NANOHYBRID DRUG CARRIER PREPARED BY PICKERING EMULSION TEMPLATE METHOD WITH MAGADIITE AS EMULSIFIER AND PREPARATION METHOD THEREFOR

Abstract

A nanohybrid drug carrier prepared by a Pickering emulsion template method with magadiite as an emulsifier and a preparation method therefor. With organic magadiite as the emulsifier and an organic solvent capable of dissolving and dispersing a PLGA as an oil phase, a Pickering drug emulsion is prepared, and then a PLGA-magadiite nanohybrid drug controlled-release carrier is prepared by using a solvent evaporation method.

Claims

1. A method for preparing a nanohybrid drug carrier by a Pickering emulsion template method with magadiite as an emulsifier, wherein comprising the following steps: 1) adding a PLGA, a model drug and an organic magadiite with a contact angle of less than 90 into an oil phase, mechanically stirring and ultrasonically dispersing to even to obtain a mixture A; 2) adding the mixture A into deionized water, stirring and ultrasonically dispersing to obtain a stable O/W Pickering emulsion; and 3) by using a solvent evaporation method, heating up to evaporate an organic solvent of an internal phase, followed by drying to remove water to obtain a nanohybrid drug carrier, which is a PLGA-magadiite nanohybrid drug controlled-release microsphere.

2. A method for preparing a nanohybrid drug carrier by a Pickering emulsion template method with magadiite as an emulsifier, wherein comprising the following steps: 1) adding a PLGA and an organic magadiite with a contact angle of greater than 90 into an oil phase, mechanically stirring and ultrasonically dispersing to even to obtain a mixture B; 2) adding the mixture B into deionized water dissolved with a model drug, stirring and ultrasonically dispersing to obtain a stable W/O Pickering emulsion; and 3) by using a solvent evaporation method, evaporating an organic solvent of an external phase, followed by heating up and drying to remove water in an internal phase to obtain a nanohybrid drug controlled-release carrier which is a PLGA-magadiite nanohybrid drug controlled-release membrane.

3. The method according to claim 1, wherein the model drug is a water-insoluble drug, and a volume ratio of oil to water in the step 2) is less than 1.

4. The method according to claim 2, wherein the model drug is a water-soluble drug, and a volume ratio of oil to water in the step 2) is greater than 1.

5. The method according to claim 1, wherein the model drug is levonorgestrel or paclitaxel.

6. The method according to claim 2, wherein the model drug is doxorubicin.

7. The method according to claim 1, wherein the oil phase is methylene chloride or ethyl acetate.

8. The method according to claim 1, characterized in that, wherein the organic magadiite is obtained by modifying a magadiite with one of an organic quaternary phosphonium salt, an organic quaternary ammonium salt and a silane.

9. A nanohybrid drug carrier prepared by the method according to claim 1.

10. The nanohybrid drug carrier according to claim 9, wherein the nanohybrid drug carrier comprises the following components: an organic magadiite, a PLGA and a drug.

11. The method according to claim 2, wherein the oil phase is methylene chloride or ethyl acetate.

12. The method according to claim 2, wherein the organic magadiite is obtained by modifying a magadiite with one of an organic quaternary phosphonium salt, an organic quaternary ammonium salt and a silane.

13. A nanohybrid drug carrier prepared by the method according to claim 2.

14. The nanohybrid drug carrier according to claim 13, wherein the nanohybrid drug carrier comprises the following components: an organic magadiite, a PLGA and a drug.

15. A nanohybrid drug carrier prepared by the method according to claim 3.

16. The nanohybrid drug carrier according to claim 15, wherein the nanohybrid drug carrier comprises the following components: an organic magadiite, a PLGA and a drug.

17. A nanohybrid drug carrier prepared by the method according to claim 4.

18. The nanohybrid drug carrier according to claim 17, wherein the nanohybrid drug carrier comprises the following components: an organic magadiite, a PLGA and a drug.

19. A nanohybrid drug carrier prepared by the method according to claim 8.

20. The nanohybrid drug carrier according to claim 19, wherein the nanohybrid drug carrier comprises the following components: an organic magadiite, a PLGA and a drug.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0033] FIG. 1 is a microscopic schematic diagram of a process of preparing a PLGA-magadiite nanohybrid drug controlled-release microsphere;

[0034] FIG. 2 is a microscopic schematic diagram of a process of preparing a PLGA-magadiite nanohybrid drug controlled-release membrane;

[0035] FIG. 3a is a SEM graph of pure magadiite;

[0036] FIG. 3b is a SEM graph of magadiite modified by cetyltriphenyl quaternary phosphonium salt;

[0037] FIG. 4 is a polarization microscope graph of an emulsion; and

[0038] FIG. 5 is a TEM graph of a PLGA-magadiite encapsulating drug 5-fluorouracil.

