Nanometer drug complex loaded with paclitaxel and preparation method thereof

Abstract

The invention provides a nanometer drug complex loaded with paclitaxel. The nanometer drug complex comprises paclitaxel and a nanometer drug carrier, wherein the nanometer drug carrier is graphene oxide modified by amino polyethylene glycol. The invention also provides a preparation method for the nanometer drug complex loaded with paclitaxel. The method comprises the following steps: amino polyethylene glycol is modified on the surface of graphene oxide via an amide covalent bond so as to obtain the nanometer drug carrier, and paclitaxel is absorbed via pi-pi interaction so as to obtain the nanometer drug complex. The preparation method for the nanometer drug complex provided by the invention is simple and feasible, has low cost and solves the problems of great toxic and side effects and complex formulation preparation in conventional paclitaxel formulations using polyoxyethylene castor oil as a cosolvent; and the nanometer drug complex has good water-solubility, stability and biological compatibility, small toxic and side effects and good safety and is capable of effectively killing tumor cells and improving therapeutic effects of paclitaxel.

Description

technical field

[0001] The invention belongs to the technical field of biomedicine, and in particular relates to a paclitaxel-loaded nano drug complex and a preparation method thereof. Background technique

[0002] Paclitaxel (PTX) is a natural antineoplastic drug, widely used in the treatment of ovarian cancer, breast cancer, lung cancer and other tumors. However, because PTX is poorly soluble in water, has low bioavailability, short half-life and high toxicity, it is necessary to develop a dosage form of paclitaxel clinically to improve its targeting effect on tumors.

[0003] The dosage forms of PTX in clinical application mainly include PTX injection and PTX liposome. However, the dosage form of paclitaxel injection needs to use a mixed solution of co-solvent polyoxyethylene castor oil and ethanol to increase the solubility of PTX. clinical application. And paclitaxel liposome, biocompatibility is good, has avoided the toxic side effect that solubilizing polyoxyethyle...

Examples

Embodiment 1

[0049] A preparation method of a nano drug complex loaded with paclitaxel, comprising the steps of:

[0050] (1) Preparation of nano drug carrier solution:

[0051] Take graphene oxide and carry out carboxylation treatment to obtain an aqueous solution (concentration of 1 mg / mL) of carboxylated graphene oxide (NGO-COOH), take 20 mL, add hydrochloric acid to adjust the pH to 5.6, and 8 mg of N-hydroxysuccinyl Add imine (NHS) and 10 mg of 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) into NGO-COOH, ultrasonically disperse for 5 min, add 100 mg of amino polydiimide Alcohol monomethyl ether (mPEG-NH 2 , molecular weight is 5000), at room temperature, carry out amidation reaction 12h under stirring condition, obtain the first reaction liquid, transfer the first reaction liquid to ultrafiltration centrifuge tube (molecular weight cut-off is 30kDa), centrifuge at 6000rpm at low speed for 30min first , wash with deionized water, repeat the above centrifugation and...

Embodiment 2

[0071] A preparation method of a nano drug complex loaded with paclitaxel, comprising the steps of:

[0072] (1) Preparation of nano drug carrier solution:

[0073] Take graphene oxide and carry out carboxylation treatment to obtain an aqueous solution (concentration of 1 mg / mL) of carboxylated graphene oxide (NGO-COOH), take 20 mL, add hydrochloric acid to adjust the pH to 5.6, and 8 mg of N-hydroxysuccinyl Add imine (NHS) and 10 mg of 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) into NGO-COOH, ultrasonically disperse for 20 min, add 20 mg of amino polydiimide Alcohol monomethyl ether (mPEG-NH 2, molecular weight is 5000), carry out amidation reaction 8h at room temperature, under stirring condition, obtain the first reaction solution, the first reaction solution is transferred to the ultrafiltration centrifuge tube (molecular weight cut-off is 50kDa), centrifuged at 6000rpm rotating speed earlier 30min, Wash with deionized water, repeat the above proces...

