Nano-particle with excellent blood stabilizing performance, and preparation method thereof

A nanoparticle and performance-stabilizing technology, applied in the field of nanoparticles and their preparation, can solve the problems of limiting the use of nano-drugs and the inability to significantly improve the bioavailability of nano-drugs, achieving good blood stability and improving blood circulation stability. and highly controllable effect of cycle time and particle size

Active Publication Date: 2018-09-18
SUN YAT SEN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] However, after intravenous injection into the blood, more than 80% of the nano-drugs will be captured and metabolized by the reticuloendothelial system...

Method used

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  • Nano-particle with excellent blood stabilizing performance, and preparation method thereof
  • Nano-particle with excellent blood stabilizing performance, and preparation method thereof
  • Nano-particle with excellent blood stabilizing performance, and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Example 1 Preparation of nanoparticles loaded with indocyanine green (ICG) by rapid nanoprecipitation technique

[0036] In this example, ICG-loaded nanoparticles with three particle sizes were prepared by adjusting the volume ratio of the aqueous phase / organic phase and the liquid flow rate of the channel. The specific implementation steps are as follows:

[0037]1. The specific implementation steps of nanoparticle 1: ① Dissolve 6 mg PLGA and 0.6 mg ICG in 3 mL organic solvent acetonitrile, vortex and mix well; dissolve 15 mg PF127 and 1 mg DSPE-PEG in 3 mL ultrapure water, Shake and mix; ② Acetonitrile solution containing PLGA and ICG passes through channel 1 (flow rate 10 mL / min), aqueous solution containing PF127 and DSPE-PEG passes through channel 2 (flow rate 10 mL / min), 12 mL ultrapure water passes through channel respectively 3 and 4 (both flow rates are 40 mL / min), transported to a multi-channel vortex mixer for high-speed mixing and solvent exchange to obtain ...

Embodiment 2

[0041] Example 2 Verification of the system stability of nanoparticles in phosphate buffered saline (PBS) and DMEM medium (containing 10% fetal bovine serum)

[0042] In this example, taking the nanoparticles 1, 2, and 3 prepared in Example 1 as examples, the particle size stability and entrapped fluorescence of the three nanoparticles in PBS and DMEM medium (containing 10% fetal bovine serum) were explored. The fluorescence stability of the probe, the specific implementation steps are as follows:

[0043] Take the solutions of NP-1, NP-2 and NP-3 loaded with ICG, add the three solutions into PBS (pH=7.4) and DMEM medium containing 10% fetal bovine serum) respectively, and incubate at 37°C For 5 days, track and test the particle size of the nanoparticles and the fluorescence intensity value of the particles at 810nm every day, the results are as follows Figure 4~5 shown.

Embodiment 3

[0044] Example 3 Detection of long-term circulation stability of nanoparticles in blood

[0045] This example aims to detect the half-life of nanoparticles in blood, and provide basic research evidence for the biological application of nanoparticles to prolong the effective delivery of drugs or molecular probes. The specific implementation steps are as follows:

[0046] Twelve BALB / c mice were randomly divided into 4 groups, 3 mice in each group; ②Inject free ICG, NP-1, NP-2 and NP-3 into the mice through tail vein injection; ③In the Collect 0.1 mL of mouse blood at 5 / 15 / 30 minutes and 1 / 2 / 4 / 8 / 16 / 24 / 48 hours, and mix it well with 0.1 mL PBS (containing 1 mg / mL heparin sodium) for detection; ④ according to For the absorption peak of ICG at 780 nm, use a multifunctional microplate reader to detect the absorption value of the sample at 780 nm; ⑤ Prepare ICG concentrations of 10 -5 mg / mL, 5×10 -5 mg / mL, 2×10 -4 mg / mL, 10 -3 mg / mL and 5×10 -3 mg / mL PBS solution with 5 gr...

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Abstract

The invention belongs to the technical field of nano-medicines, and provides a nano-particle with an excellent blood stabilizing performance, and a preparation method thereof. Poly(glycolide-co-lactide) (PLGA), a medicine/probe molecule, distearoyl phosphoethanolamine-polyethylene glycol-maleimide (DSPE-PEG) and pluronic F127 (PF127) which are used as raw materials undergo a rapid nanoprecipitation technique to prepare the nano-particle having the advantages of controlled particle size, good monodispersity, and excellent stability and performances in various solutions. A large number of hydroxyl groups and negative charges on the surface of the particle have a protection effect, so the nano-particle do not bind to proteins in serum, thereby the protein is avoided from being absorbed and metabolized by the reticuloendothelial system; and the hydrophobic medicine and the hydrophobic or amphipathic probe are encapsulated, so the particle can significantly prolong the blood circulation half-life of the medicine and the probe, and provides a good medicine delivery platform for disease detection and treatment.

Description

technical field [0001] The invention relates to the technical field of nanomaterials, in particular to a nanoparticle with excellent blood stability and a preparation method thereof. Background technique [0002] Clinically, intravenous injection or infusion is often used to deliver drugs into the body for disease treatment. However, after the drug enters the blood circulation, a large part will be captured by the protein in the blood and transported to the liver and kidney for metabolism through the reticuloendothelial system, and finally excreted from the body, resulting in extremely low bioavailability of the drug, and has immunosuppression, tissue damage and neurotoxic side effects. With the continuous advancement of nanotechnology and medicine, a large number of nanomedicines have been designed to achieve targeted drug delivery (such as folic acid and other small molecules, vascular endothelial growth factor receptors, etc.) Drug side effects, improve drug bioavailabi...

Claims

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Application Information

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IPC IPC(8): A61K9/50A61K47/34A61K47/24A61K47/10A61P35/00
CPCA61K9/5031A61P35/00
Inventor 赵鹏飞陈永明曾志鹏
Owner SUN YAT SEN UNIV
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