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Tumor specifically-enriched nanometer drug delivery system and preparation method thereof

An active and drug-based technology, applied in the field of amphiphilic block copolymers, can solve the problem of insufficient specific enrichment of drug transport and achieve high drug loading efficiency

Active Publication Date: 2017-08-01
BEIJING UNIV OF CHEM TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, most of these studies only focus on the drug release and delivery process of the nano-drug delivery system in tumor tissues or tumor cells, and pay little attention to the drug transport in the blood and the specific enrichment in tumors.

Method used

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  • Tumor specifically-enriched nanometer drug delivery system and preparation method thereof
  • Tumor specifically-enriched nanometer drug delivery system and preparation method thereof
  • Tumor specifically-enriched nanometer drug delivery system and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0161] PEG 5k -b-PBHMAGG 9k -b-P(HPMA-co-MAGG-co-AzMA) 60k -SC(=S)S(CH 2 ) 11 CH 3 preparation of

[0162] Synthetic route such as figure 1 shown.

[0163] (1) Dissolve 10 g of hydroxyl and methyl-terminated PEG with a number average molecular weight of 5000 in 40 mL of toluene, and after azeotropic water removal twice with toluene, add 4-dodecyltrithiocarbonate-4-carbonitrile 3.23 g of valeric acid and 0.1 g of DMAP were dissolved in 70 ml of toluene, and after complete dissolution, 1.98 g of DCC was added and reacted for 90 hours under stirring at room temperature. After the reaction, remove cyclohexyl urea (DCU) by suction filtration, then pour the filtrate into excess ether, collect the precipitate, dissolve the obtained precipitate in a small amount of toluene, and then precipitate with ether, repeat this 3-5 times until the ether is colorless. The precipitate was vacuum-dried at 40° C. for 24 hours, and the obtained product was a macromolecular chain transfer age...

Embodiment 2

[0168] PEG 5k -b-PBHMAGG 9k -b-P(HPMA-co-MAGG-co-AzMA) 30k -SC(=S)S(CH 2 ) 11 CH 3 preparation of

[0169] Using the same reaction route and reaction conditions as in Example 1, the addition of HPMA, MAGG and AzMA was adjusted to 0.18g, 0.02g and 0.005g, and the title final product was prepared by polymerization.

[0170] Hereinafter, this polymer is simply referred to as P5-B9-H30.

Embodiment 3

[0172] PEG 5k -b-PBHMAGG 5k -b-P(HPMA-co-MAGG-co-AzMA) 60k -SC(=S)S(CH 2 ) 11 CH 3 preparation of

[0173] Using the same reaction route and reaction conditions as in Example 1, the amount of BHMAGG added was adjusted to 0.35 g, and the title final product was prepared by polymerization.

[0174] Hereinafter, this polymer is simply referred to as P5-B5-H60.

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PUM

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Abstract

The invention discloses a polymer, which has a narrow molecular weight distribution, which is less than 1.3, and has a general formula of B-z-H, P-B-H and P-H-B. In the general formula, B represents a block for bonding a drug, H represents a hydrophilic block, P represents a PEG block, and z represents having or not having environment-responsive chemical bond connection. The polymer forms a micelle with small particle size in water, the micelle can spontaneously aggregate to form an aggregation having a large particle size, and the aggregation has superior tumor specific enrichment than an ordinary drug carrier. The polymer has long body circulation time, and has the feature of being enriched on a tumor. The polymer can carry a drug through a covalent bond and / or a non-covalent bond, and the obtained product can further couple to a targeting molecule and / or a labelled molecule for preparing an administration system or a detection reagent.

Description

technical field [0001] The invention relates to an amphiphilic block copolymer containing PEG and / or PHPMA and its preparation method and application. The copolymer can be used as a drug carrier to form a polymer-drug conjugate with a drug, and is used in targeting especially The invention relates to a tumor-targeted drug delivery system and belongs to the technical field of pharmaceutical auxiliary materials. Background technique [0002] Tumor has always been a major disease that threatens human health. Traditional treatment methods have high mortality, low cure rate and poor prognosis. However, with the development of nanotechnology, nano-drug delivery systems can bring longer blood circulation time and lower systemic toxicity to anti-tumor drugs. It is a hot issue that is widely concerned by researchers (Collins I., NAT CHEM BIOL, 2006, 2:689-700). [0003] At present, a large number of new nano-drug delivery systems with different chemical structures or response capab...

Claims

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Application Information

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IPC IPC(8): C08F293/00C08F220/60C08F220/58A61K47/58A61K45/00A61K9/107A61K49/00A61P35/00A61K31/704
CPCA61K31/704A61K45/00A61K49/0032A61K49/0054A61K49/221C08F220/58C08F220/60C08F220/603C08F293/005C08F2438/03
Inventor 喻青松甘志华申童管书丽
Owner BEIJING UNIV OF CHEM TECH
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