CN1679518A - Magnetic medicinal capsules and preparation thereof - Google Patents
Magnetic medicinal capsules and preparation thereof Download PDFInfo
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- CN1679518A CN1679518A CN 200510023251 CN200510023251A CN1679518A CN 1679518 A CN1679518 A CN 1679518A CN 200510023251 CN200510023251 CN 200510023251 CN 200510023251 A CN200510023251 A CN 200510023251A CN 1679518 A CN1679518 A CN 1679518A
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Abstract
A magnetic medicinal capsule composed of core and shell for chemicotherapy of cancer features that its core is prepared from the chemicotherapeutic medicine and magnetic nanoparticles, and its multi-layer shell is prepared from the polyelectrolyte carrying opposite charges through alternative depositions. Its advantages are high medicine capacity, controllable slow release, and both magnetic and biologic targetings.
Description
Technical field
The present invention relates to a kind of magnetic medicinal capsules and preparation method thereof, particularly a kind of hud typed magnetic capsule that contains tumor chemotherapeutic drug and have control-release function, and its preparation method.
Background technology
Cancer is a kind of serious threat human life's a malignant tumor.Not only sickness rate height, and dangerous refractory, the mortality rate height.For the treatment cancer, adopt the chemotherapy means sometimes.During general cancer chemotherapy, chemotherapeutics acts on whole body, and lesion cancerous cell and whole body normal cell are all injured by chemotherapeutics.For this reason, people are attempting adding the method for magnetic material always in chemotherapeutics, make to contain the magnetic medicine.Like this, with this contain the magnetic medicine and inject blood vessel after, under enough strong external magnetic field guiding, optionally arrive and be positioned the tumor target area by blood vessel, realize the targeting dispenser, thereby improve curative effect, the attenuating toxic and side effects.
Chinese patent CN 1068199C (2001) Granted publication a kind of pastille microsphere and manufacture method thereof for the treatment of cancer.It is to make substrate by macromolecular material CAP, and it is the microsphere of 30～300 μ m that parcel anticarcinogen and magnetic material constitute particle diameter, adopts volatilization solvent method to make.Weak point is that microspherulite diameter is bigger, only is suitable for carrying out the treatment of the malignant tumor of feeding artery thromboembolism.
In order to bring into play drug action better on the cell of tumor tissues or subcellsular level, reducing pastille microsphere size is a kind of means.Chinese patent CN 1399958A (2003) discloses another kind of pastille magnetic target preparation and preparation method thereof.It is with the cancer therapy drug dissolving, adds the nanoscale magnetic fluid, adds emulsifying agent after fully mixing and makes pastille magnetic fluid emulsion.Again the medical high polymer monomer material is added emulsifying agent or make its high degree of dispersion with the method for solubilising.Add pastille magnetic fluid emulsion then, carry out monomer polymerization, make pastille magnetic millimicro ball or capsule (mean diameter 50～500nm).Yet the size of these magnetic target preparations can not fully be controlled, and the distribution of sizes of broad exists than big-difference contained magnetic material of each particle and medicament contg, causes the weak drug particle of magnetic, departs from the target area, the injury normal tissue cell.Medicine release in time simultaneously fails to be controlled.
Microcapsule with nucleocapsid structure can improve the drug level of target organ in order to the extended treatment time as medicament, improves curative effect, and lowers whole body blood drug level, effectiveness such as reduced toxicity.U.S. Pat 6,479,146 (2002) disclose the capsular method of a kind of self assembly of polyelectrolyte successively preparation micron.It is to make template with soluble micelle nuclear, and the alternating deposit polyelectrolyte is made novel three-dimensional lumen polymer shell.The thickness of shell is controlled by the cycle-index of alternating deposit, thus control drug release speed.The pattern of cavity particle depends on the pattern of template micelle, can obtain the polymer cavity of even size distribution.But do not relate to the problem that magnetic nanoparticle penetrates cyst wall, not as the magnetic anti-cancer drug preparation.
Summary of the invention
In order to solve problems of the prior art, it is capsule-core with chemotherapeutics and magnetic nanoparticle that the present invention proposes a kind of, and polyelectrolyte is the narrow diameter distribution that has of cyst wall, dispersibility, the magnetic medicinal capsules that controlled capability is good; And open its preparation method.
