Size-variable intelligent drug-loading nano-cluster system and preparation method and application thereof

A drug-loaded nanometer and size technology, which is applied in the direction of pharmaceutical formulations, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., can solve the problems of single function of nano preparations, difficulty in overcoming biological barriers, and large toxic and side effects , to achieve the effect of flexible function expansion, prolonging blood circulation time, and efficient accumulation

Active Publication Date: 2021-05-28
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

It can effectively solve the problems of poor targeting, high toxicity and side effects of existing anti-tumor drugs, single function of existing nano-preparations, and difficulty in overcoming many continuous biological barriers in the body.

Method used

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  • Size-variable intelligent drug-loading nano-cluster system and preparation method and application thereof
  • Size-variable intelligent drug-loading nano-cluster system and preparation method and application thereof
  • Size-variable intelligent drug-loading nano-cluster system and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0058] Example 1: Preparation and characterization of drug-loaded nanocluster PADNc@DOX, such as figure 1 , figure 2 shown

[0059] 1.1 Preparation of small-sized drug-loaded micelles AmDM / DOX

[0060] The AmDM used in the following examples is AmD1, and the preparation method is described in "Wei, T.; Chen, C.; Liu, J.; Liu, C.; Posocco, P.; Liu, X.; Cheng, Q.; Huo Liang, Z.; Fermeglia, M.; Pricl, S.; Liang, X.-J.; Rocchi, P.; Peng, L. Anticancer Drug Nanocelles Formed by Self-Assembling Amphiphilic Dendrimer to Combat Cancer Drug Resistance .Proc.Natl.Acad.Sci.U.S.A.2015,112,2978–2983, DOI: 10.1073 / pnas.1418494112” has detailed records. DOX represents the corresponding doxorubicin.

[0061] The thin-film dispersion method is used to prepare small-sized nanoparticles loaded with hydrophobic drugs. The specific preparation method is as follows:

[0062] (1) Dissolve doxorubicin hydrochloride in a mixed solvent (chloroform:methanol=1:1, v / v). Add triethylamine (the molar...

Embodiment 2

[0075] Example 2: Responsive analysis of drug-loaded nanocluster PADNc@DOX

[0076] 2.1 Acid sensitivity experiment

[0077] (1) The pH of the drug-loaded nanocluster solution was adjusted to 6.5, incubated in a constant temperature shaker at 37°C, and the particle size change was monitored by a laser particle size analyzer. Such as Figure 4 As shown, the rapid decrease in the slightly acidic condition indicated that the outer network PPCD would be broken under the condition of simulating the slightly acidic tumor, proving that the nanoclusters could successfully respond to the slightly acidic environment of the tumor to release the small-sized drug-loaded nanoparticles.

[0078] (2) Adjust the pH of the drug-loaded nanocluster solution to 6.5, incubate in a constant temperature shaker at 37°C, and observe its self-assembled morphology with a transmission electron microscope. The TEM image shows that the acid-sensitive bond between PPCD and drug-loaded nanomicelles is broke...

Embodiment 3

[0082] Example 3: Drug release analysis of drug-loaded nanocluster PADNc@DOX

[0083] A multifunctional microplate reader (BioTek) was used to measure the drug release at different times and in different environments. Add a certain amount of drug (PADNc@DOX) into the dialysis bag (MWCO=10000Da), place it in a centrifuge tube containing solutions of different pH (pH7.4, pH 5.0), and place it in a constant temperature shaker Incubation. The dialyzed fluid was taken at different time points from 0 to 48 hours, and the same amount of PBS was added to measure the concentration of the dialyzed fluid at different time points. Such as Figure 5 As shown, the release kinetics curve indicated that the introduction of the outer network protective layer PPCD can increase the stability of the nano-preparation under physiological conditions and prevent drug leakage. In an acidic environment, the drug can achieve rapid release, 60% can be released within 48 hours, which is much higher tha...

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Abstract

The invention discloses a size-variable intelligent drug-loading nano-cluster system and a preparation method and application thereof. The drug-loaded nano-cluster is composed of an outer-layer reticular host carrier with good biocompatibility and an inner small-size parasitic carrier. The nano-cluster has good safety and long circulation characteristics, after being efficiently accumulated at a tumor part, the nano-cluster intelligently adjusts the size under the stimulation of a tumor microenvironment, and releases small-size drug-loaded micelles to penetrate through a compact tumor matrix to realize deep drug delivery, so that the permeability and lethality of the drug are enhanced, and the toxic and side effects are reduced. The nano-cluster is a flexible drug loading platform, and has great practical value in the field of nano-drug treatment of solid tumors.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to a size-variable intelligent drug-loading nano-cluster system and its preparation method and application. Background technique [0002] Chemotherapy plays a very important role in anticancer treatment, but the toxicity and side effects caused by poor selectivity are still common problems of small molecule chemotherapeutic drugs commonly used in clinic. The discovery of the EPR effect (high permeability and retention effect of solid tumors) has led to the rapid development of nano-drug delivery systems, but its clinical and industrial transformation rates are low, which is closely related to the complex metabolic process of nano-drugs in the body: nano-drugs in After drug administration, at least five processes of blood circulation, tumor aggregation, tumor infiltration, cell internalization, and drug release will be experienced, and the efficiency of each ste...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/64A61K47/60A61K47/69A61K9/127A61K47/34A61K31/704A61P35/00
CPCA61K47/64A61K47/60A61K47/6935A61K9/1277A61K47/34A61K31/704A61P35/00
Inventor 刘潇璇韩丽丽陈朋李运朱丹丹
Owner CHINA PHARM UNIV
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