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Platelet membrane wrapped drug loading porous nano particle and preparation method thereof

A nanoparticle and platelet technology, applied in the field of drug-loaded nanoparticles and their preparation, can solve the problems of low drug-degrading rate of PLGA nanoparticles, low immune effect and low immunogenicity of PLGA nanoparticles, and achieve excellent results. Biocompatibility, improved biocompatibility, low immunogenicity effect

Active Publication Date: 2019-03-08
DONGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The technical problem to be solved by the present invention is to provide a platelet membrane-wrapped drug-loaded porous nanoparticle and its preparation method to overcome the defects of low drug release rate based on PLGA nanoparticles and passive targeting and immune effects in the prior art
[0005] The materials used in the present invention have excellent biocompatibility and low immunogenicity, which not only solves the problem of low drug release rate based on the slow degradation of PLGA nanoparticles, but also prevents the particles from being The reticuloendothelial system captures and actively targets the delivery of chemotherapy drugs to the tumor site, showing broad prospects for targeted therapy of cancer

Method used

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  • Platelet membrane wrapped drug loading porous nano particle and preparation method thereof
  • Platelet membrane wrapped drug loading porous nano particle and preparation method thereof
  • Platelet membrane wrapped drug loading porous nano particle and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0041] (1) Add 105 mg of PLGA to 10 mL of dimethylformamide solution containing 2.9 mg of EDC·HCl and 1.7 mg of NHS, and activate it in ice bath for 0.5 h. When the temperature was raised to room temperature, 9 mg chitosan oligosaccharide was added and reacted for 48 h under nitrogen protection. Then, it was dialyzed in PBS buffer solution with pH=7.4 for 3 days with a dialysis bag with a molecular weight cutoff of 7000, and then freeze-dried to obtain CS-PLGA.

[0042] (2) Disperse the CS-PLGA obtained in step (1), chitosan oligosaccharide, and PLGA in aqueous solutions of pH=5.0, 7.4, and 8.6 to prepare a dispersion of 0.5 mg / mL, and measure its Zeta potential respectively, as figure 2 As shown, when the pH changes from acidic to alkaline, the potential of CS-PLGA changes from positive to negative correspondingly, while the electrical properties of chitosan and PLGA do not change accordingly. The results showed that chitosan oligosaccharides were successfully bonded to PLG...

Embodiment 2

[0044] (1) Dissolve 10mg CS-PLGA and 1mg Bufalin in 1mL acetone, add dropwise to 5mLTPGS 20% (w / v) deionized water at 800rpm, stir in air for 3h, then put in a vacuum oven , to remove residual acetone. Then wash three times with deionized water to remove TPGS, and finally resuspend with the same volume of deionized water to obtain drug-loaded nanoparticles with porous structure. To set up a control, drug-loaded CS-PLGA / Bu nanoparticles without pore structures were prepared in a similar manner to that described above, except that the mixed acetone solution was added to deionized water without TPGS.

[0045] (2) Blood was collected from the heart to obtain fresh blood from female SD rats, and the anticoagulated blood was added to a centrifuge tube containing the separation solution (the volume ratio of the anticoagulation blood to the separation solution was 1:2) and centrifuged at 300 g for 15 minutes. Aspirate the first layer of platelet plasma and add it to another centrifug...

Embodiment 3

[0049] (1) Take 2ml of the CS-PLGA / Bu NPs dispersion, the CS-pPLGA / Bu NPs dispersion and the PLTM-CS-pPLGA NPs dispersion in Example 2 respectively, and pack them into dialysis bags with a molecular weight cut-off of 7000, Then they were respectively immersed in 18 mL of PBS buffer solution with pH=7.4.

[0050] (2) Transfer the above drug release system to a constant temperature shaker at 37°C with a rotation speed of 100rpm for 48h, and take 1mL at 0.25h, 0.5h, 1h, 2h, 4h, 8h, 12h, 24h, and 48h to measure its concentration at 298nm. UV absorbance was measured, and then 1 mL of PBS buffer under the same conditions was re-supplemented, data were collected and drug release was calculated.

[0051] The release profiles of Bufalin in the three granules are as follows Figure 6 shown. After 48h, the cumulative drug release of CS-PLGA / BuNPs without pore structure was less than 20%. However, the cumulative drug release rate of CS-pPLGA / Bu NPs with a porous structure is as high as...

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Abstract

The invention relates to a platelet membrane wrapped drug loading porous nano particle and a preparation method of the nano particle. The nano particle is prepared by modifying PLGA (poly (lactic-co-glycolic acid)) with chitosan oligosaccharide CS, loading Bufotalin and then wrapping with a platelet membrane. The preparation method comprises the steps of preparation of chitosan oligosaccharide modified PLGA, preparation of CS-pPLGA / Bu NPs, preparation of a platelet membrane fragment and preparation of PLTM-CS-pPLGA / Bu NPs. According to the method, the nano particle with the positively chargedsurface is prepared from CS modified PLGA; absorption of the negatively charged platelet membrane is facilitated by a layer-by-layer self-assembly manner; the stability of the nano particle is improved; and the prepared platelet membrane bionic coated porous nano particle is expected to achieve excellent biocompatibility, low immunogenicity and active cancer cell targeting ability, can actively deliver chemotherapeutics to tumor cells in a targeted manner, improves a treatment effect and has a very good practical value.

Description

technical field [0001] The invention belongs to the field of drug-loaded nanoparticles and a preparation method thereof, in particular to a platelet membrane-wrapped drug-loaded porous nanoparticle and a preparation method thereof. Background technique [0002] Poly(lactic-co-glycolic acid) (PLGA) has been widely used in the delivery of cancer chemotherapy drugs due to its good biocompatibility and biodegradability. However, due to its slow degradation time, high hydrophobicity and too dense nanoparticle structure, after the chemotherapy drugs carried by PLGA are injected into the body, the released drugs often cannot reach the effective dose to kill cancer cells. To solve this problem, porous PLGA-based nanoparticles were prepared using TPGS as a porogen, which enhanced the drug release rate (Zhu H, Chen H, Zeng X, et al. Co-delivery of chemotherapeutic drugs with vitamin E TPGS by porous PLGA Nanoparticles for enhanced chemotherapy against multi-drug resistance [J]. Bioma...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K47/34A61K47/36A61K47/46A61K31/585A61P35/00
CPCA61K9/5153A61K9/5161A61K9/5176A61K9/5192A61K31/585A61P35/00
Inventor 朱利民王海军谢晓田
Owner DONGHUA UNIV
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