Embodiment 3

[0080] A preparation method of a nano drug complex loaded with paclitaxel, comprising the steps of:

[0081] (1) Preparation of nano drug carrier solution:

[0082] Take graphene oxide and carry out carboxylation treatment to obtain an aqueous solution (concentration of 1 mg / mL) of carboxylated graphene oxide (NGO-COOH), take 20 mL, add hydrochloric acid to adjust the pH to 5.6, and 8 mg of N-hydroxysuccinyl Add imine (NHS) and 10 mg of 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) into NGO-COOH, ultrasonically disperse for 15 min, add 60 mg of amino polydiimide Alcohol monomethyl ether (mPEG-NH 2 , molecular weight is 5000), carry out amidation reaction 24h at room temperature, under stirring condition, obtain the first reaction solution, the first reaction solution is transferred to ultrafiltration centrifuge tube (molecular weight cut-off is 40kDa), centrifuged at 6000rpm rotating speed earlier 30min, Wash with deionized water, repeat the above process ...

technical field

[0001] The invention belongs to the technical field of biomedicine, and in particular relates to a paclitaxel-loaded nano drug complex and a preparation method thereof. Background technique

[0002] Paclitaxel (PTX) is a natural antineoplastic drug, widely used in the treatment of ovarian cancer, breast cancer, lung cancer and other tumors. However, because PTX is poorly soluble in water, has low bioavailability, short half-life and high toxicity, it is necessary to develop a dosage form of paclitaxel clinically to improve its targeting effect on tumors.

[0003] The dosage forms of PTX in clinical application mainly include PTX injection and PTX liposome. However, the dosage form of paclitaxel injection needs to use a mixed solution of co-solvent polyoxyethylene castor oil and ethanol to increase the solubility of PTX. clinical application. And paclitaxel liposome, biocompatibility is good, has avoided the toxic side effect that solubilizing polyoxyethyle...

Examples

Embodiment 1

[0049] A preparation method of a nano drug complex loaded with paclitaxel, comprising the steps of:

[0050] (1) Preparation of nano drug carrier solution:

[0051] Take graphene oxide and carry out carboxylation treatment to obtain an aqueous solution (concentration of 1 mg / mL) of carboxylated graphene oxide (NGO-COOH), take 20 mL, add hydrochloric acid to adjust the pH to 5.6, and 8 mg of N-hydroxysuccinyl Add imine (NHS) and 10 mg of 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) into NGO-COOH, ultrasonically disperse for 5 min, add 100 mg of amino polydiimide Alcohol monomethyl ether (mPEG-NH 2 , molecular weight is 5000), at room temperature, carry out amidation reaction 12h under stirring condition, obtain the first reaction liquid, transfer the first reaction liquid to ultrafiltration centrifuge tube (molecular weight cut-off is 30kDa), centrifuge at 6000rpm at low speed for 30min first , wash with deionized water, repeat the above centrifugation and...

Embodiment 2

[0071] A preparation method of a nano drug complex loaded with paclitaxel, comprising the steps of:

[0072] (1) Preparation of nano drug carrier solution:

[0073] Take graphene oxide and carry out carboxylation treatment to obtain an aqueous solution (concentration of 1 mg / mL) of carboxylated graphene oxide (NGO-COOH), take 20 mL, add hydrochloric acid to adjust the pH to 5.6, and 8 mg of N-hydroxysuccinyl Add imine (NHS) and 10 mg of 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) into NGO-COOH, ultrasonically disperse for 20 min, add 20 mg of amino polydiimide Alcohol monomethyl ether (mPEG-NH 2, molecular weight is 5000), carry out amidation reaction 8h at room temperature, under stirring condition, obtain the first reaction solution, the first reaction solution is transferred to the ultrafiltration centrifuge tube (molecular weight cut-off is 50kDa), centrifuged at 6000rpm rotating speed earlier 30min, Wash with deionized water, repeat the above proces...

Embodiment 3

[0080] A preparation method of a nano drug complex loaded with paclitaxel, comprising the steps of:

[0081] (1) Preparation of nano drug carrier solution:

[0082] Take graphene oxide and carry out carboxylation treatment to obtain an aqueous solution (concentration of 1 mg / mL) of carboxylated graphene oxide (NGO-COOH), take 20 mL, add hydrochloric acid to adjust the pH to 5.6, and 8 mg of N-hydroxysuccinyl Add imine (NHS) and 10 mg of 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) into NGO-COOH, ultrasonically disperse for 15 min, add 60 mg of amino polydiimide Alcohol monomethyl ether (mPEG-NH 2 , molecular weight is 5000), carry out amidation reaction 24h at room temperature, under stirring condition, obtain the first reaction solution, the first reaction solution is transferred to ultrafiltration centrifuge tube (molecular weight cut-off is 40kDa), centrifuged at 6000rpm rotating speed earlier 30min, Wash with deionized water, repeat the above process ...

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