CN107158382A - Based on hollow Prussian blue thermostimulation response type insoluble drug release nano-carrier and preparation method thereof - Google Patents
Based on hollow Prussian blue thermostimulation response type insoluble drug release nano-carrier and preparation method thereof Download PDFInfo
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Abstract
The invention discloses based on hollow Prussian blue thermostimulation response type insoluble drug release nano-carrier and preparation method thereof, it is characterised in that：Nano-carrier be using hollow prussian blue nano particle as shell mechanism, shell mechanism it is hollow in be filled with Thermo-sensitive material；The medicaments uniformity of required load is mixed in Thermo-sensitive material, so as to constitute medicament-carried nano carrier.The present invention is based on medicament nano carrier technique, Prussian blue and Thermo-sensitive material is combined and is used as thermal response stimulating unit, phase in version physical phenomenon and Prussian blue high photo-thermal conversion efficiency based on Thermo-sensitive material, so that ambient temperature is increased to over Thermo-sensitive material boiling point by nano-carrier quickly under the irradiation of 808nm laser, trigger medicine quick release.
Description
Technical field
The invention belongs to technical field of nano material, and in particular to a kind of thermostimulation response type insoluble drug release nano-carrier and
Its preparation method.
Background technology
In treatment of cancer, chemotherapy is one of important means of clinical anticancer, and chemotherapeutics due to itself
Cytotoxicity, while cancer cell is killed, the side effect for bringing patient is also huge, and often systemic poison is secondary
Effect.Stimuli responsive release is that one kind can reduce toxic side effect, and the solution of utilization ratio of drug can be improved again.With medicine
The continuous propulsion of nano-carrier research, stimuli responsive type insoluble drug release nano-carrier is increasingly becoming the emphasis of researchers' concern.
Stimuli responsive type insoluble drug release nano-carrier is that have using the materials synthesis of one or more bio-compatibles specific outer
The nanometer of such as protonation, hydrolysis, supermolecule conformation change or physical phase transition responding ability is carried out under source property or endogenous stimulus
Carrier, the purpose in diseased region fixed point release can be reached by loading medicine by it.External source sexual stimulus includes heat, light, magnetic field
Deng endogenous stimulus concentration, pH value, redox gradient including enzyme etc..
Prussian blue is a kind of fabulous material of biocompatibility, FDA (Food and Drug Adminstration) (Food and Drug
Administration) certification its be harmless material, and it is medical in thallium poisoning antidote to ratify in 2003 its.In recent years
The research come is found, Prussian blue while also with very strong near-infrared absorption ability and higher photo-thermal conversion efficiency, being
One outstanding photo-thermal therapy agent.The research that prussian blue nano particle is used for stimuli responsive type nano-carrier is lacked at present, its
In it is representative be to be combined prussian blue nano particle with the gelatin that medicine is crosslinked, utilize endogenous stimulus --- gelatin
Hydrolase is as stimulus, and the gelatin hydrolysis that will be combined with particle reaches the purpose of stimuli responsive type insoluble drug release.But it is because bright
Glue hydrolase is equally existed in normal tissue cell, and there is also certain restricted in the selection of medicine.
The content of the invention
The purpose of the present invention is to be to provide a kind of based on hollow Prussian blue thermostimulation response type insoluble drug release nanometer
Carrier, it is expected that exogenous stimuli responsive type ability can be made it have, it is to avoid the injury to normal cell, and is applied to simultaneously
Hydrophilic and dewatering medicament.
The present invention adopts the following technical scheme that to solve technical problem：
The present invention is based on hollow Prussian blue thermostimulation response type insoluble drug release nano-carrier, and its feature is：It is described
Nano-carrier be using hollow prussian blue nano particle as shell mechanism, the shell mechanism it is hollow in be filled with Thermo-sensitive
Material；The medicaments uniformity of required load is mixed in the Thermo-sensitive material, so as to constitute medicament-carried nano carrier；
Using the solid-liquid phase change phenomenon of the Thermo-sensitive material, the mode for realizing medicine response release is：Less than described
Under the temperature environment of Thermo-sensitive material melting point, the Thermo-sensitive material of medicine is mixed with the hollow prussian blue nano particle
In solid-state, medicine does not discharge；When with outside stimulation in nano-carrier, the hollow prussian blue nano particle produces heat
Amount, when the temperature of boring position is reached the Thermo-sensitive material melting point and the above, is mixed with the Thermo-sensitive material of medicine
Be in a liquid state in the hollow prussian blue nano particle, and from hollow prussian blue nano particle it is mesoporous from overflow, realize
Insoluble drug release.
