CN107335064A - A kind of nano-particle for macrophage targeted delivery of drugs and preparation method thereof - Google Patents
A kind of nano-particle for macrophage targeted delivery of drugs and preparation method thereof Download PDFInfo
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- CN107335064A CN107335064A CN201710563295.7A CN201710563295A CN107335064A CN 107335064 A CN107335064 A CN 107335064A CN 201710563295 A CN201710563295 A CN 201710563295A CN 107335064 A CN107335064 A CN 107335064A
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Abstract
The invention discloses a kind of nano-particle for macrophage targeting and preparation method thereof.Prepared first by oil-in-water solvent evaporation method and carry curcumin nano particle, targeting modification then is carried out with chondroitin sulfate to this nanoparticle surface.The particle diameter of the nano-particle is 281.5 ± 3.51 nm, narrower particle diameter distribution and higher drugloading rate.Chondroitin sulfate is introduced nanoparticle surface by the present invention, is observed by SEM, nano-particle is rounded or oval, and size is more uniform.Compared with the nano-particle that surface is modified with carboxymethyl cellulose, the nano-particle of chondroitin sulfate modification significantly improves cell phagocytosis efficiency and antiphlogistic effects so as to effectively enhance the therapeutic efficiency of colitis.
Description
Technical field
The invention belongs to nano-medicament carrier technical field, and in particular to one kind load medicine porous nano particle preparation method,
Characterize and apply.
Background technology
Ulcerative colitis（Ulcerative colitis, UC）It is most important one kind in IBD, main
Clinical symptoms is suffer from diarrhoea, had blood in stool, Body weight loss, stomachache, fatigue and fever etc..According to data, ulcerative colitis is in Europe
Man of the U.S. incidence of disease is higher, and by taking the U.S. as an example, the incidence of disease is up to 2 ‰.UC is generally elapsed over time, and symptom runs down.Pass
The medicine of system mainly includes minosalicylates, drugs（Such as 5-aminosalicylic acid）, immunodepressant class medicine（Such as ammonia first
Purine）And glucocorticoid medicine（Such as budesonide）Deng.
In recent years, with Poly(D,L-lactide-co-glycolide（Polylactic-co-glycolic acid, PLGA）For base
Micro-, the nano-particle of plinth have obtained extensive research, its have good biocompatibility, nonirritant, non-immunogenicity and
The advantages that medicine controlled releasing.Curcumin（Curcumin, CUR）It is to be extracted from the rhizome of the plants such as Zingiber turmeric turmeric, root tuber of aromatic turmeric
A kind of active material, it is comparatively safe for the mankind, but is easily decomposed in neutral and alkaline environment, and stability is poor, these
Defect causes its not yet large-scale application in clinic.
Therefore, a practicable therapeutic scheme is provided in order to be treated to UC, we are prepared into PLGA parcels CUR and received
Rice corpuscles, while in particle surface modified chondroitin sulfate, compared to more traditional no targeted nano-particle, chondroitin sulfate modification
Nano-particle drug cell phagocytosis faster, antiphlogistic effects are more preferable, turn into a kind of potential UC therapeutic strategies.
The content of the invention
In view of this, an object of the present invention is to provide a kind of nano-particle available for macrophage targeting, its
With good biocompatibility, stability, available for the treatment of ulcerative colitis, the second object of the present invention is to provide
The preparation method of above-mentioned targeted nano-particle.
For achieving the above object, technical scheme is：
The preparation method for carrying medicine targeted nano-particle comprises the following steps：
（1）Weigh Poly(D,L-lactide-co-glycolide（Polylactic-co-glycolic acid, PLGA）And curcumin
（CUR）, it is dissolved in dichloromethane and methanol（Methylene chloride/methanol=4:1）, wiring solution-forming；
（2）By step（1）Obtain solution to be added dropwise in polyvinyl alcohol water solution, be made into emulsion；
（3）By step（2）Middle gained emulsion is immediately placed in ice bath, carries out ultrasound；
（4）Emulsion after ultrasound is poured into polyvinyl alcohol water solution rapidly；
（5）At ambient temperature, the organic solvent in emulsion step (4) obtained fully volatilizees；
（6）Centrifuged again, collect nano-particle, and be washed with deionized 3 times；
（7）By step（6）Obtained nano-particle is suspended in the sodium-acetate buffer of pH=6, adds the sulphur containing EDC and NHS
Aching and limp ossein solution, the nano-particle of surface modification chondroitin sulfate can be obtained；
（8）The nano-particle of surface modification chondroitin sulfate is collected by centrifugation again, and is washed with deionized 3 times；
（9）By step（8）Obtained nano-particle is dispersed in the aqueous solution of trehalose again；
（10）Above-mentioned nano-particle is freezed again, it is standby to be stored in -20 degrees Celsius of refrigerators.
