Preparation and application of cytomembrane biomimic lipoprotein targeted nanometer drug delivery system

A nano-drug delivery system and cell membrane technology are applied in the field of preparation and application of a cell membrane biomimetic lipoprotein targeted nano-drug delivery system, which can solve problems such as limitations, achieve high safety, reduce identification and clearance, and improve bioavailability.

Active Publication Date: 2018-11-20
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although compared with infection, trauma and other diseases, the inflammatory response in adipose tissue is mild and localized, but it can still cause the infiltration of immune cells such as macrophages

Method used

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  • Preparation and application of cytomembrane biomimic lipoprotein targeted nanometer drug delivery system
  • Preparation and application of cytomembrane biomimic lipoprotein targeted nanometer drug delivery system
  • Preparation and application of cytomembrane biomimic lipoprotein targeted nanometer drug delivery system

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1-6

[0041] 1. Preparation of recombinant high-density lipoprotein drug-loaded core (rHDL / Rosi&Sild)

[0042] Weigh a certain amount of phospholipids, cholesterol, rosiglitazone and sildenafil, mix and dissolve them in an organic solvent, spin-evaporate under reduced pressure in a water bath at 37°C to form a thin film, then dry in vacuum overnight to remove excess organic solvent, and then add Appropriate amount of pure water was completely hydrated in a 40°C water bath, and ultrasonically dispersed to obtain an opalescent nanosuspension; add a certain amount of ApoA-I phosphate buffer (PBS, pH 7.4) and stir overnight, and deionized water Dialyzed for 12 hours to remove free ApoA-I to obtain the recombinant high-density lipoprotein drug-loaded inner core. The coumarin and the double drug were added together, and the above steps were repeated to obtain fluorescently labeled rHDL / Rosi&Sild.

[0043] Wherein the preparation process conditions of recombinant high-density lipoprotein ...

Embodiment 7-10

[0048] 2. Extraction of macrophage membrane (Ma)

[0049] The culture medium in the macrophage culture flask was discarded, the macrophages were blown off after washing with PBS solution (pH 7.4) for 3 times, and the supernatant was removed by centrifugation at 1000 rpm. Add cell lysate (1mM sodium bicarbonate, 0.2mM ethylenediaminetetraacetic acid and 1mM serine protease inhibitor) to the pellet, lyse at 4°C overnight, then sonicate the probe for 10min, centrifuge at 3200×g for 5-10min, discard the pellet, and The supernatant was centrifuged at 4°C at 18,000×g for 45-60 min, discarded, and the pellet was resuspended in PBS solution (pH 7.4) to obtain a macrophage membrane suspension. The DiI PBS solution was added to the prepared macrophage membrane mixture and incubated for 35 minutes, and dialyzed against deionized water for 12 hours to obtain a fluorescently labeled macrophage membrane suspension.

[0050] Wherein, the extraction process conditions of macrophage membrane ...

example 16-19

[0060] 4. Preparation of P3 peptide-modified cell membrane biomimetic recombinant high-density lipoprotein drug-loaded nanoparticles (P3-Ma / rHDL / Rosi&Sild)

[0061] The PBS solution (pH 7.4) of the P3 peptide-stearic acid conjugate was mixed with the cell membrane biomimetic recombinant high-density lipoprotein drug-loaded nanoparticle suspension in a certain proportion, incubated at 37°C for 60 minutes, and then dialyzed with deionized water for 12 hours. The free peptide is removed to obtain the P3 peptide-modified cell membrane biomimetic recombinant high-density lipoprotein drug-loaded nanoparticle. .

[0062] Among them, the preparation process conditions of the P3 peptide-modified cell membrane biomimetic recombinant high-density lipoprotein drug-loaded nanoparticles in Examples 16-19 are shown in Table 4:

[0063] Table 4 Process conditions for the preparation of P3 peptide-modified cell membrane biomimetic recombinant high-density lipoprotein drug-loaded nanoparticles...

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Abstract

The invention belongs to the field of medicinal preparations, and relates to preparation and application of a cytomembrane biomimic lipoprotein targeted nanometer drug delivery system. An anti-obesitydrug is embedded with a reconstituted high-density lipoprotein (rHDL) in a lipoprotein family to form a drug loading core, P3 peptide is modified with a cytomembrane to form a bionic shell, a bionictargeted nanoparticle used for obesity treatment is constructed, and the nanoparticle has the following characteristics: (1) the P3 peptide modified cytomembrane bionic shell has good biocompatibilityand adipose tissue targeting, so that the conditioning and phagocytosis effects of an immunity system for the nanoparticle can be reduced, the body circulation time of the drug is prolonged, and theaccumulation of the drug in adipose tissues is increased; (2) an rHDL core drug carrier has high safety and good carrying property, a lipid soluble drug can be loaded in a core embedding manner, and the lipid soluble drug can be biologically degraded completely without causing an immune reaction; and (3) the adopted anti-obesity drug can stimulate adipose tissue angiogenesis and increase white adipose tissue browning, so that the obesity is cured through synergy of the mechanism.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to the preparation and application of a cell membrane biomimetic lipoprotein targeting nano drug delivery system. Background technique [0002] Obesity is caused by the excessive accumulation of fat in the body due to the imbalance between energy absorption and energy consumption. It is a symptom of metabolic syndrome, type II diabetes (T 2 DM), cardiovascular disease, cancer and other chronic diseases, seriously affecting human life expectancy. At present, in addition to diet and exercise, clinical treatments for weight loss can be divided into two types, one is surgical treatment, such as liposuction and gastric bypass surgery, and the other is drug treatment, such as orlistat , Lorcaserin hydrochloride, etc. However, both treatment methods have side effects in varying degrees: surgical treatment has poor patient compliance, while drug treatment, such as orlistat, has se...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/42A61K47/64A61K47/46A61K9/51A61K31/519A61K31/4439A61P3/04
CPCA61K9/5169A61K9/5176A61K31/4439A61K31/519A61K47/64A61P3/04A61K2300/00
Inventor 王伟王婷婷谢梦颖
Owner CHINA PHARM UNIV
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