DETAILED DESCRIPTION OF THE EMBODIMENTS

[0039] The concrete implementation of the invention is further described hereinafter with reference to the accompanying drawings and embodiments, but the invention is not limited thereto.

Embodiment 1

[0040] 5 g of magadiite (see FIG. 3a for SEM graph) and 1 g of cetyltriphenyl phosphonium bromide were weighed and put into a 500 ml beaker, and then added with 100 ml of deionized water to form a mixture. The beaker was placed in a magnetic stirring water bath kettle and the mixture was stirred for 24 hours at 80 C. After the reaction was completed, a product was filtered and washed for three times with deionized water. A resulting filtrate was dried for 6 hours at 80 C., and then grinded to obtain organic magadiite (see FIG. 3b for SEM graph). 2 mg of levonorgestrel, 1 g of organic magadiite and 1 g of PLGA were weighed, mixed and dissolved in 50 ml of ethyl acetate to form a mixture which was then placed in a 100 ml beaker after mixing. After the beaker was placed in a magnetic stirring water bath kettle and the mixture was stirred for 6 hours at room temperature, the beaker was placed in an ultrasound environment (40 KHz) for 3 hours, and then the mixture was added into deionized water, wherein a volume ratio of water to oil was 1:2. A stable and even milky Pickering emulsion (see FIG. 4 for polarization microscope graph) was obtained by ultrasonic mixing, and then the oil phase ethyl acetate was removed by using a solvent evaporation method, and finally the emulsion was dried at 80 C. in vacuum to obtain a nanohybrid drug controlled-release microsphere encapsulating drug levonorgestrel. The structural diagram of the nanohybrid drug controlled-release microsphere is shown in FIG. 1. The modified organic magadiite acts as a hard phase to support and is wound with the PLGA to form the microsphere in which the drug was contained.

Embodiment 2

[0041] 5 g of magadiite and 1 g of cetyltrimethyl ammonium bromide were weighed and put into a 500 ml beaker, and then added with 100 ml of deionized water to form a mixture. The beaker was placed in a magnetic stirring water bath kettle and the mixture was stirred for 24 hours at 80 C. After the reaction was completed, a product was filtered and washed for three times with deionized water. A resulting filtrate was dried for 6 hours at 80 C., and then grinded to obtain organic magadiite. 1 g of organic magadiite and 1 g of PLGA were weighed, mixedly and dissolved in 50 ml of methylene chloride to form a mixture which was placed in a 100 ml beaker after ultrasonic mixing. 2 mg of doxorubicin was dissolved in 50 ml of deionized water, an oil phase was mixed with an aqueous phase, a volume ratio of water to oil was 2:1, and then the mixture was placed in an ultrasound environment (40 KHz) for 3 hours to obtain a stable and milky Pickering emulsion. After that, the oil phase methylene chloride was removed by using a solvent evaporation method, and finally the emulsion was dried at 80 C. in vacuum to obtain a nanohybrid drug controlled-release membrane containing drug doxorubicin. The structural diagram of the nanohybrid drug controlled-release membrane is shown in FIG. 2.

Embodiment 3

[0042] 5 g of magadiite and 1 g of cetyltrimethyl quaternary phosphonium salt were weighed and put into a 500 ml beaker, and then added with 100 ml of deionized water to form a mixture. The beaker was placed in a magnetic stirring water bath kettle and the mixture was stirred for 24 hours at 80 C. After the reaction was completed, a product was filtered and washed for three times with deionized water. A resulting filtrate was dried for 6 hours at 80 C., and then grinded to obtain organic magadiite. 2 mg of 5-fluorouracil, 1 g of organic magadiite and 1 g of PLGA were weighed, mixed and dissolved in 50 ml of ethyl acetate to form a mixture which was then placed in a 100 ml beaker after even ultrasonic mixing. After the beaker was placed in a magnetic stirring water bath kettle and the mixture was stirred for 6 hours at room temperature, the beaker was placed in an ultrasound environment (40 KHz) for 3 hours, and then the mixture was added into deionized water, wherein a volume ratio of water to oil was 8:9. A stable and even milky Pickering emulsion was obtained by ultrasonic mixing, then the oil phase ethyl acetate was removed by using a solvent evaporation method, and finally the emulsion was dried at 80 C. in vacuum to obtain a nanohybrid drug controlled-release microsphere encapsulating drug 5-fluorouracil. FIG. 5 is a TEM graph of PLGA-magadiite encapsulating drug 5-fluorouracil.

[0043] The above-mentioned embodiments of the invention are merely examples for clearly illustrating the invention and are not intended to limit the embodiments of the invention. For those of ordinary skills in the art, other different forms of changes or variations can be made on the basis of the above description. It is not necessary or possible to exhaust all the embodiments here. Any change, equivalent substitution, and improvement made within the spirit and principle of the invention shall fall within the protection scope of the claims of the invention.