It is preferred that, the Thermo-sensitive material is tetradecyl alchohol, paraffin, pentadecanol or tetradecylic acid.
The outside stimulus is the thermostimulation that light stimulus, microwave stimulation, magnetic stimulation, ultrasound stimulation or body heat trigger.Its
The thermostimulation that middle body heat triggers refers to when human body temperature rises above the fusing point of Thermo-sensitive material, hollow prussian blue nano
The temperature of particle is raised simultaneously so that the temperature of boring position reach the Thermo-sensitive material melting point and more than.
The nano-carrier of the present invention is simultaneously suitable for hydrophily or hydrophobic drug, such as adriamycin, camptothecine, catharanthus roseus
Alkali, taxol, gemcitabine or capecitabine etc..
The above-mentioned preparation method based on hollow Prussian blue thermostimulation response type insoluble drug release nano-carrier, including it is as follows
Step：
(1) hollow prussian blue nano particle is prepared by hydro-thermal method first；
(2) temperature-sensitive material and medicine are dissolved in volatile organic solvent, obtain mixed solution；Will be described hollow general
Shandong scholar indigo plant nano-particle is distributed in identical organic solvent, obtains nano-particle re-suspension liquid；
(3) after mixing the mixed solution and the nano-particle re-suspension liquid, stirring makes part dissolved with temperature-sensitive material
With the organic solvent of medicine enter hollow prussian blue nano particle it is hollow in；Then heat to the boiling point of the organic solvent
More than, constant temperature stirring, makes hollow prussian blue nano inside particles and outside organic solvent volatilization is complete, and acquisition is scattered in liquid
Medicament-carried nano support dispersion in state temperature-sensitive material；
(4) constant temperature is continued, and heating degree is not less than Thermo-sensitive material melting point in the medicament-carried nano support dispersion
Deionized water, stirring is then centrifuged for separation, obtains medicament-carried nano carrier；At room temperature, the thermal sensitivity in the medicament-carried nano carrier
Material solidification.
By taking tetradecyl alchohol as an example, above-mentioned preparation method comprises the following steps：
(1) hollow prussian blue nano particle is prepared by hydro-thermal method first；
(2) 100~600mg tetradecyl alchohols are dissolved in 6mL, the methanol solution of 1~2mg/mL medicines, stirred at 20~50 DEG C
Mix to well mixed, obtain mixed solution；Hollow prussian blue nano particle described in 5~30mg is distributed to 3mL methanol solutions
In, obtain nano-particle re-suspension liquid；
(3) after mixing the mixed solution and the nano-particle re-suspension liquid, 1~2h is stirred, makes part dissolved with 14
The methanol solution of alcohol and medicine enter hollow prussian blue nano particle it is hollow in；70~90 DEG C are then heated to, constant temperature is stirred
2~4h is mixed, makes hollow prussian blue nano inside particles and outside methanol solution volatilization is complete, acquisition is scattered in liquid 14
Medicament-carried nano support dispersion in alcohol；
(4) continue constant temperature, and in the medicament-carried nano support dispersion 70~90 DEG C of heating degree deionized water, stir
30min；Then it is set as centrifuging on 40 DEG C of centrifuge in temperature, centrifugal rotational speed 13000r/min, centrifugation time
10min, obtains medicament-carried nano carrier；At room temperature, the tetradecyl alchohol solidification in the medicament-carried nano carrier.
In centrifugal process, the medicament-carried nano carrier in tetradecyl alchohol is transferred to aqueous phase and precipitated, and tetradecyl alchohol density ratio water is small, floats
With superjacent.
As shown in figure 1, by taking Thermo-sensitive material tetradecyl alchohol as an example, it is colorless solid at normal temperatures, and its fusing point is 38 DEG C, high
In normal body temperature in human body, with the potentiality as stimuli responsive type insoluble drug release nano-carrier composition material.By itself and medicine
It is loaded into simultaneously in hollow prussian blue nano particle, during less than 38 DEG C, tetradecyl alchohol hybrid medicine is mutually changed into solid, using near red
Outer light irradiation etc. stimulates Prussian blue generation heat, environment temperature is higher than 38 DEG C, tetradecyl alchohol is mutually changed into liquid and discharges medicine
Thing.This stimuli responsive type drug delivery system is all effective for hydrophilic drugs or dewatering medicament.
