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Glutathione/pH double stimulus responsive ionic-crosslinked polymer nano-hydrogel, and preparation method and applications thereof

A dual stimuli-responsive, nano-hydrogel technology, applied in the field of biomedicine, can solve the problems of low dose and human side effects, and achieve the effect of reducing side effects and clear and concise preparation process.

Inactive Publication Date: 2015-09-09
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the dose to reach the tumor tissue through the body fluid circulation after direct injection is very low, and it will bring serious side effects to the human body.

Method used

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  • Glutathione/pH double stimulus responsive ionic-crosslinked polymer nano-hydrogel, and preparation method and applications thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Embodiment 1: the preparation of zinc cross-linked PMAA nano hydrogel

[0032] MAA monomer 400 mg, ZDMA crosslinker 100 mg, AIBN initiator 16.7 mg, acetonitrile 40 mL, heated to 95 o C, reflux the solvent for 2 hours, centrifuge to remove the solvent and unreacted monomer, wash with ethanol and deionized water 3 times, and dry in a vacuum oven for 24 hours.

Embodiment 2

[0033] Embodiment 2: Preparation of zinc crosslinked PAA nano hydrogel

[0034] AA monomer 400 mg, ZDMA crosslinker 100 mg, BPO initiator 15.3 mg, 40 mL acetonitrile-ethanol mixed solvent (V acetonitrile: V ethanol = 1:1), heated to 95 o C. Refluxing the solvent for 2 hours, centrifuging to remove the solvent and unreacted monomers, washing with acetone and deionized water three times, and drying in a vacuum oven for 24 hours.

Embodiment 3

[0035] Embodiment 3: the preparation of zinc cross-linked PMAA-co-PHPMA nano hydrogel

[0036] 200 mg of MAA monomer, 200 mg of HPMA, 100 mg of ZDMA crosslinker, 16.7 mg of AIBN initiator, 40 mL of acetonitrile-toluene mixed solvent (V acetonitrile: V toluene = 4: 1), heated to 95 o C. Refluxing the solvent for 2 hours, centrifuging to remove the solvent and unreacted monomers, washing with acetone and deionized water three times, and drying in a vacuum oven for 24 hours.

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Abstract

The invention belongs to the technical field of biological medicine, and specifically relates to a glutathione / pH double stimulus responsive ionic-crosslinked polymer nano-hydrogel, a preparation method thereof, and applications of the glutathione / pH double stimulus responsive ionic-crosslinked polymer nano-hydrogel as a drug carrier. According to the preparation method, methacrylic acid, acrylic acid, and acrylamide are taken as monomers; zinc dimethacrylate and calcium dimethacrylate are taken as cross-linking agents; and refluxing precipitation is carried out in acetonitrile solvent so as to prepare a nano-hydrogel with high uniformity and low dispersity; and then a folate-targeted polyethylene glycol-modified nano-hydrogel is obtained via reaction of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride / N-hydroxy succinimide with polyethylene glycol-folic acid molecules which are modified via amination. The glutathione / pH double stimulus responsive ionic-crosslinked polymer nano-hydrogel shapes like balls with regular morphology, is uniform in size, possesses glutathione and pH double stimulus responsiveness; particle size can be adjusted; no obvious deposition is observed after long-term uniform dispersion in water; colloidal stability and dispersibility are excellent; and the glutathione / pH double stimulus responsive ionic-crosslinked polymer nano-hydrogel is an ideal drug carrier.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a nano hydrogel and a preparation method and application thereof. Specifically, it is an ion-crosslinked nanometer hydrogel with glutathione / pH dual stimulus responsiveness, its preparation method and its application as a drug carrier. Background technique [0002] According to a large number of studies, doxorubicin is an effective anticancer drug, which can inhibit the synthesis of RNA and DNA, has the strongest inhibitory effect on RNA, has a wide antitumor spectrum, and can kill tumor cells in various growth cycles. Killing effect. However, the dose to reach the tumor tissue through body fluid circulation after direct injection is very low, and it will bring serious side effects to the human body. There have been many studies in the world to develop target-targeted drug delivery systems (drug delivery systems, DDS) to enhance drug efficacy and reduce side eff...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08G81/02C08F220/06C08F222/02C08F220/58C08F220/28C08G65/48A61K31/704A61P35/00A61K47/30
Inventor 张子豪汪长春
Owner FUDAN UNIV
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