Technical scheme of the present invention is:
Magnetic medicinal capsules of the present invention is a kind of multiwalled hud typed capsule, it is characterized in that, described magnetic medicinal capsules comprises the kernel capsule-core that chemotherapeutics and magnetic nanoparticle constitute, and by the outer cyst wall of the nuclear that rete constituted of the polyelectrolyte alternating deposit of sandwich tape opposite charges.
Said chemotherapeutics is selected amycin, mitomycin, cisplatin, carboplatin, fluorouracil etc. for use, allly all can not select for use with the cancer therapy drug of magnetic nanoparticle and polyelectrolyte generation chemical reaction.Drug loading is 5～40%, and envelop rate is 60～93%.
Said magnetic nanoparticle can comprise the nanometer Fe of superparamagnetism
3O
4Particle, nanometer γ-Fe
2O
3Particle or mix transition metal such as chromium, cobalt, copper, magnesium, manganese, nickel, zinc and their mixture nanometer ferrite particle etc., only is nanometer Fe
3O
4Particle.The medicament capsule that contains magnetic nanoparticle can concentrate on the tumor target area rapidly under the guiding of outside magnetic field, helps treatment of cancer.Magnetic particle content is 0.5～50%.
The polyelectrolyte rete of said sandwich tape opposite charges is that anionic polyelectrolyte alternately constitutes sequence layer by one deck for cationic polyelectrolyte one deck.ABABAB for example, wherein A is a cationic polyelectrolyte, B is an anionic polyelectrolyte.The sequence number of plies is unrestricted.Cationic polyelectrolyte can be selected polymine (polyethyleneimine for use, PEI), diallyl dimethyl ammoniumchloride (poly (diallyldimethylammonium chloride), PDDA), the PAH hydrochlorate (poly (allylamine hydrochloride), PAH), polylysin (polylysine), chitosan (chitosan), gelatin (gelatin); Anionic polyelectrolyte can be selected poly-4-styrene sulfonate (poly (styrenesulfonate) for use, PSS), polyvinyl sulfuric acid salt (poly (vinylsulfate)), polyacrylic acid (poly (acrylic acid), PAA), dextran sulfate (dextran sulfate), sodium alginate (sodium alginate), heparin (heparin), DNA.
The preparation method of above-mentioned magnetic medicinal capsules comprises the steps:
1) nanometer Fe of superparamagnetism
3O
4The preparation of particle or other ferrite particle:
Certain amount of ammonia water or NaOH aqueous solution are slowly added FeCl
2With FeCl
3In the mixed liquor (or containing the iron salt of part transition metal salt), be 8～11, be preferably 10～11 until pH value with corresponding valence states of mole such as replacing.Then, stirred 0.5～5 hour down at 55～90 ℃.The mol ratio of bivalence and trivalent metal salt is 0.4～0.6.Obtain the nanometer Fe of particle diameter less than the superparamagnetism of 15nm
3O
4Particle or other ferrite particle suspension.Filter then, wash, obtain the nanometer Fe of superparamagnetism
3O
4Particle or other ferrite particle.
2) preparation of water solublity magnetic fluid:
The water solublity magnetic fluid is the nanometer Fe of superparamagnetism that step 1) is obtained
3O
4It is in 2～5 the weak acid solution that particle or other ferrite particle join pH, and as citric acid solution, ultra-sonic dispersion is mixed with that to contain magnetic nanoparticle be 0.5～10% water solublity magnetic fluid.
3) preparation of soluble template microsphere pipe absocped with polyelectrolyte on surface multilayer film:
Soluble template microsphere can be selected gelatine microsphere for use, melamino-formaldehyde (MF) microsphere, SiO
2Microsphere.The soluble template microsphere of selecting for use is that the mean diameter of single size is the microsphere of 0.05～10 μ m, and only is that mean diameter is the microsphere of 0.1～5 μ m.
The process of absorption polyelectrolyte multilayer film:
I) with the said yin, yang ion of technical scheme polyelectrolyte respectively and soluble-salt, be mixed with solution A and B as NaCl or KCl etc.The concentration of polyelectrolyte is 0.1～5g/L in the solution A (and B), and the concentration of salt is 0.05～0.6M.
