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Dual-pH sensitive drug carrier system and preparation method thereof

A carrier system and drug technology, applied in the direction of drug combination, medical formula, medical preparations of non-active ingredients, etc., can solve the problems of releasing drugs and drug carriers are difficult to reach the tumor site, so as to reduce toxic and side effects, and effectively treat cancer cells The effect of internal targeted drug delivery ability, improving drug utilization and encapsulation efficiency

Active Publication Date: 2019-12-03
HUBEI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the complex environment in the cell body, it is difficult for the drug carrier to reach the tumor site, so that the drug cannot be released in the cell.

Method used

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  • Dual-pH sensitive drug carrier system and preparation method thereof
  • Dual-pH sensitive drug carrier system and preparation method thereof
  • Dual-pH sensitive drug carrier system and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] A preparation method of a double pH-sensitive drug carrier system, specifically comprising the following steps:

[0051] 1. Loading doxorubicin on hollow manganese dioxide and grafting chitosan

[0052] Disperse 20mg chitosan (CHI) in 120mL deionized water, adjust to 5-6 with acetic acid to obtain solution a; 200mg hollow manganese dioxide H-MnO 2 Disperse in 80mL deionized water, add 100mg DOX, and stir vigorously at 25°C for 24h in the dark to obtain solution b; then add solution a dropwise, react at 25°C for 2.5h, centrifuge, wash and dry to obtain grafted chitosan Sugar and doxorubicin-loaded hollow manganese dioxide (DOX@H-MnO 2 -CHI).

[0053] 2. Modification of monobenzaldehyde-terminated polyethylene glycol

[0054] Accurately weigh 200mg of DOX@H-MnO 2 -CHI, ultrasonically dispersed in 50mL aqueous solution, add one or two drops of dilute hydrochloric acid to adjust the pH to 7-8, then add 200mg of mPEG-CHO to dissolve, continue to react at 25°C for 72h, ce...

Embodiment 2

[0060] A method for preparing a composite nano drug carrier system, specifically comprising the following steps: accurately weighing 200 mg of DOX@H-MnO 2 -CHI, ultrasonically dispersed in 50mL of PBS (pH 7.4) phosphate buffer solution, then added 200mg of mPEG-CHO to dissolve, continued reaction at 25°C for 72h, centrifuged, washed and dried to obtain DOX@H-MnO 2 -CHI-PEG.

Embodiment 3

[0062] A method for preparing a composite nano drug carrier system, specifically comprising the following steps: accurately weighing 200 mg of DOX@H-MnO 2 -CHI, ultrasonically dispersed in 100mL of PBS (pH 7.4) phosphate buffer solution, then added 100mg of mPEG-CHO to dissolve, continued to react at 25°C for 72h, centrifuged, washed and dried to obtain DOX@H-MnO 2 -CHI-PEG.

[0063] The detection method of each intermediate product and final product obtained in Example 2-3 is the same as that of Example 1, and it has been verified that the drug carrier system has been successfully prepared, which has dual pH sensitivity and good targeting, and the drug itself has no large Under the gradual acid activation, it can release the drug well and cause the apoptosis of cancer cells. Therefore, the drug carrier system of the present invention has good dual pH sensitivity and high-efficiency targeted drug delivery ability in cancer cells, which can effectively improve drug utilization...

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Abstract

The invention discloses a dual-pH sensitive drug carrier system which is prepared by the following steps of modifying the surface of H-MnO2 encapsulating adriamycin (DOX) as an anticancer drug with a"valve" chitosan (CHI) to block a pore channel; and then, binding benzaldehyde terminated polyethylene glycol (mPEG-CHO) to CHI through an imine bond to prepare DOX@H-MnO2-CHI-PEG as the dual-pH sensitive drug carrier system. For the drug carrier system, under the protection of mPEG, the carrier can be "invisible" under the normal physiological conditios (with a pH value being 7.4), so that non-specific phagocytosis of normal cells can be avoided, and circulation time of the carrier in vivo can be prolonged; while in a tumor tissue less-acidic environment (with the pH value being 6.5), the imine bond binding the mPEG to the CHI is hydrolytically cleaved, the mPEG as a protective layer falls off, and the positively charged CHI is exposed, so that acid activation is realized, uptake of tumorcells to the carrier is promoted, and the situation that the carrier enters cancer cells is facilitated; and under a more acid environment (with the pH value being 5.5) in the cancer cells, H-MnO2 can further degrade, so that the DOX is released to kill the cancer cells.

Description

technical field [0001] The invention belongs to the field of drug carriers, and in particular relates to a dual pH-sensitive drug carrier system and a preparation method thereof. Background technique [0002] In order to improve the defects in chemotherapy and improve the effectiveness of chemotherapy, drug delivery system (DDS) came into being. This is due to the fact that drug carrier systems can release drugs on-demand at specific sites in response to external or internal signals. For example, the drug carrier system includes redox, pH, light, enzyme single stimulus response, dual stimulus response or multiple different stimulus responses and other drug carrier systems. [0003] The use of pH response to construct drug carrier systems is the most widely used. Polymers that respond to pH generally contain weakly basic or weakly acidic functional groups. Weakly basic functional group - amino (-NH 2 ) can accept a proton and be positively charged under acidic conditions,...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K47/02A61K47/36A61K47/10A61K31/704A61P35/00
CPCA61K9/5115A61K9/5146A61K9/5161A61K31/704A61P35/00
Inventor 李草徐翔宇陈重银段军林刘畅江兵兵
Owner HUBEI UNIV
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