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Preparation and applications of biologically camouflaged targeting nano drug delivering system for treating ischemic cerebral stroke

A nano-drug delivery system and a technology for ischemic stroke, which are applied in the field of preparation of biologically camouflaged targeted nano-drug delivery systems, can solve problems such as limited targeting efficiency, achieve enhanced targeting, avoid immune rejection, improve The effect of bioavailability

Active Publication Date: 2018-11-16
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Although platelet membrane-wrapped nanoparticles have a certain degree of targeting, they can be actively targeted to damaged tissue, but their targeting efficiency is limited

Method used

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  • Preparation and applications of biologically camouflaged targeting nano drug delivering system for treating ischemic cerebral stroke
  • Preparation and applications of biologically camouflaged targeting nano drug delivering system for treating ischemic cerebral stroke
  • Preparation and applications of biologically camouflaged targeting nano drug delivering system for treating ischemic cerebral stroke

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Experimental program
Comparison scheme
Effect test

Embodiment 1-7

[0041] 1. Preparation of drug-loaded core-recombinant high-density lipoprotein / ginkgolide B (rHDL / GB) nanoparticles:

[0042] Dissolve phospholipids, cholesterol, and cholesteryl ester in chloroform, and dissolve GB in methanol, then slowly add the dissolved GB to the chloroform solution, and remove the organic solvent by rotary evaporation under reduced pressure in a water bath at 37°C to form a uniform The honeycomb oil film, and continue to dry overnight in a vacuum desiccator to remove residual organic solvents. Then add pure water, decompress rotary steaming for 10-30min, probe ultrasonic, probe ultrasonic power is 200w, work for 2s, intermittent for 1s, total ultrasonic time is 10min, add apolipoprotein apoA-I by post-insertion method, at 4℃ Stir overnight, then add to a protein dialysis bag with a pore size of 50-100 kDa, dialyze overnight in PBS solution (pH 7.4) at 4°C to obtain rHDL / GB.

[0043] Wherein, the process conditions used to prepare the drug-loaded core in...

Embodiment 8-10

[0048] 2. Extraction steps of platelet membrane:

[0049] The platelet membrane was extracted by freezing and thawing, the collected blood was placed in an anticoagulated centrifuge tube for 30 minutes, centrifuged at 100g for 20 minutes to absorb the supernatant, and PBS buffer containing 1mM EDTA and 2mM prostaglandin E1 was added dropwise to prevent platelet activation. Centrifuge at 800g for 20min to discard the supernatant, and resuspend the platelets in isotonic PBS solution (pH 7.4), freeze them in a -80°C refrigerator for 6-12h, then thaw at 25°C for 1-6h, repeat 3 times, the freeze-thaw solution was centrifuged at 3000r / min for 30min, the platelet fragments and supernatant were collected respectively, the platelet fragments were suspended in PBS solution (pH 7.4), washed and centrifuged, ultrasonically crushed with a 50 / 60Hz probe ultrasonic instrument for 5min, 3000r / min and collect the supernatant.

[0050] Table 2 is the process condition that the platelet membra...

Embodiment 9-12

[0053] 3. Preparation of bio-camouflaged nano-drug delivery system-CITP-PEG-SA / platelet membrane / recombinant high-density lipoprotein / ginkgolide B (CITP-PEG-SA / PM / rHDL / GB) nanoparticles:

[0054] (1) Mix the above-mentioned prepared drug-loaded core with the extracted platelet membrane according to the volume ratio of 1:1 to 1:5, and repeatedly extrude through an extrusion device containing a polyester carbonate membrane with a pore size of 400 nm 3 to 9 times to realize the fusion of platelet membranes and nanoparticles, and high-speed centrifugation to remove excess platelet membranes to obtain drug-loaded nanoparticles.

[0055] (2) Dissolve CITP-PEG-SA in PBS solution (pH 7.4), then add the solution dropwise to drug-loaded nanoparticles and stir overnight, then add it to a protein dialysis bag with a pore size of 1000-3500Da, and dialyze in PBS solution Get CITP-PEG-SA / platelet membrane / recombinant high-density lipoprotein / ginkgolide B nanoparticles (CITP-PEG-SA / PM / rHDL / GB...

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Abstract

The invention relates to preparation and applications of a biologically camouflaged targeting nano drug delivering system for treating ischemic cerebral stroke. The nano drug delivering system is compose of a drug, an inner core drug carrier, a biologically camouflaging shell, and a target finding material, wherein the drug is bilobalide B, the inner core drug carrier is recombinant high density lipoprotein, a drug is physically embedded into the drug carrier to form a drug loaded inner core; the biologically camouflaging shell is a blood platelet membrane, the drug loaded inner core is embedded in the blood platelet membrane in a co-extrusion mode to form a biomimetic drug loaded nano particle; the target finding material is a cerebral ischemia targeting peptide (CITP), and the CITP is used to modify the surface of the biomimetic drug loaded nano particle to form the biologically camouflaged targeting nano drug delivering system. Recombinant high density lipoprotein is used to wrap bilobalide B to form the drug loaded inner core, a blood platelet membrane and a blood platelet with a CITP modified surface are taken as the biomimetic shells to construct a nano particle for treatingischemic cerebral stroke, the circulation time of the nano particle in human body is prolonged, and the nano particle has a good targeting performance.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical preparations, and relates to the preparation and application of a biological camouflage targeting nano drug delivery system for the treatment of ischemic stroke. Background technique [0002] Cerebrovascular disease, also known as stroke, is a disease caused by a variety of etiologies that cause cerebrovascular lesions and lead to brain function defects. Clinically, about 80% of strokes are ischemic strokes, which are mainly due to the sclerosis and stenosis of cerebral arteries and vessels gradually develop into obstruction; it can also be blocked when the emboli in the heart part fall off and flow along the blood to the blood vessels in the brain, thereby Caused by interruption of cerebral blood flow supply, brain tissue hypoxia or necrosis. At present, there are many methods for the clinical treatment of ischemic stroke, such as anti-platelet aggregation, promoting blood circulation and...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/50A61K47/42A61K47/46A61K31/365A61P9/10A61P7/02A61P29/00A61P9/00
CPCA61K9/0019A61K9/5052A61K9/5063A61K31/365A61P7/02A61P9/00A61P9/10A61P29/00
Inventor 王伟苏杨楠
Owner CHINA PHARM UNIV
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