Ii) with the said soluble template microsphere dispersed with stirring of technical scheme in solution A.Stir 5～60min under the room temperature, preferably 10～30min forms soluble template microsphere absorption water solubility of polyelectrolyte suspension, and the amount of polyelectrolyte must be greater than the amount of a monolayer of absorption on soluble template microsphere.The mass ratio of soluble template microsphere and suspension is 0.5～5%, is preferably 1～2%.Use centrifugally then, remove supernatant, with deionized water washing/centrifugal/disperse again 3～5 times.
Iii) with step I i) in obtain the deposit redispersion in solution B, and ii) ensuing set by step operation is carried out once again.
Iv) step I is obtained the deposit redispersion in solution A in ii), and ii) ensuing set by step operation is carried out once again.So circulation repeatedly obtains the complex microsphere suspension of soluble template microsphere pipe absocped with polyelectrolyte on surface multilayer film.
4) remove soluble template microsphere and make polyelectrolyte capsules:
I) remove the Soluble Gelatin microsphere and make the polyelectrolyte capsules step:
Get the gelatine microsphere suspension of the adsorption multi-layer polyelectrolyte film that step 3) makes, with acid as HCl or alkali such as NaOH adjusting pH value to 2～10, preferably 2～3, place 40～80 ℃ of water-baths, preferably 60 ℃ of water-baths, the dissolving gelatine microsphere, the dissolved gelatin of centrifugal removal, washing obtains polyelectrolyte cavity capsule.
Ii) remove solubility melamino-formaldehyde (MF) microsphere and make the polyelectrolyte capsules step:
Get the MF microsphere suspension liquid of the adsorption multi-layer polyelectrolyte film that step 3) makes, regulate pH value＜2 with acid as HCl, dissolving MF microsphere under the room temperature, the dissolved MF of centrifugal removal washes and obtains polyelectrolyte cavity capsule.
Iii) remove solubility SiO
2Microsphere is made the polyelectrolyte capsules step:
Get the SiO of the adsorption multi-layer polyelectrolyte film that step 3) makes
2Microsphere suspension liquid is regulated pH value＜2 with HF, or regulates pH value＞12 with alkali such as NaOH, dissolves SiO under the room temperature
2Microsphere, the dissolved SiO of centrifugal removal
2, washing obtains polyelectrolyte cavity capsule.
5) load tumor chemotherapeutic drug and nano magnetic material in the polyelectrolyte capsules:
Getting concentration that step 2 obtains and be 0.5～10% magnetic fluid, concentration is the chemotherapeutics of 100 μ g/m, and weight ratio is 1～5% the polyelectrolyte capsules suspension liquid of aqueous phase that is obtained by step 4, mix with 1: 5: 10 portion rate, use weak acid,, regulate pH value to 2～6 as citric acid, use strong electrolyte, as sodium chloride, regulate salinity between 0.1-1.0mol/L, be positioned over shaking table vibration 5～24h then.Utilize space features of smaller under the condition of polyelectrolyte multilayer film and pH value＞7 big in space under the condition of pH value＜7, after loading magnetic particle and chemotherapeutics, reuse is less than the filter membrane washing filtering of medicine-carrying capsule, to remove free magnetic particle and medicine, at this moment, the polyelectrolyte multilayer film space of the contraction release that can stop the outflow of magnetic particle and slow down medicine.Last lyophilization is standby.
The above-mentioned magnetic medicinal capsules that makes has following characteristics: (1) has selected for use uniform solubility microsphere to make template, and therefore the magnetic medicinal capsules size that obtains is more even; (2) the magnetic medicinal capsules size can be made template by the solubility microsphere of selecting different size for use, and the kind and the number of plies of absorption polyelectrolyte are controlled; (3) the magnetic medicinal capsules wall have under the condition of pH slant acidity the space big and under the nearly neutral condition of pH value the space less; The cyst wall structure is looser under the condition of higher salt concentrations, and the space is big, and the cyst wall structure is tightr under than the condition of low salt concn, the characteristics that the space is little.Under acid condition, load big magnetic particle and chemotherapeutics under the higher salt concentrations condition, pH is near neutral and discharge medicine down than low-salt conditions, therefore has the magnetic of carrying and medication amount big, and the slow characteristics of drug release when using; (4) select for use the different types of polyelectrolyte and the absorption number of plies can control drug release speed; (5) select for use the salinity of varying environment and the pH value can control drug release speed; (6) Biao Mian polyelectrolyte has stronger functionally, and better to various aqueous solution dispersibility, the active substances of can delivering a child as antibody, antigen, enzyme, protein or nucleic acid, thereby can be realized two targeting purposes of magnetic targeting and biological targeting simultaneously.