Beneficial effects of the present invention are embodied in：
1st, nano-carrier of the invention has thermostimulation response medicine releasability, while still outstanding photo-thermal therapy
Agent, is a kind of form of photo-thermal therapy and chemotherapy combined.
2nd, nano-carrier of the invention is that can load hydrophilic drugs can load dewatering medicament again, overcomes general nanometer
Carrier single can only load hydrophilic or dewatering medicament deficiency.
3rd, preparation process of the present invention is simple, mild condition, the possibility with large-scale production, with industry and practical application
Potentiality.
4th, material used in the present invention has good biocompatibility, to human body without direct or indirect toxic action,
Human body can be discharged, no genotoxic potential.
5th, nano-carrier of the invention has good dispersiveness and stability, is conducive to Clinical practice.
6th, thermostimulation response type nano carrier of the invention, its external source sexual stimulus used can be 808nm near infrared lights, make
Response raise and carries out insoluble drug release for temperature, such mode reduces medicine to other histiocytic injuries, realization
The Targeting delivery of medicine, improves the utilization rate of medicine.
Brief description of the drawings
Fig. 1 is principle schematic of the invention；
Fig. 2 is the hollow prussian blue nano particle (Fig. 2 a) for preparing and the blank nano-carrier for not carrying medicine in embodiment 1
Uv absorption spectra (Fig. 2 b)；
Fig. 3 is that the nano-carrier of carrying hydrophilic drugs adriamycin prepared by embodiment 2 is carried with the blank nanometer in embodiment 1
Carrying dewatering medicament camptothecine prepared by the ultra-violet absorption spectrum comparison diagram (Fig. 3 a) and embodiment 3 of body and free adriamycin
Nano-carrier and embodiment 1 in blank nano-carrier and free camptothecine ultra-violet absorption spectrum comparison diagram (Fig. 3 b).
Fig. 4 is the thermogravimetric analysis figure of medicament-carried nano carrier prepared by hollow prussian blue nano particle and embodiment 2.
Fig. 5 a are the heating curve figure of the medicament-carried nano carrier aqueous dispersions of various concentrations in embodiment 2, and Fig. 5 b are concentration
The corresponding heating stability curve figure of 150 μ g/mL medicament-carried nano carrier aqueous dispersions.
Fig. 6 a are the insoluble drug release of the obtained nano-carrier for carrying hydrophilic drugs adriamycin of embodiment 2 at different temperatures
Curve, Fig. 6 b are that the insoluble drug release of the obtained nano-carrier for carrying dewatering medicament camptothecine of embodiment 3 at different temperatures is bent
Line,
Fig. 7 a are medicine of the obtained nano-carrier for carrying hydrophilic drugs adriamycin of embodiment 2 under interruption laser irradiation
Release profiles, Fig. 7 b are medicine of the obtained nano-carrier for carrying dewatering medicament camptothecine of embodiment 3 under interruption laser irradiation
Thing release profiles.
Fig. 8 a are the load of blank nano-carrier and embodiment 2 in adriamycin, the embodiment 1 of dissociating when being irradiated without laser
Medicine nano-carrier is to the fragmentation effect of HeLa cells, and Fig. 8 b are to HeLa cells by three during 808nm laser irradiation 5min
Fragmentation effect.
Fig. 9 a are the load of blank nano-carrier and embodiment 3 in camptothecine, the embodiment 1 of dissociating when being irradiated without laser
Medicine nano-carrier is to the fragmentation effect of HeLa cells, and Fig. 9 b are to HeLa cells by three during 808nm laser irradiation 5min
Fragmentation effect.