Preferably, the step（1）In solution in PLGA mass concentration be 25-100 mg/mL, CUR quality it is dense
Spend for 2-8 mg/mL.
Preferably, the step（2）The mass concentration of polyvinyl alcohol is 1-5% in middle polyvinyl alcohol water solution, polyvinyl alcohol
The volume of the aqueous solution is step（1）2 times of obtained solution.
Preferably, the step（3）In, ultrasonic parameter is ultrasonic amplitude 20 ~ 50%, every time 5 ~ 20 s, is spaced 1 ~ 5 s,
Ultrasonic total duration is 0.5 ~ 3 min.
Preferably, the step（4）In, the mass concentration of polyvinyl alcohol is 0 ~ 0.5% in polyvinyl alcohol water solution, volume
For step（3）3-40 times of obtained emulsion volume.
Preferably, the step（6）And step（8）In, the parameter for centrifuging selection is that centrifugation rate is 12000 rpm, from
The heart time is 8-20 min.
Preferably, the step（9）In, trehalose concentration is 5-10% in aqueous trehalose, and nano-particle is dissolved in trehalose
PLGA mass concentration is 25-100 mg/mL after the aqueous solution.
Preferably, the step（10）In, freeze-drying is carried out in accordance with the following methods：After -80 degrees Celsius of freeze overnights
It is placed in freeze dryer and freezes 12~36 h.
Relative to existing technology, the advantage of the invention is that：
1. the present invention, using PLGA as drug carrier material, preparation method is oil-in-water solvent evaporation method, whole preparation process is simple
It is single quick, short preparation period, yield height.
2. the present invention wraps up CUR by PLGA and prepares medicine-carried nano particles, it is bad, unstable, easy to improve CUR water solubilitys
Decompose etc., CUR is preferably delivered to patient part and played a role, increases curative effect.
3. significantly carried as targeted molecular, the nano-particle of chondroitin sulfate modification invention introduces chondroitin sulfate
High cell phagocytosis efficiency and antiphlogistic effects, so as to effectively enhance the therapeutic efficiency of colitis.
Brief description of the drawings
In order that the object, technical solutions and advantages of the present invention are clearer, the present invention is made below in conjunction with accompanying drawing into
The detailed description of one step, wherein：
Fig. 1：The field emission scanning electron microscope of the nano-particle of carboxymethyl cellulose modification and the nano-particle of chondroitin sulfate modification
Figure.
Fig. 2：The external phagocytosis of the nano-particle of carboxymethyl cellulose modification and the nano-particle of chondroitin sulfate modification is real
Test.
Fig. 3：The extracorporeal anti-inflammatory of the nano-particle of carboxymethyl cellulose modification and the nano-particle of chondroitin sulfate modification is real
Test.
Embodiment
Hereinafter with reference to accompanying drawing, the preferred embodiments of the present invention are described in detail.
