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Hyaluronic acid-modified silicon-encapsulated drug-loading phospholipid liquid fluorocarbon nanosphere ultrasonic contrast agent and preparation method thereof

A technology of hyaluronic acid modification and ultrasound contrast agent, which is applied in the field of medical medicine, can solve the problems of complex process and poor stability, and achieve the effect of simple synthesis process, less time-consuming, and good biocompatibility

Inactive Publication Date: 2017-09-29
CHONGQING MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] The purpose of the present invention is to solve the problems that phospholipid liquid fluorocarbon nanospheres have poor stability as an ultrasound contrast agent and the existing silicon-wrapped liquid fluorocarbon nanospheres have a complicated process, and use docetaxel as a model drug to provide a new transparent Silicon-coated drug-loaded phospholipid-modified silicon-coated liquid fluorocarbon nanosphere ultrasound contrast agent and preparation method thereof

Method used

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  • Hyaluronic acid-modified silicon-encapsulated drug-loading phospholipid liquid fluorocarbon nanosphere ultrasonic contrast agent and preparation method thereof
  • Hyaluronic acid-modified silicon-encapsulated drug-loading phospholipid liquid fluorocarbon nanosphere ultrasonic contrast agent and preparation method thereof
  • Hyaluronic acid-modified silicon-encapsulated drug-loading phospholipid liquid fluorocarbon nanosphere ultrasonic contrast agent and preparation method thereof

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Embodiment 1

[0027] 1. Preparation of Phospholipid Liquid Fluorocarbon Nanospheres

[0028] 30 mg soybean lecithin (SPC) and 3 mg drug were dissolved in 2 mL dichloromethane. The dichloromethane was quickly removed by evaporation under reduced pressure, forming a lipid film. After adding 8 mL of phosphate buffer (pH 7.4), the lipid film was hydrated in an ultrasonic water bath for 5 minutes to obtain a crude milk. The rough milk was sonicated for 10 min with an ultrasonic cell breaker, and cooled in a refrigerator at 4° C. to obtain liposomes. Add 0.06 mL of PFP to the liposome suspension, and then use an ultrasonic cell disruptor to sonicate for 5 minutes under ice bath conditions to obtain drug-loaded phospholipid liquid fluorocarbon nanospheres.

[0029] 2. Preparation of aminated silicon-coated drug-loaded phospholipid liquid fluorocarbon nanospheres

[0030] Dilute 8 mL of phospholipid liquid fluorocarbon nanosphere suspension to 24 mL, adjust the pH to 8.5 with dilute ammonia wate...

Embodiment 2

[0035] 1. In vitro heating-induced phase transition microscope observation of hyaluronic acid-modified silicon-coated phospholipid liquid fluorocarbon nanospheres ultrasound contrast agent

[0036] The prepared hyaluronic acid-modified silicon-coated drug-loaded phospholipid liquid fluorocarbon nanosphere ultrasound contrast agent suspension was added to a centrifuge tube, and then the centrifuge tube was put into a water bath, and the temperature was monitored with a thermometer. , 35, 45, 55, 65, 70°C) for 5 minutes, and then observe the morphology under an optical microscope. see results Figure 4 , the results show that when the temperature is lower than 55 °C, almost no bubbles are generated. When the temperature rises to 65°C, a small amount of bubbles can be observed, and when the temperature rises to 70°C, a large number of bubbles can be observed. The particle size analysis results show that when the temperature is heated from 25 to 55°C, the particle size increases...

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Abstract

The invention discloses a hyaluronic acid-modified silicon-encapsulated drug-loading phospholipid liquid fluorocarbon nanosphere ultrasonic contrast agent and a preparation method thereof. The hyaluronic acid modified silicon-encapsulated drug-loading phospholipid liquid fluorocarbon nanosphere ultrasonic contrast agent prepared through an emulsification-silicon precipitation method has the particle size of approximately 274.5nm; the passive targeting can be realized through an EPR (Electron Paramagnetic Resonance) effect of a tumor site. Meanwhile, modifying hyaluronic acid can be also used for realizing the active targeting on a tumor cell; thus, the toxic and side effects of a preparation can be decreased; the curative effect of a drug is enhanced. On the other hand, compared with a phospholipid liquid fluorocarbon nanosphere, a hyaluronic acid modified silicon-encapsulated drug-loading phospholipid liquid fluorocarbon nanosphere prepared by the method has favorable stability and a lasting ultrasonic contrast effect. The hyaluronic acid modified silicon-encapsulated drug-loading phospholipid liquid fluorocarbon nanosphere ultrasonic contrast agent has the advantages of simple and convenient process, good biocompatibility of used materials, no use of a toxic surfactant, and wide application prospect.

Description

technical field [0001] The invention relates to the field of medical medicine, in particular to a hyaluronic acid-modified silicon-coated drug-loaded phospholipid liquid fluorocarbon nanosphere ultrasonic contrast agent and a preparation method thereof. Background technique [0002] Targeted drug delivery system is one of the hot spots in the field of pharmaceutical research. Targeted drug delivery can selectively deliver drugs to the target location, increase the curative effect and reduce the side effects of drugs on normal tissues. Hyaluronic acid (HA) is a linear polymer aminoglucan formed by linking N-acetyl-D-glucosamine and D-glucuronic acid through β-1,4 glycosidic bonds. The current research uses high molecular weight hyaluronic acid as an active targeting factor, which specifically binds to the CD44 receptor on the surface of tumor cells, mediates the entry of drugs into cells, and releases drugs in cells. HA has many advantages: good water solubility, biodegrada...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/22A61K9/51A61K47/36A61K47/24A61K31/337A61P35/00
CPCA61K9/5123A61K9/5161A61K31/337A61K49/225
Inventor 张良珂杨强
Owner CHONGQING MEDICAL UNIVERSITY
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