Inner-outer double layer stepwise stimulation response delivery nano-carrier, and preparation method and application thereof
A transmission carrier and stimuli-response technology, which is applied in the field of inner and outer double-layer stimuli-response nano-transmission carriers and its preparation, can solve the problems of early release of loaded drugs, low drug bioavailability, and small amount of intracellular drug release, and achieve improved The effect of drug bioavailability, good water dispersibility and good biocompatibility
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Embodiment 1
[0044] (1) Dissolve 1.0g CTAB (cetyltrimethylammonium bromide) in a mixed solution of 480mL water and 3.5mL 2.0mol / L NaOH, raise the temperature to 70°C, add dropwise 5.0mL (22mmol ) TEOS (tetraethyl orthosilicate), 0.25mL (1.1mmol) APTES (γ-aminopropyltriethoxysilane) and 2.0mL 1,3,5-trimethylbenzene, keeping the reaction temperature at 70°C, stirring vigorously Reaction 2h. After completion of the reaction, the precipitate was filtered, washed with methanol, and the obtained product was dispersed in 50 mL of ethanol-HCl solution (48 mL of absolute ethanol+2 mL of concentrated hydrochloric acid with a concentration of 37% (w / v) was mixed), and the mixture was vigorously heated at 80 ° C. Stir for 10 h, remove CTAB, finally filter the precipitate, and dry in vacuum to obtain aminated mesoporous silicon nanoparticles. Disperse 0.20g of aminated mesoporous silicon nanoparticles in an aqueous solution, add 0.05g of 3,3'-dithiodipropionic acid and 0.04g of EDC, react at room temp...
Embodiment 2
[0049] (1) As a reference, an equivalent amount of succinic anhydride was used to replace 3,3'-dithiodipropionic acid, and other steps were the same as step (1) in Example 1 to prepare nanoparticles without disulfide bonds.
[0050] (2) Add 0.20 g of nanoparticles without disulfide bonds to 5 ml of PBS solution (pH 7.4) containing 0.02 g of doxorubicin hydrochloride, and stir for 24 hours to fully adsorb the doxorubicin to the mesoporous silicon nanoparticles , then add 0.10g PEI to the nanoparticle dispersion loaded with doxorubicin, then add 0.05g EDC and 0.03g NHS to catalyze the reaction. After the reaction is complete, centrifuge at 10,000 rpm for 5 minutes to remove ungrafted polymers. The product is freeze-dried to obtain the PEI / mesoporous silicon nanocarrier loaded with doxorubicin.
[0051] (3) Dissolve 0.05g of 2,3-dimethylmaleic anhydride in 10ml of DMSO, add 0.20g of PEI / mesoporous silicon nanocarrier loaded with doxorubicin, and react for 24h under nitrogen prot...
Embodiment 3
[0053] (1) The preparation process is the same as step (1) of Example 1 to obtain nanoparticles containing disulfide bonds.
[0054] (2) The second-generation polyamide-amine dendrimer (PAMAM) was prepared according to the method reported in the literature [Mesoporous siliconanoparticles with controlled loading of cationic dendrimer for gene delivery. Materials Research Express, 2014, 1:035403.].
[0055] (3) Add 0.20 g of nanoparticles containing disulfide bonds to 5 ml of PBS solution (pH 7.4) containing 0.02 g of doxorubicin hydrochloride, and stir for 24 hours to fully absorb the doxorubicin into the mesoporous silicon nanoparticles , and then add 0.10g PAMAM to the doxorubicin-loaded nanoparticle dispersion, then add 0.05g EDC and 0.03g NHS to catalyze the reaction. After the reaction is complete, centrifuge at 10,000 rpm for 5 minutes to remove ungrafted polymers. The product is freeze-dried to obtain the PAMAM / mesoporous silicon nanocarrier loaded with doxorubicin.
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