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Biomimetic multifunctional lipoprotein nanoparticle modified by biological peptide and preparation method and application thereof

A lipoprotein and biological peptide technology, applied in the field of biomimetic multifunctional lipoprotein nanoparticles and their preparation, can solve the problems of difficult to determine the specific process of complex diseases, difficult to achieve disease treatment effects, no clear reports, etc. and drug targeting, improving bioavailability, and avoiding biosafety issues

Active Publication Date: 2021-07-20
NANJING UNIVERSITY OF TRADITIONAL CHINESE MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to problems such as large toxic side effects and easy drug resistance, it is difficult for a single chemotherapeutic drug to achieve a good therapeutic effect on the disease, and it is also difficult to determine the specific process of complex diseases. Therefore, people began to combine chemotherapeutic drugs with photosensitizers and The combination of imaging agents and entrapped in nanocarriers can realize the precise targeting and deep penetration of the lesion. The introduction of photosensitizers can expand the treatment mode and realize the combination of chemotherapy and phototherapy. Disease progression, showing the exact location, shape, and size of the tumor
Although there have been some reports on the combination of traditional Chinese medicine monomers and contrast agents, there are still quite a few gaps to be filled in the application of diffuse tumors and how to achieve efficient and targeted delivery.
In addition, how to efficiently entrap drugs into hydrophobic carriers in the form of nanometers and make full use of the internal hydrophobic drug-loading space of biomimetic apolipoprotein nanoparticles has not yet been clearly reported.

Method used

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  • Biomimetic multifunctional lipoprotein nanoparticle modified by biological peptide and preparation method and application thereof
  • Biomimetic multifunctional lipoprotein nanoparticle modified by biological peptide and preparation method and application thereof
  • Biomimetic multifunctional lipoprotein nanoparticle modified by biological peptide and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Example 1: Preparation of MnAs co-precipitated core and hydrophobic modification

[0052] Take 7.5mL of cyclohexane, 1.5mL of triton, and 1mL of n-hexanol, and mix with magnetic stirring for 10min to form a transparent and stable reverse microemulsion system. Weigh an appropriate amount of manganese chloride tetrahydrate, add 1 mL of ultrapure water, and vortex to dissolve to prepare a manganese chloride solution. Weigh an appropriate amount of ATO, add 1mL of 1M NaOH solution, vortex to dissolve, add concentrated hydrochloric acid, adjust the pH to 7.4, and prepare an ATO solution. 100 μL of manganese chloride solution was added dropwise to the inverse microemulsion system, and magnetically stirred for 15 min. 100 μL of ATO solution with the same molar concentration was added dropwise, and magnetically stirred for 2 hours to form a pale yellow MnAs co-precipitation.

[0053] 100 μL of 20 mmol / L 1,2-oleoylphosphatidic acid sodium salt (DOPA) chloroform solution was ad...

Embodiment 2

[0054] Example 2: Preparation process of carrying MnAs and modifying functional peptide Mel biomimetic lipoprotein nanoparticles (Mel-LNPs / MnAs)

[0055] Weigh 1.5 mg of DMPC, add 0.5 mL of MnAs co-precipitation solution prepared under "Example 1" to dissolve, add dropwise to D4F solution (0.75 mg, 1.5 mL) and stir for 2 h, then add α-Mel solution (0.5 mg, 0.5mL) was stirred and emulsified for 2h. Sonicate (195W) for 10 min, and remove the organic solvent by rotary evaporation. Pass through a 0.8 μm filter membrane, centrifuge ultrafiltration (5000r / min, 10min) with a 30k Da ultrafiltration tube to remove free drug, and resuspend in PBS buffer to obtain Mel-LNPs / MnAs.

[0056]The mass ratio of D4F polypeptide to phospholipid was selected as 0.5:1, and the amount of phospholipid (DMPC / PC) and phospholipid used in the preparation of Mel-LNPs / MnAs was further investigated. After dilution with water, the particle size, polydispersity index (PDI) and Zeta potential of the prepara...

Embodiment 3

[0065] Example 3: Investigation on the Properties of Biomimetic Multifunctional Lipoprotein Nanoparticles Modified by Biological Peptides

[0066] The optimal prescription was selected for the preparation of Mel-LNPs / MnAs, and the following investigations were carried out.

[0067] 1.1 Morphology of Mel-LNPs / MnAs

[0068] Observation with a high-resolution transmission electron microscope showed that figure 2 As shown in A, it can be seen that the shape of the Mel-LNPs / MnAs particles is regular and spherical, and the phenomenon of adhesion and aggregation between the particles is less. After zooming in, it can be seen that there are a certain number of black lattices distributed in the middle of the particles, indicating that the MnAs co-precipitation is better loaded in the LNPs.

[0069] Under the same field of view, the two elements of Mn and As were scanned, and the energy spectrum point scanning test was carried out. The results are as follows figure 2 As shown in B,...

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Abstract

The invention discloses a biomimetic multifunctional lipoprotein nanoparticle modified by biological peptide and a preparation method and application thereof, the multifunctional biomimetic lipoprotein nanoparticle is composed of a biomimetic lipoprotein nano-carrier shell modified by biological peptide and a nano-form drug core, and the carrier shell is composed of apolipoprotein bionic peptide, biological peptide and natural phospholipid substitute. The preparation method comprises a film dispersion method and an emulsification evaporation method. The preparation method disclosed by the invention is simple and mild in condition and low in cost, and the prepared biological peptide modified biomimetic multifunctional lipoprotein nanoparticle has the advantages of high drug loading capacity, high biomimetic property, strong penetrability, biological safety, lesion site targeting property, drug loading mode diversity and the like. A nano-drug delivery platform can realize 'diagnosis and treatment integration' and 'multi-mode combined treatment', and can realize timely diagnosis and efficient treatment of complex progressive diseases such as tumors, neurodegenerative diseases and the like.

Description

technical field [0001] The invention belongs to the technical field of nano preparations, and in particular relates to biomimetic multifunctional lipoprotein nanoparticles modified by biological peptides and a preparation method and application method thereof. Background technique [0002] Lipoproteins are a class of spherical particles composed of a hydrophobic inner core rich in sterol lipids and triglycerides and an outer shell composed of apolipoproteins, phospholipids, cholesterol, etc., and play an important role in the lipid transport process in vivo. According to different densities, lipoproteins can be divided into four categories, including chylomicrons (Chylomicrons, CM), very low-density lipoprotein (VLDL), low-density lipoprotein (Low-density lipoprotein, LDL) and high-density lipoprotein Lipoprotein (High-density lipoprotein, HDL). Apolipoprotein is an important component of lipoprotein, mainly including A, B, C, D, E five classes. Apolipoprotein A family (Ap...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K41/00A61K45/00A61K47/54A61K47/62A61K49/00A61K49/18A61P25/00A61P35/00
CPCA61K47/6929A61K47/62A61K47/544A61K41/0057A61K45/00A61P25/00A61P35/00A61K49/0093A61K49/1866A61K2300/00
Inventor 王若宁黄剑宇张新茹狄留庆
Owner NANJING UNIVERSITY OF TRADITIONAL CHINESE MEDICINE
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