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Novel blood brain barrier-crossing drug delivery system and preparation method and application thereof

A technology of blood-brain barrier and delivery system, which is applied in the direction of drug combination, pharmaceutical formula, antineoplastic drugs, etc., can solve the problems of poor curative effect of glioma chemotherapy, achieve good drug delivery effect, avoid pain, and be easy to operate

Active Publication Date: 2020-05-08
TIANJIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, the inherent sensitivity of tumors to drugs, the limited absorption of tumor cells to drugs, intracellular drug metabolism and cellular drug resistance mechanisms are all important reasons for the poor efficacy of glioma chemotherapy.

Method used

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  • Novel blood brain barrier-crossing drug delivery system and preparation method and application thereof
  • Novel blood brain barrier-crossing drug delivery system and preparation method and application thereof
  • Novel blood brain barrier-crossing drug delivery system and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Example 1: Preparation of polydopamine nanoparticles. Mix 3 milliliters of ammonia water, 40 milliliters of ethanol, and 90 milliliters of distilled water, and stir for 30 minutes at a temperature of 30 degrees Celsius and a magnetic stirrer speed of 500 rpm. After stirring, take 0.5 gram of dopamine hydrochloride and dissolve it in 10 milliliters of ultrapure water, and add it to the solution described in step 1), at a temperature of 30 degrees Celsius and a magnetic stirrer speed of 500 rpm , reacted for 24 hours. After the reaction, centrifuge (13800 rev / min) with high-speed centrifuge and wash with water, repeat three times.

[0033] The polydopamine nanoparticles have a diameter of 176.24 nanometers and a potential of -51.5 millivolts.

Embodiment 2

[0034] Example 2: Preparation of polydopamine nanoparticles, 75 mg of dopamine hydrochloride was weighed and dissolved in 55 ml of ultrapure water, and 350 microliters of 1 mole per liter of sodium hydroxide solution was added dropwise to adjust the pH of the solution to 8.5. The mixture was reacted for 5 hours at a temperature of 45 degrees Celsius and a magnetic stirrer with a rotational speed of 500 rpm. After the reaction, centrifuge (13800 rev / min) with high-speed centrifuge and wash with water, repeat three times.

[0035] The polydopamine nanoparticles have a diameter of 135.34 nanometers and a potential of -30.9 millivolts.

Embodiment 3

[0036] Example 3: Preparation of polydopamine nanoparticles, 10 mg of dopamine hydrochloride was weighed and dissolved in 30 ml of 100 mmol / L tris buffer solution, the pH of the solution was controlled to be 8.5, and the reaction was carried out for 6 hours. After the reaction, centrifuge (13000-20000 revolutions per minute) and wash with water, repeat three times.

[0037] The polydopamine nanoparticles have a diameter of 160.83 nanometers and a potential of 22.8 millivolts.

[0038] figure 1 The particle size diagrams of polydopamine nanoparticles prepared in Experimental Examples 1-3 are shown; Examples 1-3 correspond to methods 1, 2, and 3, respectively.

[0039] Example 2 is the optimal example, and Example 2 is used as the preparation method of polydopamine nanoparticles to prepare highly efficient drug-loading composite nanomicelles for glioma:

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Abstract

The present invention belongs to the field of drug delivery systems and particularly relates to a novel blood brain barrier-crossing drug delivery system and a preparation method and an application thereof. The ovel blood brain barrier-crossing drug delivery system comprises micelles of polydopamine nanoparticles encapsulated by amphiphilic peptides. The micelles have a diameter of 160-270 nanometers and a potential of 10-30 millivolts. The polydopamine nanoparticles have a diameter of 120-200 nanometers and a potential of -60 to 40 millivolts. The novel blood brain barrier-crossing drug delivery system has the following advantages (1) the drug delivery system is good in biocompatibility and biodegradability; (2) the drug delivery system is easy in operation and controllable in synthesis,so that the nanoparticles can be produced on a large scale; (3) the drug delivery system has powerful functionalization ability, so that the nanoparticles are easily modified by certain targeting molecules and have a good drug delivery effect; and (4) the drug delivery system has relatively high diagnostic and treatment efficiency.

Description

technical field [0001] The invention belongs to the field of drug delivery systems, and in particular relates to a novel cross-blood-brain barrier drug delivery system and its preparation method and application. Background technique [0002] One of the most common and aggressive primary brain malignancies is glioma arising from glial cells, and the treatment of these malignant gliomas is one of the most daunting challenges in oncology. Despite the combination of radiotherapy, chemotherapy and surgery, the prognosis of patients with malignant glioma is still poor, with an average survival period of 15 to 22 months. Due to the infiltrative growth of glioma, it is difficult to completely resect the tumor while preserving important brain functions. Non-invasive treatment is a promising direction to improve the living conditions of glioma. However, one of the most notable hurdles behind the disappointing results in glioma treatment is the presence of the blood-brain barrier (BB...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/107A61K47/42A61K47/34A61K41/00A61P35/00
CPCA61K9/1075A61K47/42A61K47/34A61K41/0052A61P35/00
Inventor 刘哲张晨刘晨熙何文心焦典
Owner TIANJIN UNIV
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