Agent-enriched nanoparticles based on hydrophilic proteins

A nanoparticle and protein technology, applied in the field of nanoparticles loaded with active agents, can solve the problems of average particle size increase, toxicity effects, particle efficacy and side effects, etc.

Inactive Publication Date: 2009-05-27
LTS LOHMANN THERAPIE-SYST AG
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] However, known polybutylcyanoacrylate nanoparticles that cross the blood-brain barrier have the following drawbacks: polysorbate 80 is not of physiological origin, and the transport of nanoparticles across the blood-brain barrier may be due to the toxic effects of polysorbate 80
For example, its use is complicated in terms of the production of nanoparticles and may also lead to immune effects or other side effects
Furthermore, particle systems comprising the avidin-biotin system tend to agglomerate when stored for prolonged periods of time, which leads to an increase in the average particle size and negatively impacts the efficacy of the particles

Method used

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  • Agent-enriched nanoparticles based on hydrophilic proteins

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Embodiment

[0041] To prepare HSA nanoparticles by desolvation, 200 mg of human serum albumin was dissolved in 2.0 ml of 10 mM NaCl solution, and the pH of the solution was adjusted to 8.0. 80 ml of ethanol was added dropwise to the solution at a rate of 1.0 ml / min under stirring. This desolvation step resulted in the formation of HSA nanoparticles with an average particle size of 200 nm.

[0042] The nanoparticles were stabilized by adding 235 μl of 8% glutaraldehyde solution. After incubation for 12 hours, the nanoparticles were purified by three centrifugations and redispersion first in purified water followed by PBS buffer (pH 8.0).

[0043] To activate the nanoparticles, 500 μl of the crosslinker NHS-PEG3400-Mal solution (60 mg / ml in PBS buffer 8.0) was added to 2.0 ml of the nanoparticle suspension (20 mg / ml in PBS buffer 8.0) under stirring middle) and incubated at room temperature for 1 hour. After the incubation period, the PEG-modified nanoparticles were purified using purifi...

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Abstract

The invention relates to agent-enriched nanoparticles that are based on a hydrophilic protein or a combination of hydrophilic proteins in which functional proteins or peptide fragments are bound to the nanoparticles via polyethylene glycol-alpha-maleic acid imide-rou-NHS esters. Also disclosed are methods for producing said nanoparticles and the use thereof.

Description

technical field [0001] The present invention relates to active agent-loaded nanoparticles based on one hydrophilic protein or a combination of multiple hydrophilic proteins in which functional proteins or peptide fragments are treated with polyethylene glycol-α-maleimide-ω -NHS esters bound to nanoparticles. More specifically, for the transport of drugs or bioactive agents across the blood-brain barriers, the present invention relates to active agent-loaded nanoparticles based on at least one hydrophilic protein and functional proteins or peptides therein Fragments, preferably apolipoproteins, are bound to nanoparticles via polyethylene glycol-α-maleimide-ω-NHS esters. Background technique [0002] The term "nanoparticle" is understood to mean particles with an average size between 10 nm and 1000 nm and composed of artificial or natural macromolecular substances, to which drugs or other biologically active substances can be bound by covalent, ionic or adsorptive bonds , or...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/48A61K31/451
CPCA61K31/451A61K47/48238B82Y5/00A61K47/48892A61K47/48284A61K47/62A61K47/643A61K47/6931A61P25/00A61P25/04A61K47/50
Inventor 约尔格·克洛伊特尔克劳斯·朗热克思廷·米夏埃利斯泰利·希克马特拉塞巴斯蒂安·德莱塞
Owner LTS LOHMANN THERAPIE-SYST AG
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