Embodiment
Embodiment 1
The present embodiment is prepared as follows blank nano-carrier：
(1) hollow prussian blue nano particle is prepared by hydro-thermal method first：
Weigh 3g polyvinylpyrrolidone (PVP) be dissolved in 40mL 0.01mol/L hydrochloric acid solution, stirring to completely it is molten
Solution, adds the 132mg potassium ferricyanide, stirs to being completely dissolved, and is placed at 80 DEG C and reacts 20 hours, obtains mesoporous Prussia
It is blue；
By the 20mg mesoporous Prussian blue 0.1mol/L for being dissolved in 20mL hydrochloric acid solution, 200mg polyethylene is added
Pyrrolidones, is stirred 1 hour, is placed at 140 DEG C and is reacted 2 hours, obtains hollow prussian blue nano particle；
(2) 300mg tetradecyl alchohols are dissolved in 6mL methanol solutions, are stirred at 50 DEG C to well mixed, obtain tetradecyl alchohol molten
Liquid；The hollow prussian blue nano particles of 15mg are distributed in 3mL methanol solutions, nano-particle re-suspension liquid is obtained；
(3) after mixing tetradecyl alchohol solution and nano-particle re-suspension liquid, 1h is stirred, makes part molten dissolved with the methanol of tetradecyl alchohol
Liquid enter hollow prussian blue nano particle it is hollow in；Then heat to 70 DEG C, constant temperature stirring 4h makes hollow Prussian blue receive
The inside and outside methanol solution volatilization of rice corpuscles is complete, obtains the blank nano-carrier being scattered in liquid tetradecyl alchohol and disperses
Liquid；
(4) continue constant temperature, and add the deionized water of temperature 70 C in blank nano-carrier dispersion liquid, stir 30min；So
It is set as centrifuging on 40 DEG C of centrifuge in temperature afterwards, centrifugal rotational speed 13000r/min, centrifugation time 10min obtain empty
White nano-carrier；At room temperature, the tetradecyl alchohol solidification in blank nano-carrier.
Fig. 2 a are the ultra-violet absorption spectrum of hollow prussian blue nano particle, and its characterizing method is：By the hollow general Shandong of gained
Scholar indigo plant nano-particle the aqueous solution be diluted to various concentrations (10 μ g/mL, 20 μ g/mL, 40 μ g/mL, 60 μ g/mL, 80 μ g/mL,
100 μ g/mL), and test its UV-visible absorption spectrum；Fig. 2 b are the UV absorption light for the blank nano-carrier for not carrying medicine
Compose, its characterizing method is：By blank nano-carrier be diluted to various concentrations (20 μ g/mL, 40 μ g/mL, 60 μ g/mL, 80 μ g/mL,
100 μ g/mL), and test its uv-visible absorption spectra.Comparison diagram 2a and Fig. 2 b understand that tetradecyl alchohol is successfully loaded hollow general Shandong
Scholar indigo plant nano-particle it is hollow in, and cause its under identical mass concentration absworption peak reduction.
Embodiment 2
The present embodiment is prepared as follows carrying the nano-carrier of hydrophilic drugs：
(1) hollow prussian blue nano particle is prepared by the identical method of embodiment 1.
(2) 300mg tetradecyl alchohols are dissolved in the methanol solution of 6mL, 1mg/mL hydrophilic drugs adriamycin, stirred at 50 DEG C
To well mixed, mixed solution is obtained；The hollow prussian blue nano particles of 15mg are distributed in 3mL methanol solutions, received
Rice corpuscles re-suspension liquid；
(3) after mixing mixed solution and the nano-particle re-suspension liquid, 1h is stirred, makes part dissolved with tetradecyl alchohol and Ah mould
Element methanol solution enter hollow prussian blue nano particle it is hollow in；70 DEG C are then heated to, constant temperature stirring 4h makes hollow
Prussian blue nano inside particles and outside methanol solution volatilization are complete, obtain the medicament-carried nano being scattered in liquid tetradecyl alchohol
Support dispersion；
(4) continue constant temperature, and in medicament-carried nano support dispersion 90 DEG C of heating degree deionized water, stirring 30min；So
It is set as centrifuging on 40 DEG C of centrifuge in temperature afterwards, centrifugal rotational speed 13000r/min, centrifugation time 10min are taken
Carry the nano-carrier of hydrophilic drugs adriamycin；At room temperature, the tetradecyl alchohol solidification in medicament-carried nano carrier.
