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Microneedle for treating psoriasis through percutaneous delivery of lipidosome and preparation method of microneedle

A technology of liposome and psoriasis, which is applied in the field of microneedle and its preparation for the transdermal delivery of liposome for the treatment of psoriasis. Road side effects, improve the effect of treatment

Pending Publication Date: 2022-05-06
ZHEJIANG UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] The purpose of the present invention is to solve the defects and side effects of methotrexate MTX, a psoriasis treatment drug commonly used in the prior art, and to solve the problem that microneedles are difficult to penetrate due to scales and thickening on the skin surface of psoriasis, and to provide a A dissolvable flexible-backed microneedle for transdermal delivery of MTX liposomes for the treatment of psoriasis

Method used

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  • Microneedle for treating psoriasis through percutaneous delivery of lipidosome and preparation method of microneedle
  • Microneedle for treating psoriasis through percutaneous delivery of lipidosome and preparation method of microneedle
  • Microneedle for treating psoriasis through percutaneous delivery of lipidosome and preparation method of microneedle

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Experimental program
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Effect test

Embodiment 1

[0049] Embodiment 1: the preparation of MTX liposome

[0050] (1) Prepare liposomes by reverse evaporation method:

[0051] 30 mg of egg yolk lecithin (EPC), 15 mg of cholesterol (Chol) were dissolved in 9 mL of chloroform as an oil phase. Dissolve 6 mg of MTX in 3 mL of PBS with a pH of 6.5, add it to the above oil phase as the water phase, and ultrasonically (power 150 W) with an ice-bath probe for 5 min to form a w / o emulsion. Rotate at 30 °C for 30 min to evaporate the organic solvent to obtain Semi-solid jelly. Continue to add 3 mL of LPBS, and rotate under reduced pressure at 30°C for 5 min to remove residual organic solvent. Finally, in the cell disruptor, the ice-bath probe was ultrasonicated (power 150W) for 5 minutes to obtain a uniform drug-loaded liposome solution.

[0052] (2) MTX liposome lyophilized powder preparation:

[0053] After the liposome solution was dialyzed (3500Da, 48h), the free drug MTX was removed, and the lyoprotectant (trehalose) was added t...

Embodiment 2

[0054] Embodiment 2: Characterization of MTX liposomes

[0055] (1) Measurement of liposome particle size, PDI, zeta potential:

[0056] The particle size, PDI and zeta potential of the liposomes prepared in Example 1 were measured at 25° C. with a DLS particle size analyzer. Add the MTX liposome solution into the particle size cup, and measure in parallel three times. During the test, record the average hydrodynamic diameter and the polydispersity index (PDI), add a potentiometric electrode, make the electrode piece completely immersed in the solution to be tested, measure in parallel three times, record the zeta potential of the liposome during the test, and analyze .

[0057] Precisely draw 1mL of liposomes into a 100mL test tube, add 5mL of demulsifier (chloroform / methanol = 1:1 (V / V)), mix well, and ultrasonicate for 30-40min to make the demulsification uniform, after standing still, take Dilute the upper layer solution, measure its absorbance value at 303nm with a UV ...

Embodiment 3

[0070] Example 3: Preparation of blank soluble microneedles

[0071] The microneedle mold is made of polydimethylsiloxane PDMS, which can be made figure 1 The 6×6 conical MNs shown (the bottom diameter of a single MNs is 130 μm, the tip diameter is 12 μm, and the needle length is 500 μm).

[0072] The soluble microneedle is prepared according to the following steps: weigh methyl vinyl ether-maleic acid PMVE MAH, add purified water to dissolve, and mix well on a four-dimensional rotary mixer to obtain PMVE MAH solution, which is slightly yellow. Place PMVE MAH in a microneedle mold made of polydimethylsiloxane PDMS, centrifuge at 3500rad / min for 30min to form needles; scrape off excess needle material PMVE MAH, and place the mold in a vacuum desiccator at room temperature , after negative pressure drying for 12 hours, the mixed backing material of HPC and WCS was centrifuged for 30 minutes at a reduced speed (horizontally centrifuged for 5 minutes each at 3000, 2500, 2000, 150...

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Abstract

The invention belongs to the field of pharmaceutical preparations, and particularly relates to a microneedle for treating psoriasis through percutaneous delivery of lipidosome and a preparation method of the microneedle. The preparation method comprises the following steps: firstly, preparing a drug-loaded liposome by a reverse evaporation method, preparing the drug-loaded liposome into MTX liposome freeze-dried powder, and then loading the powder into a microneedle cavity. The microneedle is prepared through a two-step method, liposome freeze-dried powder is loaded in a cavity of the soluble microneedle, a drug is transdermally delivered to the skin, and the residence time of the drug at an inflammation part is prolonged. The prepared microneedle is good in mechanical property, can break through the barrier of the cuticle and can be directly attached to the position near the psoriasis lesion, the drug curative effect is improved, and the painless and minimally invasive effect is achieved. According to the method, the percutaneous penetration capacity of the medicine is improved, the toxicity of the medicine is reduced, the biocompatibility is improved, slow medicine release is realized, the medicine effect is fully played, and meanwhile, side effects are reduced.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to a microneedle for transdermally delivering liposomes for treating psoriasis and a preparation method thereof. Background technique [0002] Psoriasis is a T-cell-mediated disease that often manifests in the skin or joints due to faulty processing of signals from the autoimmune system. The histopathology of psoriasis is characterized by epidermal hyperplasia, impaired keratinocyte differentiation, marked inflammatory infiltration, and increased angiogenesis, which seriously affect the quality of life of patients. Therefore, small molecule drugs (methotrexate MTX, cyclosporine A, retinoic acid, etc.) and biologics (etanercept, adalimumab, certolizumab, etc.) are commonly used to treat psoriasis . However, the high price of targeted biologics discourages patients, resulting in low compliance and unsustainable. [0003] Methotrexate (MTX) is still the first-l...

Claims

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Application Information

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IPC IPC(8): A61K9/00A61K31/519A61K47/12A61K47/36A61K47/38A61K9/19A61P17/06
CPCA61K31/519A61K9/0021A61K47/12A61K47/38A61K47/36A61K9/19A61P17/06
Inventor 严琴英方敏杨根生翁嘉绮沈淑琳王燕
Owner ZHEJIANG UNIV OF TECH
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