Nano medicine delivery system for photo-thermal chemotherapy combined therapy and preparation method

A nano-drug delivery system and combined therapy technology, which is applied in the direction of pharmaceutical formulations, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., can solve the problems of limiting ICG application and instability, and achieve simple synthesis methods Ease of application, wide application, and strong antitumor activity

Inactive Publication Date: 2018-09-04
CHONGQING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, ICG is very unstable in aqueous solution and is easily cleared quickly in the blood circulation, and it is easy to form dimers between molecules, resulting in fluorescence quenching. [5]
These deficiencies seriously limit the application of ICG in tumor diagnosis and treatment.

Method used

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  • Nano medicine delivery system for photo-thermal chemotherapy combined therapy and preparation method
  • Nano medicine delivery system for photo-thermal chemotherapy combined therapy and preparation method
  • Nano medicine delivery system for photo-thermal chemotherapy combined therapy and preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Copolymer preparation

[0036] Materials and Methods:

[0037] Propylene sulfide, purchased from TCI company, 2-bromo-2-methylpropionyl bromide, sodium methoxide methanol solution purchased from Bailingwei company, N-isopropylacrylamide, N,N-dimethylacrylamide purchased from Adamas company , Adriamycin was purchased from Anaiji Company, and indocyanine green was purchased from Macleans Company. The solvents used in the reaction were all re-evaporated to remove water and dried.

[0038] 1. Synthesis of polypropylene sulfide macroinitiator, its steps are:

[0039] Synthesized by anionic ring-opening polymerization method to prepare polypropylene sulfide. 20mL of dry tetrahydrofuran was introduced into nitrogen for 1h, then 2mL of TBP, 162mg of 2-hydroxyacetyl thioester, 2.8mL of sodium methoxide methanol solution were added to react for a few minutes, 1g of episulfide propene was added, and then reacted for a while, 0.6mL of bromoacetamide was added, React for 2 hours, spin off...

Embodiment 2

[0043] Preparation of drug-loaded micelles

[0044] Weigh 5mg DOX, 5mg ICG, and 10mg copolymer respectively, add appropriate amount of DMF to dissolve. Under constant stirring, slowly add to 10mL of water, continue to stir for 8h, and then dialyze to remove DMF solvent. After dialysis, the product is filtered through a 0.22μm microporous membrane for sterilization. The prepared micelles are named DIMs. In addition, micelles containing only DOX and only ICG were prepared according to the same method and named DMs and IMs, respectively.

Embodiment 3

[0046] Photothermal experiment determination of drug-loaded micelles

[0047] Take 0.5mL of H 2 O, 5 and 20μg / mL ICG solution, 5 and 20μg / mL drug-loaded micelle solution, irradiate under 808nm near infrared light for 15min, and record the temperature change with a temperature recorder, such as image 3 As shown,

[0048] It can be seen that the maximum temperature of drug-loaded micelles is higher than that of LCST, which can cause the phase change of micelles.

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Abstract

The invention provides a nano medicine delivery system for photo-thermal chemotherapy combined therapy and a preparation method. The nano medicine delivery system is medicine carrying micelle, whereinthe medicine carrying micelle is prepared by enabling poly-propylene sulfide-b-poly(N-isopropyl acrylamide-co-N,N-dimethacrylamide) of formula (I) as shown in the specification to polymerize by self,and by coating doxorubicin (DOX) and indocyanine green (IGG) in micelle. The nano medicine delivery system is characterized in that under radiation of near-infrared light of 808nm, because of photo-thermal effects of the indocyanine green, a temperature can be increased, a hydrophilic layer on the surface of the micelle can be turned into a hydrophobic layer, and the uptake of tumor cells upon the medicine carrying micelle can be improved; meanwhile, the medicine carrying micelle can be oxidized by singlet oxygen generated from the indocyanine green in lighting, and thus medicine release canbe promoted. The nano medicine delivery system has the characteristics of dual responsiveness, combined therapy under near-infrared lighting, and good anti-tumor activity.

Description

Technical field [0001] The invention belongs to the technical field of tumor targeting and controlled-release drug delivery, and relates to a nano-drug delivery system made of a polymer based on temperature and oxidation dual response, and in particular to a photothermal chemotherapy that can be irradiated with near-infrared light Drug-loaded micelles for combination therapy and preparation methods thereof. Background technique [0002] Tumors have become one of the most serious diseases threatening human health. Commonly used clinical cancer treatment methods include chemotherapy, radiotherapy and surgical treatment, among which chemotherapy is the most commonly used and important treatment approach. However, the anti-tumor drugs used clinically have many defects in the application, such as: poor stability of water-soluble agents, large toxic side effects of drugs, and killing normal cells of the human body while treating diseases. The drug delivery system and controlled relea...

Claims

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Application Information

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IPC IPC(8): A61K9/107A61K47/32A61K41/00A61K47/69A61K47/58A61K31/704A61P35/00
Inventor 胡平郑强唐庆贺耘
Owner CHONGQING UNIV
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