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Death ligand antibody conjugated polyethylene glycol modified lipid nano drug delivery system and its application

A polyethylene glycol and death ligand technology, applied in the field of biomedicine, can solve problems such as the targeting of ischemic lesions that are rarely considered, and achieve the goal of improving the efficiency of brain entry, good biocompatibility, and increasing the amount of distribution Effect

Active Publication Date: 2015-10-21
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The current drug delivery system design mainly focuses on improving the bioavailability of drugs and the efficiency of crossing the blood-brain barrier, but rarely considers entering the brain in the ischemic lesion area targeting

Method used

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  • Death ligand antibody conjugated polyethylene glycol modified lipid nano drug delivery system and its application
  • Death ligand antibody conjugated polyethylene glycol modified lipid nano drug delivery system and its application
  • Death ligand antibody conjugated polyethylene glycol modified lipid nano drug delivery system and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Embodiment one Establishment of brain-targeted nano drug delivery system coupled with Fas ligand antibody

[0030] 1.1 Synthesis of rhodamine stearylamine

[0031] Dissolve 25.14g of stearylamine and 50mg of Rhodamine B in 6mL of ethanol, and react in the dark for 24 hours under magnetic stirring at 400rpm, then add 50mL of water, and freeze-dry. The freeze-dried sample was washed with 5 mL of distilled water, and then filtered through a 0.45 μm filter membrane. Dry at room temperature to obtain rhodamine stearylamine.

[0032] 1.2 Preparation of drug-loaded lipid nanoparticles

[0033] Dissolve 13.5 mg of glyceryl monostearate, 8.5 mg of medium-chain triglycerides, 1.5 mg of rhodamine stearylamine, and 5 mg of butylphthalide in 1 ml of ethanol, heat and stir in a water bath at 70°C to dissolve. Slowly inject the above solution into 9 ml of 0.1% Tween 80 aqueous solution while hot, and stir magnetically at 400 rpm for 5 minutes to obtain a 3 mg / ml lipid nanoparticl...

Embodiment 2

[0038] Embodiment two Evaluation of physicochemical properties of brain-targeted lipid nanoparticles coupled with Fas ligand antibody

[0039] 2.1 Determination of particle size and potential of lipid nanoparticles

[0040] Take 0.5 ml of the unmodified, Fas ligand antibody-coupled and PEG-modified two drug-loaded lipid nanoparticles prepared above, dilute 10 times with deionized water, and use a particle size and surface potential analyzer (Zetasizer, 3000HS, Malvern Instruments ) to measure the particle size and potential of the two lipid nanoparticles, respectively.

[0041] The results showed that the diameter of antibody-modified drug-loaded nanoparticles (60.97±7.95nm) was larger than that of non-antibody-modified drug-loaded nanoparticles (38.23±3.22nm), and the space diameter of nanoparticles after antibody modification increased; resemblance.

[0042] 2.2 Drug encapsulation efficiency and drug loading

[0043] The content of butylphthalide in lipid nanoparticl...

Embodiment 3

[0052] Embodiment Three Pharmacodynamics of brain-targeted drug-loaded nanoparticles against ischemic brain injury

[0053] 3.1 The pathological model of ischemic brain injury was established by the method of middle cerebral artery suture embolization in mice

[0054] The model of cerebral microvascular ischemia injury was established by using the focal middle cerebral artery occlusion / reperfusion (MCAO) model in mice: the mice were anesthetized with 3% isoflurane, fixed in supine position, and the neck was disinfected , Carotid median incision, separation of the left common carotid artery, internal carotid, external carotid artery. The proximal end of the common carotid artery and the external carotid artery were ligated, the internal carotid artery was clamped with an arterial clamp, a small opening was cut in the common carotid artery, and a nylon thread plug (smooth spherical surface, thread plug diameter 0.26 mm) was inserted horizontally toward the end of the internal...

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Abstract

The invention provides a death ligand antibody coupled polyethylene glycol modified lipid nano drug delivery system, which is delivered by preparing polyethylene glycol (PEG) modified and death ligand (Fas ligand) antibody coupled lipid nanoparticles Combined with the experimental animal model of ischemic brain injury, the pharmacodynamic indicators of the brain-targeted nano-drug delivery system coupled with Fas ligand antibody were evaluated from the whole animal level, which proved its good brain-targeting and brain-deficient drug delivery system. Targeting of the blood area. From the reduction of infarct size and the improvement of animal nerve function damage and other indicators, it is proved that the drug delivery system can reduce the drug dose and improve the efficacy of the drug, so as to provide a more efficient and low-toxic drug delivery system for the clinical treatment of ischemic stroke. .

Description

technical field [0001] The invention belongs to the technical field of biomedicine and relates to a targeted drug delivery system, in particular to a brain-targeted drug delivery system for treating ischemic stroke and sequelae of stroke, in particular to a death ligand (Fas ligand) Antibody-coupled polyethylene glycol (PEG) modified lipid nano drug delivery system and its preparation method and application. Background technique [0002] Cerebrovascular disease is a common and frequently-occurring disease that endangers human life and health. Due to the aging population and the prevalence of cardiovascular risk factors, stroke has become the number one cause of death and disability in my country, and the mortality rate is much higher than that of Japan, Europe and the United States. In developed countries, it brings a heavy medical economic burden to patients, their families and society. Statistics show that ischemic cerebrovascular disease is more common. Ischemic cerebro...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K47/42A61K47/34A61P9/10
Inventor 韩峰黄继云卢应梅廖美华杜永忠陶蓉蓉陆楠楠王晓良王欢
Owner ZHEJIANG UNIV
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