Method for preparing oxidation reduction sensitive nanometer targeting carriers

A targeting and carrier technology, applied in the fields of biomedicine and nanomaterials, can solve the problems of poor drug loading and controlled release efficiency, low active targeting performance, etc., achieving strong targeting, improving tumor treatment effect, and high application Foreground effect

Active Publication Date: 2015-12-23
HARBIN INST OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The purpose of the present invention is to provide a combination of organic-inorganic drug-loaded matrix for the current problems of low active targeting performance of tumor vectors, non-degradable in vivo deposition leading to adverse reactions, and low drug-loaded controlled release efficiency. , preparation method of redox-sensitive nano-targeting carrier highly sensitive to pH value and reducing environment of tumor cells

Method used

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  • Method for preparing oxidation reduction sensitive nanometer targeting carriers

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Embodiment 1

[0034] This embodiment prepares the GCP-SS-R of loading doxorubicin hydrochloride (DOX) according to the following steps:

[0035] a. Take 10mL of 0.3moL / L CaCl 2 The solution was added to 200 mL of the oil phase. The composition of the oil phase: cyclohexane / polyoxyethylene (5) nonylphenyl ether is 80 / 30 (v / v). Another 10mL15mmoL / LNa 2 HPO 3 Solution and 5mL of DOPA chloroform solution with a concentration of 30mmol / L were added to another part of the above oil phase. The two phases were mixed and stirred for 2h. Add 100 mL of ethanol, centrifuge at 10,000 rpm for 30 min, remove the upper layer of cyclohexane and surfactant, wash with ethanol three times, and freeze-dry to obtain CaP particles.

[0036] b. Take 100mg of CaP microparticles and add 10ml of deionized water. Take another 100mg of modified and activated chitosan and 10mgDOX and dissolve them in 50mL of DMSO. Slowly drop the CaP emulsion into the chitosan solution, stir continuously at 25°C, and react for 8 ho...

Embodiment 2

[0041]This embodiment prepares PCP-SS-T loaded with siRNA according to the following steps:

[0042] a. Prepare CaP microparticles according to step a of Example 1.

[0043] b. Take 10 mg of CaP microparticles and add 5 ml of deionized water, and another 10 mg of modified and activated PEI and 100 μg of siRNA are dissolved in 10 mL of DMSO. The CaP emulsion is slowly dropped into the PEI solution, stirred continuously at 25 °C for 8 h, centrifuged at 10,000 rpm for 30 min, and discarded. The supernatant was freeze-dried to obtain siRNA-loaded PCP microparticles.

[0044] c. Transfer 10 mg of PCP microparticles to 10 mL of MSDS solution with a concentration of 5 mg / mL, and slowly add 2 mL (10% concentration, m / v) of EDC·HCl aqueous solution and 2 mL (10% concentration, m / v) of NHS , reacted at room temperature, added 10 mg PAsp (MEA), stirred continuously, and reacted for 48 hours at 40° C. under nitrogen protection, and assembled the controlled release element on the drug-loa...

Embodiment 3

[0048] This embodiment prepares the PCP-SS-T of loading DOX and siRNA according to the following steps:

[0049] a. Prepare CaP microparticles according to step a of Example 1.

[0050] b. Take 10mg of CaP microparticles and add 5ml of deionized water, take another 10mg of modified and activated PEI-CS copolymer and dissolve it in 10mL of DMSO, add 100μg of siRNA and 1mgDOX, and slowly drop the CaP emulsion into the PEI-CS solution at 25°C Stir continuously for 8 hours under the conditions, centrifuge at 10,000 rpm for 30 minutes, discard the supernatant, and freeze-dry to obtain PCCP particles loaded with siRNA and DOX.

[0051] c. Transfer 10 mg of PCCP microparticles to 10 mL of MSDS solution with a concentration of 5 mg / mL, and slowly add 2 mL (10% concentration, m / v) of EDC·HCl aqueous solution and 2 mL (10% concentration, m / v) of NHS , react at room temperature, add 10mg of cystamine dihydrochloride, stir constantly, react for 6h under nitrogen protection at 40°C, and a...

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Abstract

The invention discloses a method for preparing oxidation reduction sensitive nanometer targeting carriers, and belongs to the technical field of biomedicine and nanometer materials. By the aid of the method, problems of poor active targeting performance, deposition and adverse reaction due to in-vivo non-degradation, low carried medicine release control efficiency and the like of existing tumor carriers can be solved. The method is used for preparing the organic-inorganic medicine carrying matrix combined oxidation reduction sensitive nanometer targeting carriers with high sensitivity to pH (potential of hydrogen) value of tumor cells and reducible environments. The method includes synthesizing calcium phosphate particles by the aid of micro-emulsion technologies and coating a layer of degradable organic macromolecular substances on the surface of each particle to form a medicine carrying core; assembling reducible environment sensitive cross-linking elements onto the medicine carrying cores, then grafting modified targeting factors and ultimately synthesizing the intelligent targeting nanometer micro-sphere carriers. The method has the advantages that the micro-sphere carriers have powerful targeting functions and are intelligent in medicine release control, stable in structure and free of toxic and side effects, and the like.

Description

technical field [0001] The invention belongs to the technical field of biomedicine and nanometer materials, and relates to a preparation method of redox sensitive degradable nano microsphere carrier. Background technique [0002] In recent years, research on improving the transfer efficiency of anticancer drug carriers has become a hot spot. The main research direction is to integrate multiple functions into the same carrier to achieve multi-factor targeting, compound drug loading and controlled drug release. New ideas in the design of carrier drug-loading elements, targeting guidance methods, drug release strategies, etc. continue to emerge, and the construction of new high-efficiency multifunctional nanocarriers is increasingly favored by researchers. [0003] Smart drug carriers are generally composed of a drug-loaded matrix connected with an environment-sensitive group and a drug. Selecting degradable materials, such as polyamino acid, chitosan, etc. as the drug-loading...

Claims

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Application Information

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IPC IPC(8): A61K9/19A61K31/704A61K48/00A61K47/42A61K47/18A61K47/20A61P35/00
Inventor 贺金梅颜廷胜李大龙
Owner HARBIN INST OF TECH
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