Cholesterol-modified biodegradable polycation carrier as well as preparation method and application thereof
A technology of polycation and cholesterol, which is applied to medical preparations with non-active ingredients, medical preparations containing active ingredients, and pharmaceutical formulas, etc., can solve the problems of low transfection efficiency and toxicity, and achieve high gene transfer efficiency and biological Good compatibility and low cytotoxicity
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Embodiment 1
[0046] Example 1 Synthesis of cholesterol-modified (quaternary bromide linkage) polyamide-amine
[0047] Synthesis of rPAA Precisely measure two commercially available monomers N,N'-dimethyldipropylenetriamine (DMDPTA) and N,N'-bis(acryloyl)cystamine (CBA) in equal molar ratio, Dissolve in an appropriate amount of methanol and water mixed solvent, the concentration of each monomer is 2mmol / 3.5mL, and react for 3 days in the dark under the protection of argon at 37℃. After the reaction solution becomes viscous, add excess ( 10mol%) DMDPTA continued to react for 2 days, the product was dialyzed with absolute ethanol (molecular weight cutoff 3.5KDa), the ethanol solvent was removed by rotary evaporation, the product was vacuum dried for 24 hours, and finally polyamide-amine cationic polymer (rPAA) was obtained ( figure 1 ).
[0048] Synthesis of Cholesterol Bromide (CH-Br) The synthesis of this substance used the method reported in the literature (Nat Mater 2006; 5: 791-796, Biomater...
Embodiment 2
[0050] Example 2 Synthesis of cholesterol-modified polyamide-amine (rPAA-Ch) (directly connected by amide bond)
[0051] The synthesis of P(CBA-DMDPTA) polymer is precisely measured in equimolar ratio of two commercially available monomers N,N'-dimethyldipropylenetriamine (DMDPTA) and N,N'-bis(acryloyl) ) Cystyamine (CBA), dissolved in an appropriate amount of methanol and water mixed solvent, the concentration of each monomer is 2mmol / 3.5mL, under the protection of argon at 37℃, the reaction is protected from light for 3 days until the reaction solution becomes viscous After thickening, add excess (10mol%) DMDPTA to continue the reaction for 2 days. The product is dialyzed with absolute ethanol (with a molecular weight cutoff of 3.5KDa), the ethanol solvent is removed by rotary evaporation, and the product is vacuum dried for 24 hours to finally obtain a polyamide-amine polymer ( rPAA).
[0052] Synthesis of cholesterol-modified (amide bond directly connected) polyamide-amine (rP...
Embodiment 3
[0053] Example 3 Evaluation of physical and chemical properties of rPAA-Ch polymer in vitro
[0054] Measurement of Critical Micelle Concentration (CMC) This example illustrates the measurement of the critical micelle concentration (CMC) of cholesterol-modified rPAA of the present invention. According to the reference (Biomaterials2007; 28: 4132-42.), the CMC of the polymer was measured by the fluorescent probe method. In short, add an equal volume of pyrene acetone solution to 10mL glass tubes in sequence. After the acetone volatilizes, add 6mL polymer solutions of different concentrations (0.01-1000μg / mL) to each tube. The final concentration of pyrene is 6.0× 10 -7 M. The polymer aqueous solution was sonicated in a bath at 37°C for 2 hours under dark conditions, and then shaken on a shaker at 37°C for 20 hours. A fluorescence spectrophotometer was used to measure the fluorescence spectrum of the solution, the fixed scattering wavelength was 395nm, the slit width was 5nm, the...
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