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Platelet-like liposome drug delivery system, and preparation method and application thereof

A drug delivery system and platelet technology, applied in liposome delivery, pharmaceutical formulations, anti-tumor drugs, etc., can solve the problems of low drug loading, short cycle time, and affecting platelet targeting

Inactive Publication Date: 2020-07-07
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, in the existing studies on the targeted delivery of platelets to tumors, platelet membrane-encapsulated nanoparticles, that is, platelet membrane-coated PLGA nanoparticles and platelet vesicles, both exhibit tumor targeting effects, but there is still time for circulation in vivo. Therefore, constructing a platelet-like liposome drug delivery system with long-term circulation ability in vivo can solve the problem of prolonging the circulation time in vivo while retaining the platelet targeting function. a question
[0005] At the same time, the traditional platelet membrane-coated PLGA nanoparticles still have the defect of low drug loading capacity, and its drug loading capacity is far from meeting the dosage requirements of clinical medication; while platelet-mimicking liposomes have the drug-loading capacity of traditional liposomes. , taking doxorubicin as an example, the drug loading of traditional liposomes can be as high as 90%, while the drug loading of PLGA does not exceed 10%

Method used

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  • Platelet-like liposome drug delivery system, and preparation method and application thereof
  • Platelet-like liposome drug delivery system, and preparation method and application thereof
  • Platelet-like liposome drug delivery system, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0056] Example 1 Preparation of platelet-like liposomes

[0057] 1) Preparation of traditional liposomes: accurately weigh 4mg egg yolk lecithin and 0.4mg DSPE-PEG 2000 Dissolve in 10mL of dichloromethane, remove the dichloromethane by rotary evaporation under reduced pressure at room temperature, form a film, add 1.6mL of distilled water after 30min to hydrate;

[0058] 2) Preparation of platelet-like liposomes: 0.4mL of activated human platelet membrane suspension was added to the hydration solution of 1), mixed with ultrasound for 1 min, and then passed through 800μm, 400μm, 200μm and 100μm polycarbonate membranes, namely Obtain the platelet-like liposome PL of the present invention,

[0059] In addition, the liposome suspension obtained by step 1) was subjected to ultrasonic and extrusion treatment under the same conditions in step 2) to obtain traditional liposome LI, and 1 mL of activated human platelet membrane suspension was subjected to the same conditions in step 2). Ultra...

Embodiment 2

[0061] Example 2 Characterization of platelet-like liposomes

[0062] 1) Observation of the surface morphology of platelet-like liposomes: the LI, PL and PV in Example 1 were diluted to 0.1 mg / mL, stained with 2% phosphotungstic acid, and observed under a transmission electron microscope. The experimental results Such as figure 2 Shown

[0063] 2) Investigation of particle size and potential of platelet-like liposomes: LI, PL, PV and Platelet in Example 1 were diluted to 0.2 mg / mL respectively, and the particle size and surface charge were measured with a dynamic light scattering instrument. The experimental results are as image 3 , Figure 4 Shown

[0064] 3) In vitro stability study of platelet-like liposomes: Place 0.2mg / mL LI, PL and PV at 4°C for a week, and monitor the particle size changes with a dynamic light scattering instrument. The experimental results are as follows Figure 5 Shown.

Embodiment 3

[0065] Example 3 In vitro adhesion experiment of platelet-like liposomes

[0066] 1) In vitro adhesion verification of platelet-like liposomes to collagen: DiD-labeled LI, PL and PV samples were prepared using the method in Example 1, wherein the mass ratio of DiD to phospholipid was 1:1000. A 96-well plate was coated with 2mg / mL human collagen IV and air-dried overnight at 4°C. Then add 100μL of DiD-labeled LI, PL or PV to each well, rinse 3 times with PBS after 5min, then add 100μL of DMSO to dissolve DiD, and quantify the amount of each sample attached to the collagen plate by a microplate reader, where excitation wavelength / emission The wavelength is 643 / 665nm respectively. The experimental results are as Image 6 Shown

[0067] 2) In vitro adhesion verification of platelet-like liposomes to fibrinogen: DiD-labeled LI, PL and PV samples were prepared using the method in Example 1, where the mass ratio of DiD to phospholipid was 1:1000. 96 wells Add 100 μL of 2.0 mg / mL fibrin...

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Abstract

The invention belongs to the technical field of pharmaceutical preparations, and relates to a targeted drug delivery system, specifically to a platelet-like liposome drug delivery system, and a preparation method and an application thereof. The drug delivery system is prepared from a platelet membrane and a traditional liposome through extrusion membrane-filtering and fusing. The drug delivery system has the advantages of both natural targeting of a platelet and in-vivo long circulation of a lipidosome; in-vitro adhesion experiment results prove that the platelet-like lipidosome has the adhesion capacity similar to the adhesion capacity of a pure platelet vesicle to collagen and fibrinogen; in-vitro targeting experiment results prove that the platelet-like liposome has good targeting similar to the targeting of the pure platelet vesicle to tumor cells; pharmacokinetic experiment results prove that the platelet-like lipidosome has long in-vivo circulation time close to the in-vivo circulation time of a traditional lipidosome; and in-vivo targeting experiment results prove that the platelet-like lipidosome has a targeting effect significantly higher than the targeting effect of a traditional lipidosome and the pure platelet vesicle on residual tumors and metastatic tumors.

Description

Technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to a targeted drug delivery system, in particular to a platelet-like liposome drug delivery system and a preparation method and application thereof. Background technique [0002] The prior art discloses that the main clinical treatment for solid tumors is still surgical treatment. Practice has proved that residual tumor tissue and circulating tumor cells caused by surgical resection have always been the key to severely affecting the prognosis of tumor treatment. Studies have shown that death caused by tumor recurrence and metastasis has become a very serious challenge for tumor treatment. Therefore, it is very important to develop tumor treatment options for postoperative residual tumors and circulating tumor cells to reduce or prevent tumor recurrence and metastasis. The clinical significance. [0003] Clinical practice shows that most of the chemotherapeutics in the clinic have ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K47/46A61K47/24A61P35/00A61P35/04
CPCA61K9/1271A61K9/1277A61K47/46A61K47/24A61P35/00A61P35/04
Inventor 庞志清罗子淼
Owner FUDAN UNIV
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