The specific embodiment
Further illustrate content of the present invention below in conjunction with embodiment, but these embodiment do not limit protection scope of the present invention.
Embodiment 1
Step (1) slowly adds 1.0mol/L NaOH aqueous solution the FeCl of 1.0mol/L
2FeCl with 2.0mol/L
3In the mixed aqueous solution, be 10 until pH value.Stir 1h down at 85 ℃ then, obtain the nanometer Fe of superparamagnetism
3O
4Particle suspension.Filter washing then.Observe Fe with transmission electron microscope (TEM)
3O
4The particle diameter of particle is 8～12nm.With the nanometer Fe that makes
3O
4It is 3 citric acid solution that particle joins pH, and ultra-sonic dispersion is mixed with that to contain magnetic nanoparticle be 2% water solublity magnetic fluid.
The gelatine microsphere that takes by weighing the 2g mean diameter and be 300nm is poured in the small beaker of 500mL.
Step (2) adds poly-4-styrene sulfonate (PSS) (the containing 0.5M NaCl) aqueous solution of anionic polyelectrolyte that 100mL concentration is 1g/L.Be positioned over shaking table vibration 20min under the room temperature.With centrifuge centrifugal 15min under 5000 rotating speeds that change.Remove supernatant.With deionized water washing/centrifugal/disperse again 4 times, obtain adsorbing the microsphere of one deck PSS.
Step (3) adds cationic polyelectrolyte PAH hydrochlorate (PAH) (the containing 0.5M NaCl) aqueous solution that 100mL concentration is 1g/L again.Be positioned over shaking table vibration 20min under the room temperature, use centrifugally then, remove supernatant,, obtain the microsphere that PAH is adsorbed on the second layer with deionized water washing/centrifugal/disperse again 4 times.
Step (4) is repeating step 2 constantly), 3), obtain the gelatine microsphere outside at last and be the PSS adsorption layer for first and third, five, seven layer, second, four, six, eight layer is the PAH adsorption layer.
Step (5) is regulated pH value to 3 with the gelatine microsphere suspension of the adsorption multi-layer polyelectrolyte film that makes with HCl, places 60 ℃ of water-baths, the dissolving gelatine microsphere, and the dissolved gelatin of centrifugal removal, washing obtains polyelectrolyte cavity capsule.
Step (6) is got gained magnetic fluid 1ml (concentration is 1%), chemotherapeutics amycin 10ml concentration is 100 μ g/ml, join the 5ml weight ratio together and be in 2% the polyelectrolyte capsules suspension liquid of aqueous phase that obtains by embodiment 6, use citric acid, regulate pH value to 3, add NaCl, concentration is 0.5mol/L.Be positioned over shaking table vibration 24h then.Utilize polyelectrolyte multilayer film bigger characteristic in space in the saline solution of pH slant acidity, behind loading magnetic particle and the chemotherapeutics, the reuse aperture is the microporous filter membrane washing filtering of 0.8 μ m, and to remove free magnetic particle and medicine, lyophilization is standby.Recording the drug loading of amycin in polyelectrolyte capsules with ultraviolet spectrophotometer at amycin characteristic absorption wavelength place is 31.68%, and envelop rate is 91.86%.The magnetic content that utilizes thermogravimetric analysis to record in the capsule that pastille contains magnetic is 21.6%.
Step 7) will obtain contains the polyelectrolyte capsules 0.5g that magnetic contains amycin, joins in the sustained-release liquid.Sustained-release liquid is used citric acid in advance, regulates pH value to 3, and contains the NaCl that concentration is 0.6mol/L.Be positioned over the shaking table vibration then.Utilize the characteristic that has the space between polyelectrolyte multilayer film to realize the slow release of chemotherapeutics, at amycin characteristic absorption wavelength place, follow the trail of at different time point places by capsule and be discharged into amycin amount in the sustained-release liquid with ultraviolet spectrophotometer.The amycin rate of disengaging in the capsule reaches 50% needs 14 hours, and the cumulative release rate will need through 66 hours approximately above 90%.
