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Intravenous injection drug-loading targeting nano-carrier for RA (Rheumatoid Arthritis) and preparation method of drug-loading targeting nano-carrier

A nano-carrier, targeting technology, applied in non-active ingredients medical preparations, medical preparations containing active ingredients, pharmaceutical formulas, etc.

Active Publication Date: 2021-09-10
福州市第一医院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there is no existing technology to realize the targeting of NK4 to FLSs, and there is no mature solution that can be used for reference in terms of carrier selection and conjugation methods. Moreover, in the process of drug delivery, what impact does the environmental condition have on the conjugate? , how to control drug release and other aspects are still in the blank

Method used

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  • Intravenous injection drug-loading targeting nano-carrier for RA (Rheumatoid Arthritis) and preparation method of drug-loading targeting nano-carrier
  • Intravenous injection drug-loading targeting nano-carrier for RA (Rheumatoid Arthritis) and preparation method of drug-loading targeting nano-carrier
  • Intravenous injection drug-loading targeting nano-carrier for RA (Rheumatoid Arthritis) and preparation method of drug-loading targeting nano-carrier

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Embodiment 1 (synthesis and characterization of PCADK)

[0024] 1. Materials and methods

[0025] 1.1 Experimental reagents and instruments

[0026] 1,4-cyclohexanedimethanol (Aladdin C105684); redistilled benzene (Aladdin B116191); p-toluenesulfonic acid (McLean T823839); 2,2-dimethoxypropane (Aladdin D105750); Ethylamine (McLean T818772); n-Hexane (McLean H811141).

[0027] Constant temperature magnetic stirring (Dalong); X-ray diffractometer (Rigaku, Japan); Fourier transform infrared spectrometer (Shimadzu IR Prestige-21, Japan); Nuclear magnetic resonance (BRUKER DMX300, Switzerland).

[0028] 1.2 PCADK material preparation

[0029] Connect the 3-neck flask and the spherical condenser in the fume hood, and use a heatable magnetic stirring water bath to heat the experiment. Accurately weigh 12.5031g of 1,4-cyclohexanedimethanol in a three-necked flask, connect the water separator and the condensing reflux tube, add 30ml double-distilled benzene, heat to 87°C on ...

Embodiment 2

[0047] Embodiment 2 (preparation and characterization of PCADK composite nanomaterial)

[0048] 1. Materials and methods

[0049] 1.1 Experimental cells

[0050] MH7A cells, HTX1833, Shanghai Tong Biotech.

[0051] 1.2 Experimental reagents and instruments

[0052] High-glucose complete DMEM (KGM31800S-500, KGI Bio); trypsin-EDTA digestion solution (T1300, Solarbio); PBS (02-024-1ACS BI); Trizon Reagent (CW0580S, CWBIO); Ultrapure RNA ultrapure RNA extraction Kit (CW0581M, CWBIO); HiScript II Q RT SuperMix for qPCR (+gDNA wiper) (R223-01, Vazyme); 2×SYBR Green PCR Master Mix (A4004M, Lifeint); RIPA cell lysate (C1053, Beijing Pulilai); BCA protein quantification kit (CW0014S, Kangwei Century); egg yolk lecithin (L8260, Suo Laibao); vasoactive intestinal peptide ([D-p-Cl-Phe6,Leu17]-VIP) (HY-P1159, MCE); Sodium hyaluronate (S8190 Solebol); Polyvinyl alcohol (PVA), polyethyleneimine (PEI) Aladdin reagent; PCADK material (prepared in the previous experiment); CO 2 Incubator ...

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Abstract

The invention provides an intravenous injection drug-loading targeting nano-carrier for RA (Rheumatoid Arthritis) and a preparation method of the drug-loading targeting nano-carrier. According to the technical scheme, for final effector cells FLSs of RA, PCADK with a pH controlled release function is used as a main skeleton; PEI is added to modify and wrap NK4 to improve nucleic acid stability; then, VIP is added to carry out active targeting regulation and control; a novel multifunctional drug-loading targeting nano-carrier for intravenous injection is constructed step by step; acid sensitive release is responded; therefore, the FLSs can be efficiently delivered to the RA focus; and the optimal anti-RA curative effects of extracellular inhibition of angiogenesis, intracellular killing of malignant hyperplasia FLSs and remodeling of the immune microenvironment of the RA focus are achieved. According to the invention, the PCADK composite nanomaterial is prepared based on an emulsion method; and experimental results show that: the particle size of the obtained PCADK composite nanomaterial is at the nanometer level, the Zeta potential is particles with positive electricity, the morphology is good, and the PCADK composite nanomaterial is expected to serve as a brand new targeted drug to be used for clinical treatment of RA.

Description

technical field [0001] The invention relates to the technical field of targeted drugs, in particular to a drug-loaded targeting nanocarrier for intravenous injection for RA and a preparation method thereof. Background technique [0002] At present, the treatment of rheumatoid arthritis (RA) at home and abroad is mainly based on immunosuppression and inhibition of inflammatory factors, and it is difficult to completely improve the curative effect of RA. The inventors previously discovered that NK4 has a strong killing effect on FLSs of RA patients, but there are problems such as safety and sustainability of gene therapy. In this case, how to realize the targeting of NK4 to FLSs is the key to whether it can be applied to the clinical treatment of RA. [0003] In the design of targeted drugs, it is necessary to first select a carrier that targets the target efficiently, and at the same time ensure that the carrier can be effectively coupled with the drug. On this basis, the in...

Claims

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Application Information

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IPC IPC(8): A61K9/14A61K38/17A61K47/34A61K47/42A61K47/58A61P19/02A61P37/02C08G65/34
CPCA61K9/0019A61P19/02A61P37/02A61K47/58A61K9/146A61K47/34A61K38/1709A61K47/42C08G65/34Y02A50/30
Inventor 阙文忠
Owner 福州市第一医院
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