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BCG (bacillus calmette-guerin) vaccine complex combined with nano drug carrier and preparation method of BCG vaccine complex

A nano-drug carrier, BCG technology, which is applied in the direction of drug combination, pharmaceutical formula, polymer compound non-active ingredients, etc., can solve the problems of insufficient drug absorption, short drug retention time, etc., to achieve enhanced uptake and tumor targeting, Good adhesion and absorption, enhance the effect of tumor killing effect

Pending Publication Date: 2021-03-09
THE SECOND HOSPITAL OF TIANJIN MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the biggest problem with intravesical administration is that the drug stays in the bladder for a short time and the drug is not fully absorbed.

Method used

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  • BCG (bacillus calmette-guerin) vaccine complex combined with nano drug carrier and preparation method of BCG vaccine complex
  • BCG (bacillus calmette-guerin) vaccine complex combined with nano drug carrier and preparation method of BCG vaccine complex
  • BCG (bacillus calmette-guerin) vaccine complex combined with nano drug carrier and preparation method of BCG vaccine complex

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0021] Step 1. Preparation of nano-drug carriers: mainly by using W / O / W emulsification method and ultrasonic emulsification technology to realize the preparation of polymer PLGA-coated nano-drug carriers. For drugs that are easily soluble in organic solvents, pre-mix with PLGA in dichloromethane DCM solution, then mix with water, perform ultrasonic emulsification, and finally obtain PLGA double emulsion to obtain PLGA-coated nano-drugs carrier particles. For drugs that are easily soluble in water but not easily soluble in various types of organic solvents, the drug is directly dissolved in the water phase, and then directly phacoemulsified with the DCM organic phase of PLGA. The nano drug carrier is a spherical particle, which has the characteristics of high biological safety, small particle size, uniform distribution and the like. Using this method, the preparation of nano-carriers of different drugs can be realized.

[0022] Step 2, the combination of nano-drug carrier and...

Embodiment 1

[0025] Embodiment 1: The preparation process of the BCG complex combined with the PLGA nano drug carrier coated with Dox molecules is illustrated below by taking the common clinical chemotherapy drug doxorubicin (Dox) as an example.

[0026] Step 1, the preparation of Dox nano drug carrier:

[0027] 10 mg of organic material PLGA was weighed and dissolved in the organic phase of dichloromethane (DCM) to prepare a DCM solution of PLGA with a concentration of 10 mg / ml. Weigh 1 mg of the chemotherapeutic drug Dox and dissolve it in dimethyl sulfoxide (DMSO) to prepare a DMSO solution of Dox with a concentration of 10 mg / ml. Take 0.9ml of PLGA solution and mix it with 0.1ml of Dox solution, and shake it ultrasonically for 30min in a water bath at 20°C to make it fully mixed. Then slowly add the above mixed solution into 1ml of polyvinyl alcohol (PVA) solution with a mass volume ratio of 0.5%, and use a probe ultrasonic homogenizer to ultrasonicate for 2 minutes (power of 30W, fre...

Embodiment 2

[0035] Example 2: The killing effect of BCG-NPs on human bladder cancer T-24 cell line in vitro:

[0036] Compared with BCG alone, the killing ability of the synthesized BCG-NPs complex on human bladder cancer T-24 cell line was detected by MTT assay. The experiment was divided into two groups, namely, group A and group B. Group A took the BCG bacterial liquid in the logarithmic growth phase, and group B used the BCG-NPs suspension prepared by the present invention.

[0037] Adjust the bacterial concentration to 10 with PBS 8 CFU / ml. Take 10ul, 50ul, and 100ul of each group's bacterial solution (referring to group A and group B) respectively, and add them to a 96-well cell culture plate covered with bladder cancer T-24 cells, and each group of experiments is set to repeat in triplicate. The negative control group was added with the same volume of PBS. 37°C, use 1640-cell complete medium in a cell culture incubator, and culture for 24 hours. After the culture is over, discar...

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Abstract

The invention discloses a BCG (bacillus calmette-guerin) vaccine complex combined with a nano drug carrier. The BCG vaccine complex is of a complex structure formed by combining the nano drug carrierand BCG vaccine thalli by virtue of an acting force between avidin and biotin protein; the nano drug carrier is nano particles which are coated with a polylactic acid-glycolic acid copolymer, subjected to surface modification by the avidin and have the particle size of 120nm to 180nm; and the surface of each BCG vaccine thallus is combined with one or more nano particles. The BCG vaccine complex disclosed by the invention has very good adhesion and absorption effects on the epithelial layer of the bladder, drug particles are loaded to the surfaces of the BCG thalli, and the BCG is used as thecarrier, so that the uptake of the nano drug carrier in the bladder and tumor targeting are enhanced, and the tumor killing effect of a drug can be remarkably improved. Meanwhile, the drug-loaded BCGcan stimulate strong immune response in part of the bladder and the whole body, so that a combined treatment mode combining immunotherapy and chemotherapy is realized.

Description

technical field [0001] The invention belongs to nano drug carrier technology, in particular to a BCG complex combined with a nano drug carrier and a preparation method thereof. Background technique [0002] Bladder cancer is the second most common malignant tumor in the urinary system, and non-muscle invasive (NMIBC) patients account for more than 70% of all newly diagnosed bladder cancer patients. The high rate of tumor recurrence and progression is the most important factor affecting the prognosis of bladder cancer patients. Intravesical Bacillus Calmette-Guerin ((BCG Vaccine)) infusion is the recommended postoperative treatment for high-risk NMIBC patients and has been widely used clinically. Intravesical BCG perfusion can induce a strong local immune response in the body to kill surgical residues or tiny tumor lesions, thereby significantly reducing the recurrence and progression of cancer and improving the prognosis of patients. Although the immunotherapy effect of BC...

Claims

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Application Information

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IPC IPC(8): A61K47/46A61K47/34A61K47/42A61K45/00A61P35/00
CPCA61K47/46A61K47/34A61K47/42A61K45/00A61P35/00
Inventor 牛远杰赵阳刘康康尚芝群孙二琳马媛王丽宁
Owner THE SECOND HOSPITAL OF TIANJIN MEDICAL UNIV
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