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An anti-tumor magnetic drug-loaded hybrid nanocapsule and its preparation method

A nanocapsule and anti-tumor technology, applied in the field of biomedical materials, can solve the problems of poor biocompatibility and poor control of drug release, and achieve highly selective and effective drug release and good photothermal response behavior , the effect of inhibiting multidrug resistance

Active Publication Date: 2021-06-01
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the existing nano-drug delivery system has poor biocompatibility, and the drug release cannot be well controlled. Therefore, it is important to study a stable, efficient, and biocompatible nano-drug delivery system for the treatment of tumors. significance

Method used

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  • An anti-tumor magnetic drug-loaded hybrid nanocapsule and its preparation method
  • An anti-tumor magnetic drug-loaded hybrid nanocapsule and its preparation method
  • An anti-tumor magnetic drug-loaded hybrid nanocapsule and its preparation method

Examples

Experimental program
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Effect test

Embodiment 1

[0065] Example 1 Fe 3 o 4 Preparation of -OA

[0066] in N 2 Under protective conditions, add Fe(acac) to the three-necked bottle 3 , 1,2-hexadecanediol, OA and oleylamine, and finally add dibenzyl ether. Use a sand bath to heat, wait until the temperature rises slowly to 200°C, keep it warm for 2 hours, then slowly raise the temperature to 265°C, hold it for 1 hour, then cool to room temperature. The reactant in the three-neck flask was transferred to the Erlenmeyer flask for magnetic separation. After the magnetic separation was completed, the supernatant was poured off, and a small amount of ethanol was added to transfer the black precipitate to a centrifuge tube for centrifugation (3000 r / min, 5 min). The supernatant obtained by centrifugation was discarded, a small amount of n-hexane was added dropwise, and the black precipitate was transferred to a high-speed centrifuge tube for centrifugation (8000r / min, 10min). Pipette the upper layer suspension into a conical fl...

Embodiment 2

[0067] Example 2 TPGS-Cystamine-NH 2 and HO-PEG-Cystamine-NH 2 preparation of

[0068] Weigh TPGS, succinic anhydride and DMAP in a round-bottomed flask, dissolve with anhydrous dichloromethane, and place in N 2 The reaction was carried out under anhydrous and oxygen-free conditions for 24 hours. After the reaction was completed, the reaction solution was filtered, and the filtrate was collected. In a dialysis bag (cut-off Mw=1KDa), dialyze with 50% ethanol for 48h, then dialyze in deionized water for 48h, and freeze-dry to obtain the product, which is called TPGS-COOH; wherein TPGS, succinic anhydride and DMAP The mass ratio is 7.69:1:1.31.

[0069] The TPGS-COOH obtained above, EDC·HCl, NHS and cystamine hydrochloride were dissolved in deionized water in a round bottom flask, and the pH was adjusted to 6-7, and then reacted for 48 hours under magnetic stirring. After the reaction was completed, it was dialyzed in deionized water for three days (cut-off Mw=1KDa), and fre...

Embodiment 3

[0072] Example 3 Preparation of Hep-TPGS-PEG-COOH

[0073] Sodium heparin, TPGS-Cystamine-NH 2 and HO-PEG-Cystamine-NH 2 Put it into a round bottom flask, then add EDC·HCl and NHS, mix well, then dissolve with deionized water, and adjust the pH of the solution to 6-7. After 48 hours of magnetic stirring reaction, the liquid was transferred to a dialysis bag (cut-off Mw=3500Da) and dialyzed with deionized water for 72 hours, and finally freeze-dried to obtain Hep-TPGS-PEG-OH. Among them, heparin sodium, TPGS-Cystamine-NH 2 , HO-PEG-Cystamine-NH 2 The mass ratio of , EDC·HCl and NHS is 4:1:1:2.24:1.36.

[0074] Put the Hep-TPGS-PEG-OH prepared above, succinic anhydride and DMAP in a round-bottomed branch bottle, dissolve with anhydrous DMF, react at room temperature under nitrogen protection for 24 hours, dialyze and freeze-dry to obtain PEG on the branched chain The heparin graft modification Hep-TPGS-PEG-COOH with -COOH at the end, wherein the mass ratio of Hep-TPGS-PEG-O...

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Abstract

The invention discloses an anti-tumor magnetic drug-loaded hybrid nanocapsule and a preparation method thereof. The preparation method comprises the following steps: firstly preparing magnetic ferric iron tetroxide nanoparticles (Fe 3 o 4 ‑OA), after modifying heparin sodium by condensation reaction with TPGS and PEG, and then using phacoemulsification to obtain Fe-encapsulated 3 o 4 ‑OA and doxorubicin magnetic nanocapsules, and then modify the tumor penetrating peptide iRGD on the periphery of the capsule to endow it with tumor cell targeting function, and finally treat it with ammonium bicarbonate to form a magnetic drug-loaded hybrid nanocapsule. The magnetic drug-loaded hybrid nanocapsules prepared by this method have strong targeting, good stimuli-response performance under near-infrared laser irradiation, and can generate carbon dioxide gas to achieve high-selective and rapid drug release at tumor sites. Good compatibility, high safety, and certain magnetic response behavior.

Description

technical field [0001] The invention belongs to the technical field of biomedical materials, and in particular relates to an anti-tumor magnetic drug-loaded hybrid nanocapsule and a preparation method thereof. Background technique [0002] Malignant tumors seriously threaten human life and health. As a fatal and major malignant disease, due to its complex pathogenesis and disease progression, it also has the characteristics of easy transfer and high abnormal proliferation, which has caused more than one million deaths worldwide every year. The incidence of malignant tumors continues to rise, which greatly affects the healthy life of residents, and also brings a heavy economic burden to families and society. Therefore, tumor treatment is an urgent medical and social problem to be solved. Common treatments for tumors include surgery, radiation therapy, and chemotherapy. Among them, chemotherapy is a commonly used method in the clinical treatment of tumors today. Its treatme...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/51A61K47/02A61K47/42A61K47/36A61K47/22A61K47/04A61K31/704A61K41/00A61P35/00
CPCA61K9/5115A61K9/5146A61K9/5161A61K9/5169A61K31/704A61K41/0042A61P35/00A61K2300/00
Inventor 易强英康珂张宇佳马瑾
Owner SICHUAN UNIV
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