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Melittin liposome nanometer preparation, and preparation method and applications thereof

A nano-preparation, melittin technology, applied in the direction of liposome delivery, anti-inflammatory agents, anti-fungal agents, etc., can solve the problems of toxicity, low bioavailability, etc.

Active Publication Date: 2019-02-01
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] At present, there are still many problems in the development and clinical treatment of melittin in diseases such as inflammation, tumor and bacterial and viral infection, such as: the special α-helical structure of melittin itself makes it have a strong bond with phospholipid membranes. Affinity, it is very easy to insert into the lipid bilayer membrane and form holes on the cell membrane, so the free melittin has a strong hemolytic effect and tissue toxicity, and this hemolytic side effect and tissue toxicity are one of the most important obstacles to its clinical application ; In addition, as a polypeptide drug, melittin is easily degraded and metabolized in the circulatory system or tissues after administration, or is adsorbed and bound by other proteins or molecules due to the charge, resulting in low bioavailability and potential toxicity

Method used

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  • Melittin liposome nanometer preparation, and preparation method and applications thereof
  • Melittin liposome nanometer preparation, and preparation method and applications thereof
  • Melittin liposome nanometer preparation, and preparation method and applications thereof

Examples

Experimental program
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Embodiment 1

[0144] Preparation and characterization of embodiment 1 melittin-polyglutamic acid liposome nano-preparation

[0145] Preparation:

[0146] (1) Dissolve melittin and polyglutamic acid (PGA50-100KD, 500KD, 700KD) of different molecular weights in deionized water, so that the final concentration of the aqueous solution is 0.5mg / mL; add melittin solution to polygu Amino acid solution, vortexed for 10s, and incubated at room temperature for 30min to obtain melittin-polyglutamic acid nanoparticles with a mass ratio of melittin to polyglutamic acid of 2:1; using a 100KD ultrafiltration tube, Free melittin was removed by filtration, and the nanoparticles were redispersed in deionized water.

[0147] (2) DOTAP and DOPE lipids were dissolved in chloroform, and liposomes were prepared by film dispersion method, and 1 mg / mL blank cationic liposomes were obtained after hydration with deionized water. In the vortex state, according to the mass ratio of blank liposomes and melittin-polygl...

Embodiment 2

[0153] Embodiment 2 melittin-polyglutamic acid liposome nano preparation stability research

[0154] Preparation:

[0155] The melittin-polyglutamic acid (700KD) nanoparticles prepared in Example 1 were redispersed in deionized water and 4-hydroxyethylpiperazineethanesulfonic acid buffer (HEPES), prepared in Example 1 Good melittin-polyglutamic acid liposome nano-preparations were re-dispersed in deionized water, 4-hydroxyethylpiperazineethanesulfonic acid buffer solution (HEPES), 5% glucose injection and normal saline respectively. At different time points, the particle size, particle size polydispersity index (PDI) and zeta potential were measured using a dynamic light scattering nanometer particle size analyzer (DLS) to investigate its stability. After dialysis, HPLC was used to detect melittin in the dialysate to analyze the melittin leakage of the melittin-polyglutamic acid liposome nano-preparation.

[0156] Among them, such as Figure 5A , the particle size of melitt...

Embodiment 3

[0158] The hemolytic detection of embodiment 3 melittin-polyglutamic acid liposome nano-preparation

[0159]Blood was taken from the eyes of the mice and anticoagulated with sodium heparin. After counting using a hemocytometer, the blood was divided into EP tubes so that each tube contained 5x10^6 blood cells; 2000rpm, centrifuged for 5min to remove the supernatant, and an equal volume of normal saline was added. The melittin-polyglutamic acid nanoparticles obtained in Example 1 and the melittin-polyglutamic acid liposome nano-preparation and free melittin medicine are dispersed in HEPES to obtain different concentrations (by contained melittin amount ) solution and added to the EP tube, incubated at 37°C for 6 hours.

[0160] Afterwards, centrifuge again, collect the supernatant and put it into a 96-well plate, and set up three groups of parallel samples; use a microplate reader for detection, and the detection wavelength is 525nm.

[0161] Hemolysis rate (%) = [(As-Ab) / (Ac-...

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Abstract

The invention belongs to the technical field of novel nanometer medicinal preparation, and more specifically relates to a melittin liposome nanometer preparation, and a preparation method and applications thereof. The melittin liposome nanometer preparation contains melittin liposome which at least contains melittin, an anionic polymer, and a cationic lipid carrier. The raw materials are safe, andare easily available; the preparation method is simple in operation, and is high in repeatability; the particle size and uniformity of the liposome preparation are ideal, drug loading amount is large, preparation stability is excellent, storage is convenient, melittin leakage amount is low, no hemolysis is caused, the toxicity is low, biodegradable characteristic is achieved, functionalization modification can be realized, long circulation in a circulation system and tumor active and passive targeting distribution function are achieved, and large scale production can be realized.

Description

technical field [0001] The invention belongs to the technical field of novel nano-pharmaceutical preparations, and in particular relates to a melittin liposome nano-preparation and its preparation method and application. Background technique [0002] Melittin is the main active substance in bee venom (Vonem), accounting for about 40% of the dry weight of bee venom. It is a polypeptide molecule (NH2-GIGAVLKVLTTGLPALISWIKRKRQQ-CONH2) composed of 26 amino acids. The molecular weight of melittin is 2846Dal, amphiphilic, easily soluble in water, has 6 positive charges under physiological conditions. There are two α-helical structures in the secondary structure of the melittin monomer, which are connected by a hinge structure in the middle, and the C-terminus is a positively charged region. There are two forms of melittin in water, the free structure of the monomer at low concentration and low ionic strength, and the tetrameric form at high concentration and high ionic strength. ...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K47/34A61K47/36A61K47/42A61K38/17A61P35/00A61P31/04A61P31/10A61P29/00
CPCA61K9/1272A61K38/1767A61K47/34A61K47/36A61K47/42A61P29/00A61P31/04A61P31/10A61P35/00
Inventor 彭金良叶然徐宇虹
Owner SHANGHAI JIAO TONG UNIV
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