Multifunctional nano-medicinal composition, as well as preparation method and application thereof

Abstract

The invention provides a multifunctional nano-medicinal composition, as well as a preparation method and application thereof. The composition comprises a carrier and an active ingredient loaded on the carrier, wherein the carrier is nano-particles which are prepared by adsorbing polydopamine to the nano-micelle surface form by poly(2-methyl-2-acrylic acid-2-(2-methoxyethoxy-ethyl-co-oligo(ethylene glycol) methyl ether methacrylate-co-dimethylaminoethyl methacrylate-poly(lactate-co-glycolic acid) segmented copolymer; the active ingredient comprises a hydrophobic drug and hydrophilic drug. The multifunctional nano-medicinal composition has a size of 50-1000nm, and has a drug constant-release effect, can be combined with chemotherapy to improve the treatment efficiency since polydopamine has a photothermal therapy effect, and can be applied to tumor treatment medicines.

Description

technical field

[0001] The invention belongs to the field of nano-biomedicine, and in particular relates to a multifunctional nano-medicine composition and a preparation method and application thereof. Background technique

[0002] Nano-drug delivery system refers to the drug delivery system formed by drugs and nano-carriers with a particle size ranging from 1-1000nm, including nanospheres, nanocapsules, nanoparticles and nanoliposomes. Compared with other drug carriers, the nano-drug delivery system has significant advantages: (1) ultra-small volume, which can pass through the smallest capillaries in the human body, and is not easily cleared by phagocytic cells, prolonging the residence time in the circulatory system; (2) ) reach target sites such as the liver, spleen, lung, bone marrow, and lymph where the reticuloendothelial system is concentrated; (3) can penetrate the interstitial space and be absorbed by cells, which is conducive to transdermal absorption and intracell...

Examples

Embodiment 1

[0044] 20mg of P(MEO 2 MA-co-OEGMA-co-DMAEMA)-b-PLGA) was dissolved in 1mL of dichloromethane, 0.2mL of doxorubicin hydrochloride aqueous solution (7.5mg / mL) was added, after mixing, it was sonicated for 3min, and then 2mL of 2% mass concentration was added Vortex and mix well, add 0.2mL of docetaxel (5mg / mL) dissolved in dichloromethane, and after ultrasonic emulsification for 8min, slowly add the mixture into 10mL of 0.3% polyvinyl alcohol and stir 10min. Evaporate under reduced pressure with a rotary evaporator to remove dichloromethane in the solution, centrifuge at 13,000 rpm for 10 min, then centrifuge with deionized water, and wash. 100 mg of the above-obtained nanomicelles (ie, the result after washing) were added to a Tris buffer solution with a pH of 8.5, and the concentration of Tris after the addition was 10 mmol / L. Add 50 mg of dopamine, react for 24 hours, and centrifuge at 60,000 rpm to obtain a multifunctional nano drug composition. Among them, P(MEO 2 The ...

Embodiment 2

[0046] 20mg of P(MEO 2 MA-co-OEGMA-co-DMAEMA)-b-PLGA) was dissolved in 1 mL of dichloromethane, 0.2 mL of doxorubicin hydrochloride aqueous solution (5 mg / mL) was added, after mixing, it was sonicated for 5 min, and then 10 mL of 2% mass concentration was added Aqueous polyvinyl alcohol solution, vortex and mix evenly, add 0.2mL of docetaxel (5mg / mL) dissolved in dichloromethane, then ultrasonic emulsification for 8min, evaporate under reduced pressure with a rotary evaporator to remove dichloromethane in the solution Afterwards, centrifuge at 13000rpm for 10min, and then wash with deionized water. 100 mg of the nanomicelles obtained above (ie, the product after washing) were added to a Tris buffer solution with a pH of 7.5, and the concentration of Tris after addition was 1 mmol / L. Add 10 mg of dopamine, react for 4 hours, and centrifuge at 10,000 rpm to obtain a multifunctional nanomedicine composition. Among them, P(MEO 2 The weight-average molecular weight of MA-co-OEGM...

