Polymer nanoparticles carrying water-soluble small peptide and modified by wheat germ agglutinin and preparation method thereof

Abstract

The invention relates to polymer nanoparticles carrying water-soluble small peptide and modified by wheat germ agglutinin and a preparation method thereof. The average particle size of the nanoparticles is 140nm, the encapsulation efficiency reaches 50%, and the drug loading capacity is 11%. The preparation method comprises the following steps: (1) dissolving NR2B9c in water to obtain an internal water phase; (2) dissolving a polymeric material in dichloromethane to obtain an oil phase; (3) adding the internal water phase into the oil phase and performing ultrasonic treatment to obtain W / O primary emulsion; (4) adding the W / O primary emulsion into an emulsifier-containing external water phase and performing ultrasonic treatment to obtain W / O / W compound emulsion; and (5) diffusing the W / O / W compound emulsion in a diffusive-phase solution, adding sulfhydrylated WGA, stirring at a low speed for incubation, removing the organic solvent, freezing and centrifuging to obtain NR2B9c-entraped WGA modified polymer nanoparticles, wherein perfect brain targeting is realized through intranasal administration.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to wheat germ agglutinin (wheatgermagglutinin, WGA)-modified polymer nanoparticles loaded with water-soluble small peptides for nasal administration, and a preparation method and application thereof. The water-soluble small peptides It is NR2B9c with a relative molecular weight of 977Da. Background technique [0002] Stroke is a common and frequently-occurring disease that endangers human health. It has the characteristics of high morbidity, disability, mortality and recurrence. Stroke is mainly divided into two categories: ischemic stroke and hemorrhagic stroke, among which ischemic stroke is the most common type, accounting for about 80% of all strokes. However, clinically, apart from early use of thrombolytic drugs that are effective for ischemic stroke, there is still a lack of therapeutic drugs with clear curative effects. Therefore, it is of great signi...

AI Technical Summary

Problems solved by technology

Tat can transport the peptides or proteins connected to it across the membrane into various tissues and cells. Although NR2B9c carried by Tat can effectively pass through the blood-brain barrier, there are still the following disadvantages: ①Tat carrying NR2B9c can enter various tissues of the human body and cells, in vivo distribution is non-selective

② There are still many issues to be considered in the application of fusion proteins in the treatment of human diseases, especially the safety is not yet clear

③The time window of stroke treatment is very critical, the sooner the treatment is received, the better the effect, and Tat-NR2B9c is designed for intravenous injection, which must be operated by professional medical staff, which is inconvenient to use

However, the residence time in the nasal cavity is short, and it lacks the selectivity to the mucous membrane of the olfactory area, the main absorption site, and the ability to enter the brain is still limited.

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