Embodiment 2
With mean diameter is that melamino-formaldehyde (MF) microsphere of 2 μ m replaces the gelatine microsphere among the embodiment 1, replace PAH hydrochlorate (PAH) with cationic polyelectrolyte diallyl dimethyl ammoniumchloride (PDDA), with " to regulate pH value be 1.5 to HCl; dissolving MF microsphere under the room temperature " in the step of replacing (4) " regulate pH value to 3 with HCl; place 60 ℃ of water-baths ", all the other repeat the 2nd～6 step among the embodiment 1, obtain first and third, five, seven layer at last and be the PSS adsorption layer, second, four, six, eight layer is the magnetic medicinal capsules of PDDA adsorption layer.
Get the polyelectrolyte capsules 0.5g that magnetic contains amycin that contains of gained, drug loading is 30.94%, and envelop rate is 92.42%.Use the method with embodiment 1 then, except pH value in the sustained-release liquid is 5, NaCl concentration is outside the 0.3mol/L, carries out the slow release of cancer therapy drug.The amycin rate of disengaging in the capsule reaches 50% needs 19 hours, and the cumulative release rate will need through 85 hours approximately above 90%.
Embodiment 3
With mean diameter is the SiO of 100nm
2Microsphere replaces the gelatine microsphere among the embodiment 2, replaces poly-4-styrene sulfonate (PSS) with anionic polyelectrolyte polyacrylic acid (PAA), with " NaOH adjusting pH value is 13, dissolves SiO under the room temperature
2Microsphere " replacement " regulate pH value to 3 with HCl, place 60 ℃ of water-baths ", the 2nd～6 step that all the other repeat among the embodiment 1 obtains first and third, five, seven layer at last and is the PAH adsorption layer, and second, four, six, eight layer is the magnetic medicinal capsules of PAA adsorption layer.
Get the polyelectrolyte capsules 0.5g that magnetic contains amycin that contains that embodiment 1 obtains, the pH value in sustained-release liquid is 6, and all the other methods are with embodiment 1.The amycin rate of disengaging in the capsule reaches 50% needs 18 hours, and the cumulative release rate will need through 82 hours approximately above 90%.
Embodiment 4
Except with " to regulate pH value be 1 to HF " replace among the embodiment 3 " to regulate pH value with NaOH be 13 ", repeat embodiment 3, obtain first and third, five, seven layer and be the PAH adsorption layer, second, four, six, eight layer is the magnetic medicinal capsules of PAA adsorption layer.
Get the polyelectrolyte capsules 0.5g that magnetic contains amycin that contains that embodiment 2 obtains, except NaCl concentration was 0.9mol/L, all the other methods were with embodiment 1.The amycin rate of disengaging in the capsule reaches 50% needs 15 hours, and the cumulative release rate will need through 78 hours approximately above 90%.
Embodiment 5
Except replace the amycin among the embodiment 3 with mitomycin, outside the PAA among the sodium alginate replacement embodiment 3, repeat embodiment 3, obtain first and third, five, seven layer and be the PAH adsorption layer, second, four, six, eight layer is the magnetic medicinal capsules of sodium alginate adsorption layer.
Repeat step (6) and (7) among the embodiment 1, the drug loading that records the mitomycin in the capsule is 27.76%, and envelop rate is 86.95%.The mitomycin rate of disengaging reaches 50% needs 13 hours, and the cumulative release rate will need through 69 hours approximately above 90%.
Comparative Examples
Getting the aqueous solution 10mL that contains amycin 100 μ g/mL, put into bag filter, is 5 bag filter being placed pH value, and NaCl concentration is in the sustained-release liquid of 0.9mol/L, is positioned over the shaking table vibration then.Detection method is with embodiment 10.Amycin discharges 50% to be needed about 24min, and the release rate of amycin surpasses 90% after 3 hours.
Claims (6)
1, a kind of magnetic medicinal capsules, it is a kind of multiwalled hud typed capsule, it is characterized in that described magnetic medicinal capsules comprises the kernel capsule-core that is made of chemotherapeutics and magnetic nanoparticle, and by the outer cyst wall of the nuclear that rete constituted of the polyelectrolyte alternating deposit of sandwich tape opposite charges.
2, magnetic medicinal capsules as claimed in claim 1 is characterized in that, chemotherapeutics is wherein selected the cancer therapy drug that chemical reaction does not take place with magnetic nanoparticle and polyelectrolyte for use, and drug loading is 5～40%, and envelop rate is 60～93%; Magnetic nanoparticle wherein is the nanometer ferrite particle of superparamagnetism, and magnetic particle content is 0.5～50%.
