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Red cell membrane encapsulated polyester-type As2O3-supported nano particles and preparation method thereof

A technology of arsenic trioxide and red blood cell membranes, which is applied in the direction of medical formulas, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., can solve problems such as digestive tract discomfort, complicated preparation process, liver and kidney function damage, and achieve Reduce blood concentration, significantly slow-release effect, reduce toxicity

Active Publication Date: 2017-07-14
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the existing dosage forms have the following disadvantages: direct intravenous injection of arsenic trioxide is highly toxic, mainly manifested as digestive tract discomfort, liver and kidney dysfunction, cardiotoxicity, serous cavity effusion, peripheral neuritis, skin pigmentation and rash, etc.
[0003] The above studies have reduced the instantaneous blood concentration of arsenic trioxide to a certain extent, thereby reducing the toxicity to a certain extent, but at the same time, there are also shortcomings such as complicated preparation process and poor biocompatibility of the carrier materials used.

Method used

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  • Red cell membrane encapsulated polyester-type As2O3-supported nano particles and preparation method thereof
  • Red cell membrane encapsulated polyester-type As2O3-supported nano particles and preparation method thereof
  • Red cell membrane encapsulated polyester-type As2O3-supported nano particles and preparation method thereof

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Experimental program
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Effect test

Embodiment 1

[0034] Example 1. Red blood cell membrane preparation (the prepared red blood cell membrane corresponds to an equal volume of whole blood):

[0035] (1) Rats were taken, weighed, anesthetized by intraperitoneal injection of chloral hydrate at 100g / 0.7mL, and whole blood was collected by cardiac puncture;

[0036] (2) Divide the blood into EP tubes containing 0.05mL heparin sodium, 1mL per tube, centrifuge at 3800r / min for 10min at 4°C to remove the supernatant and white blood cell layer, and dilute to 1mL with PBS solution, mix well, 3800r / min Min, 7min, wash twice at 4°C, and finally dilute to 1mL with PBS.

[0037](3) Divide each tube of the mixed solution obtained in the above step (2) into four EP tubes containing 0.01 mL of heparin sodium, then add 0.9 mL of EDTA solution, and mix well. Gently blow to break the wall, add 0.1mL 10 times concentration of PBS to mix, 13200r / min, 10min, 4°C centrifuge to wash, remove the supernatant, repeat this process more than three tim...

Embodiment 2

[0040] Embodiment 2. nanoparticle material, oil phase solvent screening

[0041] Preparation by double emulsion method: take 1mL of 10mg / mL polyester material solution, slowly add it into 10mL of the external aqueous phase containing emulsifier under the condition of magnetic stirring, ultrasonication for 2min, and magnetic stirring for 3h to evaporate the organic solvent to form nanoemulsion. The prepared nanoemulsion was put into a dialysis bag with a permeation molecular weight of 30,000, and was dialyzed for 2 hours to remove free drugs to obtain a nanoparticle suspension. Particle size and polydispersity index (PDI) were measured with a Malvern laser particle size analyzer. According to the same preparation method as above, the types and solvents of each material are investigated in the following table 1:

[0042] Table 1

[0043]

[0044] From the screening results of the single factor method in Table 1, it can be seen that the molecular weight of PLGA and PLGA-PE...

Embodiment 3

[0045] Embodiment 3.RBCM-PLGA-ATO-NP preparation

[0046] Add 2mL of arsenic trioxide aqueous solution to the PLGA acetone solution, sonicate until a homogeneous phase is formed, slowly add it into the external aqueous phase containing emulsifier under the condition of magnetic stirring, and evaporate the organic solvent by magnetic stirring to form a nanoemulsion. Rotary evaporate to 1-2mL, add the prepared red blood cell membrane, sonicate, put the nano solution into a dialysis bag (MW 3000), dialyze for 2 hours to remove free drug, and obtain the nanoparticle suspension encapsulated by the red blood cell membrane.

[0047] Described PLGA molecular weight is 3000-95000, and lactic acid: glycolic acid polymerization ratio is 50:50; PLGA consumption is 10mg; The volume of PLGA acetone solution is 1mL;

[0048] The consumption of described arsenic trioxide is 1mg, and the volume of inner aqueous phase is 0.1mL;

[0049] The emulsifier is Paloxamer 188, the dosage is 3 mg, an...

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Abstract

The invention discloses a red cell membrane encapsulated polyester-type As2O3-supported nano particles and a preparation method thereof. The nano particle employs the red cell membrane as shell and a polyester-type material as a core. The polyester-type material is supported with the As2O3. The particle size of the nano particle is about 200 nm. The nano particle has a round shape and is uniformly distributed, has a clear core-shell structure and good stability, is free of causing hemolysis and agglutination of red cells and can be used in intravenous injection. The drug delivery system, compared with a free medicine, has significantly sustained releasing effect, and can solve the problem of quick increase of blood concentration after intravenous injection of the As2O3. Because that substances, being 3-400 nm in size, are generally not discharged from kidney or a rejection system, so that the drug delivery system has advantages in circulation in blood system and achieves passive targeted effects; the blood concentration of a toxic medicine is reduced and further toxicity is reduced, so that a new strategy for development of toxic antitumor medicine preparations is provided.

Description

technical field [0001] The invention relates to the technical field of pharmacy, in particular to a red blood cell membrane-encapsulated polyester-based arsenic trioxide-loaded nanoparticle and a preparation method thereof. Background technique [0002] Arsenic trioxide (ATO) is a mineral drug approved by the FDA for the treatment of acute promyelocytic leukemia (APL). It can induce cell differentiation and apoptosis, degrade PML-RARα, clear LIC, and inhibit tumor cells. Multiple pathways such as proliferation and inhibition of angiogenesis exert anti-tumor effects. It has been used to treat APL for more than 20 years, and clinical research shows that the complete remission rate can reach 90%, and there is no cross-resistance with commonly used drugs. Therefore, As 2 o 3 It has become the drug of choice for relapsed and refractory APL. Listed As for APL 2 o 3 The dosage forms include "sodium chloride arsenite injection", "arsenic trioxide injection", and "arsenic trioxi...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K9/52A61K47/46A61K47/34A61K33/36A61P35/00
CPCA61K9/0002A61K9/5153A61K9/5184A61K33/36
Inventor 邱明丰刘哿吚苏靖袁伟恩张然
Owner SHANGHAI JIAO TONG UNIV
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