Fig. 3 a be the present embodiment carry the blank nano-carrier in nano-carrier and the embodiment 1 of hydrophilic drugs adriamycin with
And the ultra-violet absorption spectrum comparison diagram of free adriamycin, from the figure, it can be seen that in the range of 400-500nm, adriamycin has one
Individual absworption peak, while in the range of this, the absorption of medicament-carried nano carrier is accordingly improved, this shows that nano-carrier successfully carries medicine
Thing.
Fig. 4 is the thermogravimetric analysis figure of medicament-carried nano carrier obtained by hollow prussian blue nano particle and the present embodiment, its table
The method of levying is：After obtained nano-particle and medicament-carried nano carrier are freezed, using thermogravimetric analyzer, particle to be measured is placed in
Under air atmosphere, it is stepped up by room temperature to 400 DEG C, mass particle is measured in real time, as illustrated, hollow prussian blue nano grain
Protonatomic mass is smaller than the decline degree of medicament-carried nano carrier quality, shows that tetradecyl alchohol is removed from particle.
Fig. 5 a are the temperature rise effect figure of the medicament-carried nano carrier aqueous dispersions of various concentrations, and its characteristic manner is：3mL is taken to treat
Survey solution to irradiate in 808nm laser irradiation devices, irradiation time is that 10min, laser intensity are 2W, interval 10s records a temperature.
As a result illustrate with the rise of nano-carrier concentration, temperature rise effect increase.Fig. 5 b are the μ g/mL medicament-carried nano carrier water of concentration 150
The corresponding heating stability test figure of dispersion liquid, it can be seen that medicament-carried nano carrier has good photo and thermal stability.
Fig. 6 a are that the medicine of the obtained nano-carrier for carrying hydrophilic drugs adriamycin of the present embodiment at different temperatures is released
Curve is put, its characteristic manner is：Medicament-carried nano carrier is dissolved in deionized water (the μ g/mL of concentration 150), then takes 1mL to be placed in
In 5000Da bag filter, then bag filter is placed in 30mL deionized water, be heated to different temperatures (25 DEG C, 37 DEG C, 38
DEG C, 42 DEG C, 45 DEG C) and stir.It is solid when can be seen that tetradecyl alchohol below melting temperature from the change of release profiles, it is several
Medicine is not discharged, and temperature is reached after fusing point, tetradecyl alchohol liquefaction, starts a large amount of release medicines, illustrates that tetradecyl alchohol has good
Good temperature-responsive ability.
Fig. 7 a are medicine of the obtained nano-carrier for carrying hydrophilic drugs adriamycin of the present embodiment under interruption laser irradiation
Thing release profiles, its characteristic manner is：Medicament-carried nano carrier is dissolved in deionized water (the μ g/mL of concentration 150), 1mL is then taken
It is placed in centrifuge tube.Centrifuge tube is placed in 10min in the cell incubation case of 37 DEG C of constant temperature (laser pass) first, then 13000r/
Min centrifuges 5min, gathers supernatant and tests Cumulative release amount；Precipitation is resuspended as 1mL solution and 37 DEG C of constant temperature is placed in again
In cell incubation case, laser irradiation 5min (while with the control sample do not irradiated as a comparison) is opened, centrifuges and gathers again
Supernatant, test Cumulative release amount；Precipitation is resuspended again and is placed in 10min in the cell incubation case of 37 DEG C of constant temperature for 1mL solution
(laser pass).Repeat laser switch multiple.As a result indicating medicament-carried nano carrier has good light stimulus response medicine release
Ability.
Fig. 8 a are the load of blank nano-carrier and the present embodiment in adriamycin, the embodiment 1 of dissociating when being irradiated without laser
Medicine nano-carrier is to the fragmentation effect of HeLa cells, and Fig. 8 b are to HeLa cells by three during 808nm laser irradiation 5min
Fragmentation effect.As can be seen that when being irradiated without laser, free adriamycin has certain fragmentation effect to HeLa cells, but empty
The medicament-carried nano carrier of white nano-carrier and the present embodiment is to the injury very little of cell, then after laser irradiates, dissociate Ah mould
Element to the fragmentation effect of cell without significant changes, but blank nano-carrier and the present embodiment medicament-carried nano carrier to cell killing
The effect that effect is remarkably reinforced and caused more than free adriamycin, the fragmentation effect of medicament-carried nano carrier is better than blank nano-carrier
Fragmentation effect.