Embodiment 1
Embodiment 1 is the preparation method of the load CUR nano-particles of chondroitin sulfate modification, is comprised the following steps：
（1）The mg of the PLGA 100 and mg of CUR 6 are weighed to be dissolved in jointly in 2 mL dichloromethane and methanol solution；
（2）Above-mentioned organic solution is added dropwise in the poly-vinyl alcohol solutions of 4 mL 5%；
（3）Above-mentioned solution is immediately placed in ice bath, carries out ultrasound, amplitude 50%, 10 s, is spaced 1s every time, and ultrasonic total duration is 1
min；
（4）After ultrasound, above-mentioned emulsion is poured into rapidly in 60 mL 0.05% poly-vinyl alcohol solution；
（5）At ambient temperature, organic solvent in above-mentioned emulsion is volatilized；
（7）Above-mentioned nano-particle is collected by centrifugation, and is washed with deionized 3 times, centrifugation rate is 12000 rpm, centrifugation time
For 20 min；
（8）Made particle and chondroitin sulfate solution are reacted at room temperature 2 hours；
（9）Above-mentioned nano-particle is collected by centrifugation, and is washed with deionized 3 times, centrifugation rate is 12000 rpm, centrifugation time
For 20 min；
（10）Above-mentioned nano-particle is dispersed in the aqueous solution of 1 mL containing 10% trehalose again；
（11）Above-mentioned nano-particle is freezed, is stored in -20 DEG C of refrigerators；
Embodiment 2
Embodiment 2 is the preparation method of the load CUR nano-particles of carboxymethyl cellulose modification, is comprised the following steps：
（1）The mg of the PLGA 100 and mg of CUR 6 are weighed to be dissolved in jointly in 2 mL dichloromethane and methanol solution；
（2）Above-mentioned organic solution is added dropwise in the poly-vinyl alcohol solutions of 4 mL 5%；
（3）Above-mentioned solution is immediately placed in ice bath, carries out ultrasound, amplitude 50%, 10 s, is spaced 1s every time, and ultrasonic total duration is 1
min；
（4）After ultrasound, above-mentioned emulsion is poured into rapidly in 60 mL 0.05% poly-vinyl alcohol solution；
（5）At ambient temperature, organic solvent in above-mentioned emulsion is volatilized；
（7）Above-mentioned nano-particle is collected by centrifugation, and is washed with deionized 3 times, centrifugation rate is 12000 rpm, centrifugation time
For 20 min；
（8）Made particle and cmc soln are reacted at room temperature 2 hours；
（9）Above-mentioned nano-particle is collected by centrifugation, and is washed with deionized 3 times, centrifugation rate is 12000 rpm, centrifugation time
For 20 min；
（10）Above-mentioned nano-particle is dispersed in the aqueous solution of 1 mL containing 10% trehalose again；
（11）Above-mentioned nano-particle is freezed, is stored in -20 DEG C of refrigerators；
Experiment 1：The pattern of nano-particle is observed by field emission scanning electron microscope.Before analysis, nano-particle passes through
Vacuum spray platinum processing.
Fig. 1 is the field emission scanning electron microscope figure of nano-particle.（a）Figure is the load CUR nanoparticles of carboxymethyl cellulose modification
Son；（b）Figure is the load CUR nano-particles of chondroitin sulfate modification.Obtained nanoparticle is can be seen that from obtained electromicroscopic photograph
Son is in spherical, and surface is smooth, and pore size is more uniform.
Experiment 2：Cell phagocytosis experiment, cell used is Raw264.7, can significantly be found out from Fig. 2 soft with sulfuric acid
The nano particle cell phagocytosis of ossein modification is more efficient, during 0.5 h, the nano particle cell phagocytosis of chondroitin sulfate modification
63.99%, and the nano particle cell phagocytosis only 21.28% of carboxymethyl cellulose modification.The modification of this explanation chondroitin sulfate
Drastically increase cell phagocytosis efficiency.
Experiment 3：In numerous inflammatory cytokines, what is played a major role is TNF-α, IL-1 β, IL-6, IL-8 etc..We
TNF-α therein, IL-6 and IL-12 are detected, it will be seen that the nanometer of chondroitin sulfate modification from Fig. 3
Particle inhibits the expression of inflammatory factor really, and compared with the nano-particle of carboxymethyl cellulose modification, it has more preferable
Antiphlogistic effects.
Finally illustrate, above example is only used for illustrating technical scheme and unrestricted, although passing through ginseng
According to the preferred embodiments of the present invention, invention has been described, it should be appreciated by those of ordinary skill in the art that can
So that various changes are made to it in the form and details, the present invention that is limited without departing from appended claims
Spirit and scope.
