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Vesicle nano-drug loaded with chloroquine compound as well as preparation method and application of vesicle nano-drug

A technology of nano-drugs and compounds, applied in the direction of nano-drugs, drug combinations, nanotechnology, etc., can solve problems such as inability to achieve effective treatment, cumbersome production process, and low bioavailability of antibody drugs

Active Publication Date: 2021-11-23
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, antibody drugs have the disadvantages of low bioavailability, cumbersome production process, and high price (P. R. Stocco Romanelli, Biologics for rheumatoid arthritis: an overview of Cochrane reviews, SaoPaulo Medical Journal, 2010, 128, 309-357)
[0003] The prior art uses nanocarriers such as liposomes, lipid nanoparticles, PLGA, and silver nanoparticles to load anti-inflammatory drugs such as dexamethasone, prednisolone, p-coumaric acid, MTX, or siTNF-α for treatment RA has achieved certain results; however, there are still the following problems: poor stability, early release of the drug leads to systemic toxicity; the effective concentration of the drug at the inflammatory site is low, and effective treatment cannot be achieved

Method used

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  • Vesicle nano-drug loaded with chloroquine compound as well as preparation method and application of vesicle nano-drug
  • Vesicle nano-drug loaded with chloroquine compound as well as preparation method and application of vesicle nano-drug
  • Vesicle nano-drug loaded with chloroquine compound as well as preparation method and application of vesicle nano-drug

Examples

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preparation example

[0035] The polymer disclosed in the present invention is the prior art, and its preparation and characterization can refer to the applicant’s published literature or patent application, such as CN2016105581166, Y. Fang, W. Yang, L. Cheng, F. Meng, J. Zhang, Z. Zhong, EGFR-targeted multifunctional polymersomal doxorubicinduces selective and potent suppression of orthotopic human liver cancer invivo, Acta Biomaterialia, 2017, 64, 323-333. Take the preparation of PEG-P(TMC-DTC) (5k-15k-2k) and NHS-PEG-P(TMC-DTC) (6.5k-15k-2k) used in the examples as an example to briefly explain.

[0036] Under nitrogen atmosphere, weigh MeO-PEG-OH ( M n = 5.0 kg / mol, 0.009 mmol), TMC (1.93 mmol) and DTC (0.21 mmol) were dissolved in dichloromethane (DCM, 6.8 mL), and the catalyst diphenyl phosphate (DPP, DPP / OH molar ratio was 10 / 1). The airtight reactor was sealed and placed under magnetic stirring in an oil bath at 40 °C for 24 hours. After terminating the reaction with glacial acetic aci...

Embodiment 1

[0047] The preparation and characterization of the vesicle of the chloroquine compound of embodiment one mannose modification

[0048] Preparation and characterization of mannose-modified hydroxychloroquine-loaded vesicles (Man-PS-HCQ)

[0049] Hydroxychloroquine was loaded into vesicles by the pH gradient method. The two polymers Man-PEG-P (TMC-DTC) and PEG-P (TMC-DTC) were dissolved in DMF respectively, then mixed at a molar ratio of 10 / 90, and added to 150 nM citric acid-sodium citrate (pH=3.0) buffer solution, stirred for 3 minutes to form vesicles, and after standing at room temperature for 1 hour, NaOH aqueous solution was added to adjust the pH to 8.5 to establish a pH gradient inside and outside the vesicles. Then add a certain amount of HCQ aqueous solution, place in a shaker (37oC, 100 rpm) overnight, and then dialyze with secondary water for 8 hours, changing the medium every hour to obtain drug-loaded vesicles 10Man-PS-HCQ.

[0050] According to the above method,...

Embodiment 2

[0059] Example 2 In vitro drug release of Man-PS-HCQ.

[0060] Add 1 mL of Man-PS-HCQ (concentration: 1.3 mg / mL, HCQ drug loading: 12.5wt.%) into the dialysis bag (MWCO12000 Da), submerged in 20 mL of secondary water with pH 7.4 and simulated cytoplasm In an aqueous solution in an internal reducing environment (pH 7.4, 10 mMGSH), placed in a 37-degree air shaker (200 rpm), at the set time points (0.25, 0.5, 1, 2, 4, 6, 8, 12, 24 hour) remove 5 mL of dialysate, and then add 5 mL of corresponding fresh dialysate. The concentration of HCQ in the medium taken out was tested by HPLC and the cumulative release amount was calculated (n=3, the experimental results were averaged). The cumulative release amount can be calculated by the following formula:

[0061]

[0062] In the formula: E r is the cumulative release of HCQ, %; Ve: the replacement volume of the medium, 5 mL; V 0 : the total volume of the medium, 20mL; Ci: the concentration of HCQ in the medium at the i-th samplin...

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Abstract

The invention discloses a vesicle nano-drug loaded with a chloroquine compound as well as a preparation method and application of the vesicle nano-drug. The vesicle nano-drug loaded with the chloroquine compound is prepared by taking a polymer and a chloroquine compound as raw materials, wherein the polymer comprises a hydrophilic chain segment and a hydrophobic chain segment; a side chain of the hydrophobic chain segment is dithiolane containing a disulfide bond. According to the vesicle nano-drug loaded with the chloroquine compound disclosed by the invention, a safe and efficient macrophage-targeted nano-drug is researched and developed for treating rheumatoid arthritis; polymer vesicles are designed for efficiently loading, carrying out targeted delivery and controlling to release drug hydroxychloroquine or chloroquine, so that the enrichment of the drug in cytoplasm is improved; M1M is re-polarized to M2M, so that secretion of proinflammatory cytokines is reduced and secretion of anti-inflammatory cytokines is increased; and the drug can be used for inhibiting DC activation and also can be used for removing ROS and enriching in inflammatory joints. In-vitro and in-vivo experiment results prove that the vesicle nano-drug loaded with the chloroquine compound can be used for carrying out targeted treatment on the rheumatoid arthritis.

Description

technical field [0001] The invention belongs to nano-medicine technology, in particular to vesicle nano-medicine loaded with chloroquine compound and its preparation method and application. Background technique [0002] Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint pain, cartilage damage, and bone loss (D. L. Scott, F. Wolfe, T. W. J. Huizinga, Rheumatoid arthritis, The Lancet, 2010, 376, 1094 -1108). At present, the etiology of RA is still unclear, and there is no radical cure, and it is necessary to take medicine for life. The existing clinical therapies mostly use the combination of non-steroidal drugs, glucocorticoids, antirheumatic drugs (DMARDs) and biological agents. For example, low-dose MTX has been the most commonly used clinical therapy to control the progress of RA since 1980. It is often used as the first choice, but the effective concentration of MTX in the inflammatory site is low, and the systemic toxicity is high (M. TR, ...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K47/34A61K47/26A61K9/19A61K31/4706A61P29/00A61P19/02A61P19/08A61P37/02A61P19/04B82Y5/00B82Y40/00
CPCA61K9/1273A61K47/34A61K47/26A61K9/19A61K31/4706A61P29/00A61P19/02A61P19/08A61P37/02A61P19/04B82Y5/00B82Y40/00Y02A50/30
Inventor 孟凤华方航航杨靓江晶晶沙勇杰钟志远
Owner SUZHOU UNIV
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