Embodiment 3
The present embodiment is prepared the nano-carrier for carrying medicine by the identical method of embodiment 2, is differed only in embodiment 2
In hydrophilic drugs adriamycin be changed to dewatering medicament camptothecine.
Fig. 3 b be the present embodiment carry the blank nano-carrier in nano-carrier and the embodiment 1 of dewatering medicament camptothecine with
And the ultra-violet absorption spectrum comparison diagram of free camptothecine, from the figure, it can be seen that in the range of 350-400nm, camptothecine has one
Individual absworption peak, while in the range of this, the absorption of medicament-carried nano carrier is accordingly improved, this shows that nano-carrier successfully carries medicine
Thing.
Fig. 6 b are that the medicine of the obtained nano-carrier for carrying dewatering medicament camptothecine of the present embodiment at different temperatures is released
Curve is put, its characteristic manner is：Medicament-carried nano carrier is dissolved in deionized water (the μ g/mL of concentration 150), then takes 1mL to be placed in
In 5000Da bag filter, then bag filter is placed in the aqueous solution of 30mL 0.1vt% Tween-80, is heated to not equality of temperature
Degree (25 DEG C, 37 DEG C, 38 DEG C, 42 DEG C, 45 DEG C) is simultaneously stirred.From release profiles change as can be seen that dewatering medicament release with
The release of hydrophilic drugs has identical trend, i.e., be all a large amount of releases after more than tetradecyl alchohol melting temperature, illustrate carrier
All there is the effect of stimuli responsive carrier to hydrophobe medicine.
Fig. 7 b are medicine of the obtained nano-carrier for carrying dewatering medicament camptothecine of the present embodiment under interruption laser irradiation
Thing release profiles, its characteristic manner is same as Example 1, and it is that medicament-carried nano carrier is dissolved in into telling for 0.1vt% to differ only in
In the aqueous solution of temperature -80.As a result indicating nano-carrier equally there is good light stimulus response medicine to discharge dewatering medicament
Ability.
Fig. 9 a are the load of blank nano-carrier and the present embodiment in camptothecine, the embodiment 1 of dissociating when being irradiated without laser
Medicine nano-carrier is to the fragmentation effect of HeLa cells, and Fig. 9 b are to HeLa cells by three during 808nm laser irradiation 5min
Fragmentation effect.As a result it can be seen that when being irradiated without laser, blank nano-carrier and load drug carrier are smaller to cell killing, and pass through
Fragmentation effect is much larger than free camplotheca acuminata after too drastic light irradiation, and medicament-carried nano carrier fragmentation effect is better than blank nano-carrier.
Claims (4)
1. based on hollow Prussian blue thermostimulation response type insoluble drug release nano-carrier, it is characterised in that：
The nano-carrier is using hollow prussian blue nano particle as shell mechanism, in the hollow middle filling of the shell mechanism
There is Thermo-sensitive material；The medicaments uniformity of required load is mixed in the Thermo-sensitive material, so as to constitute medicament-carried nano carrier；
Using the solid-liquid phase change phenomenon of the Thermo-sensitive material, the mode for realizing medicine response release is：Temperature sensitive less than described
Property material melting point temperature environment under, be mixed with the Thermo-sensitive material of medicine in the hollow prussian blue nano particle in solid
State, medicine does not discharge；When with outside stimulation in nano-carrier, the hollow prussian blue nano particle produces heat,
When the temperature of boring position is reached the Thermo-sensitive material melting point and the above, the Thermo-sensitive material of medicine is mixed with institute
State and be in a liquid state in hollow prussian blue nano particle, and from hollow prussian blue nano particle it is mesoporous from overflow, realize medicine
Release.
2. according to claim 1 based on hollow Prussian blue thermostimulation response type insoluble drug release nano-carrier, it is special
Levy and be：The Thermo-sensitive material is tetradecyl alchohol, paraffin, pentadecanol or tetradecylic acid.
3. according to claim 1 based on hollow Prussian blue thermostimulation response type insoluble drug release nano-carrier, it is special
Levy and be：The outside stimulus is the thermostimulation that light stimulus, microwave stimulation, magnetic stimulation, ultrasound stimulation or body heat trigger.