Claims (8)
- A kind of 1. nano-particle for macrophage targeted delivery of drugs and preparation method thereof, it is characterised in that：Utilize solvent Volatility process prepares nano-particle, comprises the following steps：（1）Weigh Poly(D,L-lactide-co-glycolide（Polylactic-co-glycolic acid, PLGA）And curcumin （CUR）, it is dissolved in dichloromethane and methanol（Methylene chloride/methanol=4:1）, wiring solution-forming；（2）By step（1）Obtain solution to be added dropwise in polyvinyl alcohol water solution, be made into emulsion；（3）By step（2）Middle gained emulsion is immediately placed in ice bath, carries out ultrasound；（4）Emulsion after ultrasound is poured into polyvinyl alcohol water solution rapidly；（5）At ambient temperature, the organic solvent in emulsion step (4) obtained fully volatilizees；（6）Centrifuged again, collect nano-particle, and be washed with deionized 3 times；（7）By step（6）Obtained nano-particle is suspended in the sodium-acetate buffer of pH=6, adds the sulphur containing EDC and NHS Aching and limp ossein solution, the nano-particle of surface modification chondroitin sulfate can be obtained；（8）The nano-particle of surface modification chondroitin sulfate is collected by centrifugation again, and is washed with deionized 3 times；（9）By step（8）Obtained nano-particle is dispersed in the aqueous solution of trehalose again；（10）Above-mentioned nano-particle is freezed again, it is standby to be stored in -20 degrees Celsius of refrigerators.
- 2. a kind of nano-particle for macrophage targeted delivery of drugs according to claim 1 and preparation method thereof, It is characterized in that：The step（1）In solution in PLGA mass concentration be 25-100 mg/mL, CUR mass concentration be 2-8 mg/mL。
- 3. a kind of nano-particle for macrophage targeted delivery of drugs according to claim 1 and preparation method thereof, It is characterized in that：The step（2）The mass concentration of polyvinyl alcohol is 1-5% in middle polyvinyl alcohol water solution, and polyvinyl alcohol is water-soluble The volume of liquid is step（1）2 times of obtained solution.
- 4. a kind of nano-particle for macrophage targeted delivery of drugs according to claim 1 and preparation method thereof, It is characterized in that：The step（3）In, ultrasonic parameter is ultrasonic amplitude 20 ~ 50%, every time 5 ~ 20 s, is spaced 1 ~ 5 s, ultrasound Total duration is 0.5 ~ 3 min.
- 5. a kind of nano-particle for macrophage targeted delivery of drugs according to claim 1 and preparation method thereof, It is characterized in that：The step（4）In, the mass concentration of polyvinyl alcohol is 0 ~ 0.5% in polyvinyl alcohol water solution, and volume is step Suddenly（3）3-40 times of obtained emulsion volume.
- 6. a kind of nano-particle for macrophage targeted delivery of drugs according to claim 1 and preparation method thereof, It is characterized in that：The step（6）And step（8）In, the parameter that centrifuges selection is that centrifugation rate is 12000 rpm, during centrifugation Between be 8-20 min.
- 7. a kind of nano-particle for macrophage targeted delivery of drugs according to claim 1 and preparation method thereof, It is characterized in that：The step（9）In, trehalose concentration is 5-10% in aqueous trehalose, and it is water-soluble that nano-particle is dissolved in trehalose PLGA mass concentration is 25-100 mg/mL after liquid.
- 8. a kind of nano-particle for macrophage targeted delivery of drugs according to claim 1 and preparation method thereof, It is characterized in that：The step（10）In, freeze-drying is carried out in accordance with the following methods：It is placed in after -80 degrees Celsius of freeze overnights 12~36 h are freezed in freeze dryer.
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Cited By (3)
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| CN113244409A (en) * | 2021-05-27 | 2021-08-13 | 浙江大学 | Nano particles with synergistic enhancement effects of active oxygen scavenging and anti-inflammatory effects |
| CN117959263A (en) * | 2024-04-01 | 2024-05-03 | 吉林大学 | Preparation and application of drug-loaded frozen macrophage for promoting cytoburied effect |
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| CN102335135A (en) * | 2010-07-19 | 2012-02-01 | 谢清河 | Functionalized nanoparticle, method for preparing the same and application thereof |
| CN106177986A (en) * | 2016-08-16 | 2016-12-07 | 国家纳米科学中心 | A kind of lipopolymer medicine-carried nano particles and its preparation method and application |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108743540A (en) * | 2018-06-20 | 2018-11-06 | 西南大学 | A kind of preparation method and applications of the multifunctional nano drug based on fibroin |
| CN113244409A (en) * | 2021-05-27 | 2021-08-13 | 浙江大学 | Nano particles with synergistic enhancement effects of active oxygen scavenging and anti-inflammatory effects |
| CN117959263A (en) * | 2024-04-01 | 2024-05-03 | 吉林大学 | Preparation and application of drug-loaded frozen macrophage for promoting cytoburied effect |
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