substances by utilizing intramolecular or intermolecular sulfydryl-selenium-sulfur bond exchange reaction and sulfydryl-disulfide bond exchange reaction and elemental selenium which is loaded at inner and outer parts of a protein cavity. The method has the advantages ofsimplicity in operation; a novel albumin binding type nano-preparation has the advantages of uniform size, good dispersity and long preservation time at room temperature, and good stability in gastric acid, intestinal juice and blood serum; the solubility, dispersity, stability and bioavailability of lipid-soluble medicines are greatly improved. Meanwhile, the albumin nano-preparation keeps the solubility of albumin and a tumor targeting enriching property very well.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to albumin nanoparticles wrapped with pharmacologically active substances and a preparation method and application thereof. Background technique [0002] Albumin is a biological endogenous protein with many characteristics such as biodegradability, non-toxicity, and non-antigenicity. It is considered to be an ideal drug carrier. research direction. The combined albumin drug delivery system is a very ideal drug loading mode. Encapsulating drug molecules in albumin nanoparticles can significantly improve the stability and stability of water-insoluble drugs in aqueous solution (that is, in the blood circulation system in vivo). Solubility. At the same time, the enhanced permeability and retention effect (EPR effect) of tumor tissue can be used to make the albumin nano-drug delivery system achieve the purpose of targeted drug delivery. In addition, albumin can improve...

Claims

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Application Information

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IPC IPC(8): A61K9/14A61K47/42A61K47/04A61K31/44A61K31/337A61K31/704A61K31/4745A61K31/5377A61P35/00
CPCA61K9/143A61K9/146A61K31/337A61K31/44A61K31/4745A61K31/5377A61K31/704A61P35/00
Inventor 谭蔚泓彭咏波刘腾李雄
Owner HUNAN UNIV
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