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A kind of preparation method of pH-sensitive carbon nanotube targeted drug delivery system

A carbon nanotube and targeting technology, which is applied in the field of medicine to achieve the effects of increased dispersion and biocompatibility, good anti-tumor effect, and obvious tumor cell targeting ability

Active Publication Date: 2017-07-07
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] So far, there has been no report on the use of RGD peptides in carbon nanotube drug delivery systems. At the same time, as a tumor drug delivery system, pH responsiveness and excellent biocompatibility are required.

Method used

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  • A kind of preparation method of pH-sensitive carbon nanotube targeted drug delivery system
  • A kind of preparation method of pH-sensitive carbon nanotube targeted drug delivery system
  • A kind of preparation method of pH-sensitive carbon nanotube targeted drug delivery system

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Embodiment 1

[0037] Example 1: Preparation of pH-sensitive carbon nanotube targeted drug delivery system

[0038] (1) Add single-walled carbon nanotubes with a length of 1-5 µm to a strong acid mixed solution ( 98% H 2 SO 4 and 65%HNO 3The volume ratio is 1:1 ), ultrasonically dispersed for 30 min, condensed and refluxed for 8 h under mechanical stirring in an oil bath at 80°C, cooled and left for a period of time after the reaction, the upper layer of acid solution was removed and diluted with distilled water, filtered through 0.22 μm mixed cellulose Membrane vacuum filtration, the filter cake was washed with a large amount of deionized water until the pH of the filtrate was neutral, and vacuum-dried at 50°C to obtain truncated oxidized single-walled carbon nanotubes (SWCNT);

[0039] (2) Disperse the oxidized single-armed carbon nanotubes in docetaxel (DTX) methanol solution, the mass ratio of the drug to the oxidized single-armed carbon nanotubes was 1:3; the mixture solution was son...

Embodiment 2

[0044] Embodiment 2: drug release experiment in vitro

[0045] RGD-CS-SWCNT-DTX and DTX were dispersed in PBS containing 0.5% Tween solution at pH 7.4 and pH 5.0, respectively, so that the concentration of DTX in the above four samples was kept consistent (70 μg / mL). Take 2 mL of the sample solution and place them in dialysis bags with a molecular weight cut-off of 8KD, clamp the dialysis bags with dialysis clamps, put them into the corresponding 40 mL of PBS buffer solution, and place them in a horizontal constant temperature oscillator at 37°C for dynamic analysis. Dialyze (frequency 100 r / min), start timing, take 0.5 mL of dialysate after a certain period of time, and supplement 0.5 mL of fresh PBS solution at the same time, parallel 3 samples and calculate the cumulative release. After the samples were centrifuged, the content of DTX was determined by HPLC. image 3 It is the release curve of the drug in the functionalized SWCNT drug-loaded system. From the release curve,...

Embodiment 3

[0046] Embodiment 3: In vitro test of tumor cells

[0047] (1) Cell culture: non-small cell lung cancer A549 cells with high integrin receptor expression and breast cancer MCF-7 cells with low expression were selected, and A549 cells were cultured with PRMI-1640 medium containing 10% fetal bovine serum (FBS). MCF-7 cells were cultured in DMEM medium containing 10% FBS high glucose at 37°C, 5% CO 2 cultured in an incubator.

[0048] (2) Detection of tumor cell survival rate: A549 and MCF-7 cells in the logarithmic growth phase were taken, and 8×10 4 cells / mL were seeded in 96-well culture plates, and the prepared carbon nanotube drug delivery complexes (SWCNT-DTX, CS-SWCNT-DTX, RGD-CS-SWCNT-DTX) and raw drug DTX were added to the In the growth phase of A549 and MCF-7 cells, at 37°C, 5% CO 2 Conditioned for 48h. Wash twice with PBS when the culture is terminated, add 90 μl of medium and 10 μl of MTT to each well and continue to incubate for 4 hours, discard the supernatant, ...

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Abstract

The invention belongs to the technical field of medicines and particularly relates to a preparation method for a pH-sensitive carbon nano tube-targeted drug delivery system. The preparation method comprises the following steps: adopting a carbon nano tube which is oxidized by adopting mixed acid as a carrier, loading an anti-tumor drug on the surface of the carbon nano tube by virtue of Pi-Pi effect; and then, adopting chitosan coupled by RGD (arginine-glycine-aspartic acid) to further modify the surface of the carbon nano tube to obtain a pH-sensitive carbon nano tube-targeted drug delivery carrier. The carbon nano tube carrier is high in drug loading capacity, the drug is delivered to tumor cells by virtue of dual effects of chitosan modification and RGD-targeted guiding, so that the drug is promoted to release in a low-pH tumor cell environment, and thus, the drug concentration in tumor tissue is increased, the tumor cells are killed, the anti-tumor effects are increased, and the toxic and side effect is lowered. The preparation method disclosed by the invention is simple in operation, gentle in preparation condition, easily available and reliable to obtain products, simple in posttreatment, and suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of medicine and relates to the preparation of a drug targeting delivery system, in particular to a preparation method of a pH-sensitive carbon nanotube targeting drug delivery system. Background technique [0002] Malignant tumors are one of the common diseases that seriously threaten human life and health in the world today. At present, the main treatment methods include surgery, chemotherapy and radiotherapy. Chemotherapy is a common treatment method for tumors. Since most antitumor drugs lack specificity to tumor cells, chemotherapy kills tumor cells as well as normal cells, resulting in severe side effects. After chemotherapy drugs enter the systemic blood circulation through injection, they have to go through steps such as protein binding, metabolism, and excretion, and less drugs reach the tumor site. To increase the concentration of chemotherapeutic drugs in tumor tissue, it is necessary to increase...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/18A61K47/36A61K47/52A61P35/00
Inventor 曹青日徐卫娟崔京浩
Owner SUZHOU UNIV
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