A physically encapsulated tumor-targeted nano-drug delivery system and its preparation method and application

A nano-drug delivery system and tumor-targeting technology, applied in the field of pharmaceutical preparations, to achieve the effects of enhancing in vitro growth inhibition, good targeting, and improving drug release characteristics

Active Publication Date: 2020-05-12
EAST CHINA NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Neuropilin-1 (NRP-1) is a type I transmembrane glycoprotein on the cell surface, and NRP-1 is expressed in many human tumor tissues, including prostate cancer, breast cancer, melanoma, pancreatic cancer and glioma , but not expressed in the corresponding normal tissue epithelial cells

Method used

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  • A physically encapsulated tumor-targeted nano-drug delivery system and its preparation method and application
  • A physically encapsulated tumor-targeted nano-drug delivery system and its preparation method and application
  • A physically encapsulated tumor-targeted nano-drug delivery system and its preparation method and application

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Experimental program
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Effect test

Embodiment 1

[0040] Characterization of the polypeptide C-RGERPPR

[0041] The purchased pure peptide was characterized by HPLC and LC-MS methods.

[0042]The analytical HPLC chromatographic method is as follows, chromatographic column: Diamonsil C18 (5μm, 200×4.6mm); mobile phase A: 0.1% TFA water, mobile phase B: 0.1% TFA acetonitrile; elution program: 0 ~ 2min: 5% B , 2~32min: 5%~65%B, 32~33min: 65%~90%B, 33~36min: 90%B;, 36~37min: 90%~5%B, 37~45min: 5%B ; Flow rate: 0.7mL / min; Column temperature: 40°C; Wavelength: UV 214, 280nm. figure 2 Indicates that its purity is greater than 98%; image 3 It shows that the molecular weight of the polypeptide is 970.4, and the mass MS spectrum shows that its molecular weight is consistent with the theory.

Embodiment 2

[0044] Synthesis and Characterization of DSPE-PEG-RGERPPR

[0045] Get C-RGERPPR pure product 25mg to be dissolved in the 2ml PBS (Ph7.0-7.4, 1xPBS) solution of Ph7.0-7.4, take maleimide-polyethylene glycol-phospholipid complex DSPE-PEG-Mal ( The molar equivalent is 0.8 times of RGERPPR) dissolved in 0.5ml DMF, added to the polypeptide aqueous solution, ultrasonically removed bubbles, stirred for about 1 hour, the DSPE-PEG-Mal reaction was complete, dialysis (molecular weight cut-off 3500Da, dialysis medium is water) to remove excess C-RGERPPR and DMF, lyophilized to give RGERPPR-PEG-DSPE, H1-NMR. H1-NMR spectrum shows, Figure 4 . It is the nuclear magnetic spectrum of RGERPPR-PEG-DSPE and maleimide-polyethylene glycol-phospholipid complex (Mal-PEG-DSPE). The NMR spectrum of RGERPPR-PEG-DSPE disappeared at 6.7ppm, that is, the characteristic peak of maleimide, indicating that the synthesis of RGERPPR-PEG-DSPE was successful.

Embodiment 3

[0047] Preparation and characterization of nano drug delivery system modified by physical encapsulation of RGERPPR-PEG-DSPE to PGG-PTX

[0048] Weigh a, PGG-PTX and b, RGERPPR-PEG-DSPE respectively, the molar ratio a:b=98:2. Dissolve PGG-PTX with 0.5% sodium cholate solution, and dissolve RGERPPR-PEG-DSPE with a mixed solution of dichloromethane:acetone=3:1. Add solution b to solution a, and vortex while adding dropwise. In the ice bath, the cell ultrasonic breaker ultrasonicated at 300w, supersonicated for 2s, with an interval of 3s, and ultrasonicated for 2min to obtain the emulsion. 8 ml of 1% sodium cholate solution was added to the emulsion, and magnetically stirred for 10 min. Remove the organic solvent by rotary evaporation in a water bath at 35°C; centrifuge at 21,000 g for 45 minutes at 4°C, discard the supernatant, and resuspend the precipitate with physiological saline to obtain a nanoparticle solution. The sample was separated and purified at a UV detection wave...

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Abstract

The invention discloses a physically encapsulated tumor targeted nano drug delivery system and a preparing method and application. The drug delivery system comprises an RGERPPR polypeptide modified target element, a nano-micelle and an anti-tumor drug. The target element is 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol RGERPPR, the micelle is a polyglutamic acid (PGG) polymeric scaffold and a glutamic acid branched chain on the scaffold, and the anti-tumor drug is paclitaxel (PTX). The tail end of the glutamic acid branched chain of the PGG polymeric scaffold is bonded with the anti-tumor drug PTX through an ester bond to form PGG-PTX, and then 1,2-distearoyl-sn-glycero-3-phosphoethanolamine at the hydrophobic end of the target element is wrapped in PGG-PTX under the hydrophobic interaction between PTX and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine in the target element, so that the targeted anti-tumor nano drug delivery system is formed. The drug delivery system can be used for targeted delivery of tumor treatment drugs, a good treatment effect is realized in brain glioma treatment, and the median survival time of a BALB / C brain glioma nude mouse is prolonged.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to a preparation method and use of nano-micelle drugs for realizing the modification of targeting elements by physical encapsulation. Background technique [0002] Glioma is one of the most common brain tumors, accounting for about 40% of the incidence of brain tumors. Its degree of deterioration and postoperative recurrence rate are high and the invasion speed is fast, resulting in a short survival period of glioma patients: clinically The survival time of patients diagnosed with stage I or stage II is 6-8 years, that of patients with stage III is 3 years, and that of patients with stage IV is generally only 12-18 months. As an intracranial tumor, glioma has many unique features, and its tumor formation and development have complex various barriers, such as enzyme barrier, blood-brain barrier (BBB) ​​and tumor blood-brain barrier (BBTB), which hinder drugs or ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/107A61K47/64A61K47/04A61K31/337A61P35/00
CPCA61K9/1075A61K31/337A61K47/02
Inventor 俞磊孙磊周靖娥彭婷李奇龙南立娟高礼鹏闫志强王镜朱建中
Owner EAST CHINA NORMAL UNIV
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