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Simultaneous-delivery nanometer carrier and preparation method thereof

A nano-carrier and co-delivery technology, applied in the field of targeted drug delivery systems and nano-carriers, can solve the problems of limited ability to compress nucleic acids and small molecular weight, and achieve low cytotoxicity, good biocompatibility, and good biocompatibility Effect

Active Publication Date: 2015-09-16
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Small molecular polyamines are excellent carriers for gene delivery, but their molecular weight is small and their ability to compress nucleic acids is limited, so it is necessary to synthesize them into polymers

Method used

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  • Simultaneous-delivery nanometer carrier and preparation method thereof
  • Simultaneous-delivery nanometer carrier and preparation method thereof
  • Simultaneous-delivery nanometer carrier and preparation method thereof

Examples

Experimental program
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Embodiment 1

[0045] The pSPE synthesis scheme is as follows: Dissolve 1.2mmol of spermine (SPE) in 10mL of anhydrous methanol, dissolve 1mmol of polyethylene glycol diacrylate (PEGDA) in 10mL of anhydrous methanol, and then slowly add the PEGDA solution to the SPE solution, and then stirred at 40°C for 36h. The obtained product was dissolved in deionized water at 4°C, and then dialyzed at 4°C for 2d with a dialysis belt with a molecular weight cut-off of 5000. Finally, the product was freeze-dried and stored at -20°C to obtain pSPE.

Embodiment 2

[0047] Structural identification and molecular weight characterization of pSPE polymers

[0048] The structure of pSPE polymer was identified by proton nuclear magnetic and infrared, and the molecular weight was detected by gel retardation chromatography.

Embodiment 3

[0050] PLGA-pSPE synthesis: take an appropriate amount of PLGA-COOH (molecular weight 10k) 1mmol, dissolve it in 10mL anhydrous DMSO, add DCC and NHS, stir at room temperature for 0.5-24h, centrifuge to remove the precipitate, supernatant and 10mL containing 1.2mmol pSPE Anhydrous DMSO solution was mixed, stirred and reacted at room temperature for 12 hours, and dialyzed at 4°C for 2 days with a dialysis bag with a molecular weight cut-off value of 10,000 to obtain PLGA-pSPE.

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Abstract

The invention discloses a nanometer carrier for simultaneous delivery of medicines and genes and a preparation method of the nanometer carrier, and particularly relates to a simultaneous-delivery nanometer carrier PLGA-pSPE (polyspermine)-PEG (polyethylene glycol)-Ligand capable of simultaneously loading medicines and genes. The medicine delivery system is realized by the following steps: synthesizing pSPE with spermine at two ends by using spermine and polyethylene glycol acrylate (PEGDA) through Michael addition reaction; generating amphipathic PLGA-pSPE from a pSPE and poly(lactide-co-glycolide) copolymer PLGA through condensation reaction of amino and carboxyl; and generating PLGA-pSPE-PEG-Ligand by using PLGA-pSPE and PEG (HOOC-PEG-Ligand) of which one end is provided with carboxyl and the other end is connected with a target head through condensation reaction of amino and carboxyl, and self-assembling to form nano particles, wherein kernel PLGA is capable of well loading insoluble medicines as a hydrophobic material; the pSPE contains a lot of secondary amino groups, is positively charged, is capable of well loading negatively charged genes and grafting an invisible material PEG with the target head; relatively good target medicine delivery can be realized under the combined action of the PEG and the target head; and the medicines and the genes are delivered to the same target cell.

Description

technical field [0001] The present invention relates to a nano-carrier for co-delivery of drugs and genes, in particular to a targeted drug delivery system that simultaneously loads genes and therapeutic drugs. The drug delivery system of the present invention can target target cells and deliver genes and drugs into cells The action site achieves the purpose of synergistic treatment and belongs to the technical field of pharmaceutical preparations. Background technique [0002] Drugs and genes are co-encapsulated by polymer nanocarriers and delivered to target cells. On the one hand, drugs are slowly released, and on the other hand, therapeutic genes are expressed to achieve mutual promotion. The synergistic effect of drug therapy and gene therapy can be realized, thereby It is an ideal method for treating malignant diseases such as tumors to increase curative effect. [0003] Small molecule polyamine is an excellent carrier for gene delivery, but its molecular weight is sm...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/34A61K48/00A61P35/00C08G81/00
Inventor 姜虎林乔建斌邢磊
Owner CHINA PHARM UNIV
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