Embodiment 3

[0048] 20mg of P(MEO 2 MA-co-OEGMA-co-DMAEMA)-b-PLGA) was dissolved in 1mL of ethyl acetate, 0.2mL of doxorubicin hydrochloride aqueous solution (5mg / mL) was added, after mixing, it was sonicated for 5min, and then 10mL of 2% mass concentration Polyvinyl alcohol and 10 mL of propylene glycol block polyether F68 aqueous solution with a mass concentration of 2% were mixed evenly by vortexing, and 0.2 mL of docetaxel (1 mg / mL) dissolved in dichloromethane was added, and after ultrasonic emulsification for 8 min, the solution was evaporated by rotary evaporation After vacuum evaporation and removal of dichloromethane in the solution, centrifuge at 13,000 rpm for 10 min, and then centrifuge and wash with deionized water. 10 mg of the nanomicelles obtained above (ie, the result after washing) were added to a Tris buffer solution with a pH of 10.5, and the concentration of Tris after the addition was 20 mmol / L. Then add 100 mg of dopamine, react for 48 hours, and then centrifuge at ...

technical field

[0001] The invention belongs to the field of nano-biomedicine, and in particular relates to a multifunctional nano-medicine composition and a preparation method and application thereof. Background technique

[0002] Nano-drug delivery system refers to the drug delivery system formed by drugs and nano-carriers with a particle size ranging from 1-1000nm, including nanospheres, nanocapsules, nanoparticles and nanoliposomes. Compared with other drug carriers, the nano-drug delivery system has significant advantages: (1) ultra-small volume, which can pass through the smallest capillaries in the human body, and is not easily cleared by phagocytic cells, prolonging the residence time in the circulatory system; (2) ) reach target sites such as the liver, spleen, lung, bone marrow, and lymph where the reticuloendothelial system is concentrated; (3) can penetrate the interstitial space and be absorbed by cells, which is conducive to transdermal absorption and intracell...

Examples

Embodiment 1

[0044] 20mg of P(MEO 2 MA-co-OEGMA-co-DMAEMA)-b-PLGA) was dissolved in 1mL of dichloromethane, 0.2mL of doxorubicin hydrochloride aqueous solution (7.5mg / mL) was added, after mixing, it was sonicated for 3min, and then 2mL of 2% mass concentration was added Vortex and mix well, add 0.2mL of docetaxel (5mg / mL) dissolved in dichloromethane, and after ultrasonic emulsification for 8min, slowly add the mixture into 10mL of 0.3% polyvinyl alcohol and stir 10min. Evaporate under reduced pressure with a rotary evaporator to remove dichloromethane in the solution, centrifuge at 13,000 rpm for 10 min, then centrifuge with deionized water, and wash. 100 mg of the above-obtained nanomicelles (ie, the result after washing) were added to a Tris buffer solution with a pH of 8.5, and the concentration of Tris after the addition was 10 mmol / L. Add 50 mg of dopamine, react for 24 hours, and centrifuge at 60,000 rpm to obtain a multifunctional nano drug composition. Among them, P(MEO 2 The ...

Embodiment 2

[0046] 20mg of P(MEO 2 MA-co-OEGMA-co-DMAEMA)-b-PLGA) was dissolved in 1 mL of dichloromethane, 0.2 mL of doxorubicin hydrochloride aqueous solution (5 mg / mL) was added, after mixing, it was sonicated for 5 min, and then 10 mL of 2% mass concentration was added Aqueous polyvinyl alcohol solution, vortex and mix evenly, add 0.2mL of docetaxel (5mg / mL) dissolved in dichloromethane, then ultrasonic emulsification for 8min, evaporate under reduced pressure with a rotary evaporator to remove dichloromethane in the solution Afterwards, centrifuge at 13000rpm for 10min, and then wash with deionized water. 100 mg of the nanomicelles obtained above (ie, the product after washing) were added to a Tris buffer solution with a pH of 7.5, and the concentration of Tris after addition was 1 mmol / L. Add 10 mg of dopamine, react for 4 hours, and centrifuge at 10,000 rpm to obtain a multifunctional nanomedicine composition. Among them, P(MEO 2 The weight-average molecular weight of MA-co-OEGM...

Embodiment 3

[0048] 20mg of P(MEO 2 MA-co-OEGMA-co-DMAEMA)-b-PLGA) was dissolved in 1mL of ethyl acetate, 0.2mL of doxorubicin hydrochloride aqueous solution (5mg / mL) was added, after mixing, it was sonicated for 5min, and then 10mL of 2% mass concentration Polyvinyl alcohol and 10 mL of propylene glycol block polyether F68 aqueous solution with a mass concentration of 2% were mixed evenly by vortexing, and 0.2 mL of docetaxel (1 mg / mL) dissolved in dichloromethane was added, and after ultrasonic emulsification for 8 min, the solution was evaporated by rotary evaporation After vacuum evaporation and removal of dichloromethane in the solution, centrifuge at 13,000 rpm for 10 min, and then centrifuge and wash with deionized water. 10 mg of the nanomicelles obtained above (ie, the result after washing) were added to a Tris buffer solution with a pH of 10.5, and the concentration of Tris after the addition was 20 mmol / L. Then add 100 mg of dopamine, react for 48 hours, and then centrifuge at ...

Images