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Preparation method of lipid wrapped solid drug nano particle

A nanoparticle and drug technology, applied in the field of biomedicine, can solve the problem of low drug loading of nano drugs, achieve the effect of small batch-to-batch differences and great application prospects

Active Publication Date: 2018-12-07
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the nano-drugs prepared by the rapid nano-precipitation method also have the defect of low drug loading.

Method used

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  • Preparation method of lipid wrapped solid drug nano particle
  • Preparation method of lipid wrapped solid drug nano particle
  • Preparation method of lipid wrapped solid drug nano particle

Examples

Experimental program
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Effect test

Embodiment 1

[0032] The preparation of embodiment 1 methotrexate nanoparticle solution

[0033] Weigh methotrexate, dissolve in a mixed solvent of N,N-dimethylformamide and N-methylpyrrolidone (volume ratio 7:3), and prepare a 4 mg / mL organic solution of methotrexate. It is introduced into the first channel of the four-channel vortex mixer, and the other three channels are introduced with ultrapure water to achieve rapid turbulent mixing to prepare the methotrexate nanoparticle solution. The volume ratio of the methotrexate organic solution to the aqueous phase is 1:3-9, respectively, and the flow rate of the organic phase is 6 mL / min.

[0034] When changing the volume ratio of the methotrexate organic solution (organic phase) and the aqueous phase, methotrexate nanoparticles with different particle sizes can be prepared. The specific ratio and particle size relationship is as follows: figure 1 As shown, it can be seen from the figure that when the volume ratio of the organic phase to the...

Embodiment 2

[0037] Example 2 Preparation of nanoparticles of lipid-encapsulated methotrexate

[0038]Weigh 1,2-dioleoyl-SN-glycero-3-phosphoethanolamine (DOPE), cholesterol succinate monoester (CHEMS), 1,2-distearoyl-SN-glycero-3-phosphoethanolamine - Polyethylene glycol (2000) (DSPE-PEG), prepared as a mixture at a molar ratio of 10:9:1, dissolved in dichloromethane to prepare a 10 mg / mL mixed lipid solution for later use. Pipette gun to quantitatively pipette 0.1 mL of mixed lipid dichloromethane solution and add it to 10 mL of 4% ethanol solution, and the solution is sonicated with a probe ultrasonic instrument until it is clear and ready for use. After mixing the lipid ethanol solution of equal volume and the methotrexate nanoparticle solution with a particle diameter of 49.1nm prepared in Example 1, the mass ratio of methotrexate and mixed lipids in the mixed solution was 4:1, and mixed The solution was repeatedly extruded 7 times through a 100-nanometer polyvinylidene fluoride memb...

Embodiment 3

[0045] Example 3 Preparation of lipid-coated chlorambucil or doxorubicin nanoparticles

[0046] Weigh chlorambucil or doxorubicin and dissolve them in dimethyl sulfoxide or N,N-dimethylformamide respectively to make 1 mg / mL or 0.5 mg / mL organic solutions, and introduce them into The first channel of the four-channel vortex mixer, and the other three channels are introduced with ultrapure water to achieve rapid turbulent mixing to prepare the chlorambucil nanoparticle solution and the doxorubicin nanoparticle solution. Among them, the volume ratio of chlorambucil nanoparticle solution (organic phase) or doxorubicin nanoparticle solution (organic phase) to the aqueous phase was set to 1:3-11 respectively, and the flow rate of the organic phase was 10 mL / min. A chlorambucil nanoparticle solution and a doxorubicin nanoparticle solution were obtained.

[0047] Referring to the steps in Example 2, lipid-coated chlorambucil nanoparticles and lipid-coated doxorubicin nanoparticles we...

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Abstract

The invention discloses a preparation method of a lipid wrapped solid drug nano particle. The preparation method comprises following steps: at first, preparing a drug nano particle solution from an amphiphilic small molecular drug by a rapid nano precipitation method without adding any stabilizing agent; mixing the drug nano particle solution with a lipid solution, and extruding the mixed solutionto prepare the lipid wrapped solid drug nano particle. Compared with a conventional drug nano particle, the provided lipid wrapped solid drug nano particle has an ultrahigh drug loading capacity, which can reach 60% or more and is obviously higher than that of a conventional drug nano particle. Moreover, the preparation method is continuous, the difference between different batches is small, andthe preparation method is suitable for industrial production. Furthermore, the surface of the drug particle is wrapped by lipid, thus the nano particle can be stably stored for a long term, at the same time, the tumor tissue targeting performance and pH responding property are also enhanced, and the preparation method has a wide application prospect in drug delivery.

Description

technical field [0001] The invention belongs to the field of biomedicine, and more specifically relates to a method for preparing lipid-coated solid drug nanoparticles. Background technique [0002] Although the nano-chemotherapy drug delivery system has improved the curative effect and prolonged the patient's survival time to a certain extent, cancer is still one of the diseases that threaten human health the most. So far, although nano-drug preparations are being developed and produced, and even approved for clinical use, most nano-drugs have a fatal flaw, that is, their drug loading is low, usually less than 10%; in addition, some carriers used in nano-medicines have no efficacy and may even produce toxic and side effects; and the preparation process of nano-medicines often involves cumbersome processes or complex chemical synthesis, resulting in poor reproducibility of different batches and difficulty in large-scale Industrial production. [0003] Rapid nanoprecipitati...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K47/24A61K47/28A61K47/34A61K31/519A61K31/196A61K31/704A61P35/00
CPCA61K9/5123A61K9/5146A61K31/196A61K31/519A61K31/704A61P35/00
Inventor 曾志鹏陈永明刘利新赵鹏飞
Owner SUN YAT SEN UNIV
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