4. received in a kind of claims 1 to 3 described in any one based on hollow Prussian blue thermostimulation response type insoluble drug release
Meter Zai Ti preparation method, it is characterised in that comprise the following steps：
(1) hollow prussian blue nano particle is prepared by hydro-thermal method first；
(2) temperature-sensitive material and medicine are dissolved in volatile organic solvent, obtain mixed solution；By the hollow Prussia
Blue nano-particle is distributed in identical organic solvent, obtains nano-particle re-suspension liquid；
(3) after mixing the mixed solution and the nano-particle re-suspension liquid, stirring makes part dissolved with temperature-sensitive material and medicine
The organic solvent of thing enter hollow prussian blue nano particle it is hollow in；Then heat to the boiling point of the organic solvent with
On, constant temperature stirring, makes hollow prussian blue nano inside particles and outside organic solvent volatilization is complete, and acquisition is scattered in liquid
Medicament-carried nano support dispersion in temperature-sensitive material；
(4) continue constant temperature, and in the medicament-carried nano support dispersion heating degree be not less than Thermo-sensitive material melting point go from
Sub- water, stirring is then centrifuged for separation, obtains medicament-carried nano carrier；At room temperature, the temperature-sensitive material in the medicament-carried nano carrier
Solidification.
Priority Applications (1)
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Cited By (7)
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| CN107890566A (en) * | 2017-11-13 | 2018-04-10 | 北京大学 | A kind of diagnosing tumor treatment preparation and its preparation method and application |
| CN108355137A (en) * | 2018-02-08 | 2018-08-03 | 河南科技大学 | A kind of temperature sensitive phase transformation fatty alcohol mediates parents' drug delivery/controlled release carrier, preparation and its application |
| CN108785673A (en) * | 2018-07-06 | 2018-11-13 | 重庆医科大学 | A kind of Prussian blue similar object nanometer photo-thermal therapy agent of load medicine and preparation method thereof that sodium nitroprussiate is conjugated |
| CN109364253A (en) * | 2018-11-21 | 2019-02-22 | 南开大学 | One kind is for improving infiltrative nanoparticle of tumor tissues and its preparation method and application |
| CN110143617A (en) * | 2019-06-06 | 2019-08-20 | 复旦大学 | The preparation method of ultralight magnetic mesoporous nanometer frame |
| CN110215439A (en) * | 2019-07-15 | 2019-09-10 | 四川大学华西医院 | Based on hollow Prussian blue thermostimulation response type drug release nano-carrier and preparation method thereof |
| CN111632142A (en) * | 2020-06-24 | 2020-09-08 | 南方科技大学 | X-ray response-based drug release system and preparation method and application thereof |
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| CN107890566A (en) * | 2017-11-13 | 2018-04-10 | 北京大学 | A kind of diagnosing tumor treatment preparation and its preparation method and application |
| CN108355137A (en) * | 2018-02-08 | 2018-08-03 | 河南科技大学 | A kind of temperature sensitive phase transformation fatty alcohol mediates parents' drug delivery/controlled release carrier, preparation and its application |
| CN108785673A (en) * | 2018-07-06 | 2018-11-13 | 重庆医科大学 | A kind of Prussian blue similar object nanometer photo-thermal therapy agent of load medicine and preparation method thereof that sodium nitroprussiate is conjugated |
| CN108785673B (en) * | 2018-07-06 | 2021-04-13 | 重庆医科大学 | Sodium nitroprusside conjugated drug-loaded Prussian blue analogue nano photothermal therapeutic agent and preparation method thereof |
| CN109364253A (en) * | 2018-11-21 | 2019-02-22 | 南开大学 | One kind is for improving infiltrative nanoparticle of tumor tissues and its preparation method and application |
| CN110143617A (en) * | 2019-06-06 | 2019-08-20 | 复旦大学 | The preparation method of ultralight magnetic mesoporous nanometer frame |
| CN110215439A (en) * | 2019-07-15 | 2019-09-10 | 四川大学华西医院 | Based on hollow Prussian blue thermostimulation response type drug release nano-carrier and preparation method thereof |
| CN111632142A (en) * | 2020-06-24 | 2020-09-08 | 南方科技大学 | X-ray response-based drug release system and preparation method and application thereof |
| CN111632142B (en) * | 2020-06-24 | 2022-08-23 | 南方科技大学 | X-ray response-based drug release system and preparation method and application thereof |
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