3, magnetic medicinal capsules as claimed in claim 2 is characterized in that, magnetic nanoparticle wherein is a nanometer Fe
3O
4Particle.
4, magnetic medicinal capsules as claimed in claim 1 is characterized in that, the polyelectrolyte rete of the outer cyst wall of described formation nuclear alternately constitutes sequence layer by the zwitterion polyelectrolyte, and its sequence number of plies is unrestricted.
5, a kind of preparation method of magnetic medicinal capsules is characterized in that, comprises the steps:
1) nanometer Fe of superparamagnetism
3O
4The preparation of particle or other ferrite particle:
Certain amount of ammonia water or NaOH aqueous solution are slowly added FeCl
2With FeCl
3Mixed liquor or contain the part transition metal salt etc. the mole corresponding valence state iron salt in, until pH value is 8～11, stirred 0.5～5 hour down at 55～90 ℃, the mol ratio of bivalence and trivalent metal salt is 0.4～0.6, obtains the nanometer Fe of particle diameter less than the superparamagnetism of 15nm
3O
4Particle or other ferrite particle suspension refilter, wash, and obtain the nanometer Fe of superparamagnetism
3O
4Particle or other ferrite particle;
2) preparation of water solublity magnetic fluid:
The nanometer Fe of the superparamagnetism that step 1) is obtained
3O
4It is in 2～5 the weak acid solution that particle or other ferrite particle join pH, through ultra-sonic dispersion, is mixed with that to contain magnetic nanoparticle be 0.5～10% water solublity magnetic fluid;
3) preparation soluble template microsphere pipe absocped with polyelectrolyte on surface multilayer film:
Selecting the mean diameter of single size for use is the soluble template microsphere of 0.05～10 μ m, produces the complex microsphere suspension of soluble template microsphere pipe absocped with polyelectrolyte on surface multilayer film;
4) remove soluble template microsphere and make polyelectrolyte capsules;
5) load tumor chemotherapeutic drug and nano magnetic material in the polyelectrolyte capsules:
Getting concentration that step 2 obtains and be 0.5～10% magnetic fluid, concentration is the chemotherapeutics of 100 μ g/m, and weight ratio is 1～5% polyelectrolyte capsules suspension liquid of aqueous phase, mix with 1: 5: 10 portion rate, regulate pH value to 2～6 with weak acid, use strong electrolyte, regulate salinity between 0.1-1.0mol/L, be positioned over shaking table vibration 5～24h then, load magnetic particle and chemotherapeutics; Reuse is less than the filter membrane washing filtering of medicine-carrying capsule, lyophilization.
6, magnetic medicinal capsules preparation method as claimed in claim 5 is characterized in that pH value is adjusted to 10～11 in the step 1), and soluble template microsphere is gelatine microsphere, melamino-formaldehyde (MF) microsphere, SiO in the step 3)
2In the microsphere any, mean diameter is 0.1～5 μ m.
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|---|---|---|---|
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1973832B (en) * | 2006-10-24 | 2010-05-12 | 中山大学 | Biodegradable nanometer medicine capsule with CT trace effect and its preparation process |
| CN1943565B (en) * | 2006-10-24 | 2010-05-26 | 中山大学 | Biological degradable nano medicinal capsule with MRI tracer effect and its preparing method |
| CN101396351B (en) * | 2007-09-28 | 2011-04-27 | 上海交通大学医学院附属瑞金医院 | Drug-loaded polyelectrolyte capsules in response to phosphatase concentration and preparation method thereof |
| US20150125879A1 (en) * | 2013-09-25 | 2015-05-07 | Massachusetts Institute Of Technology | Biodegradable Layer-by-Layer (LbL) Films for Cell Capture and Release |
| CN105161246A (en) * | 2015-08-21 | 2015-12-16 | 盐城工学院 | Nickel-zinc ferrite/polyacrylic acid nano-composite material and preparation method thereof |
| CN107260703A (en) * | 2017-05-02 | 2017-10-20 | 北京理工大学 | A kind of internal magnetic guiding delivering method of salmonella |
| US10278927B2 (en) | 2012-04-23 | 2019-05-07 | Massachusetts Institute Of Technology | Stable layer-by-layer coated particles |
| US11419947B2 (en) | 2017-10-30 | 2022-08-23 | Massachusetts Institute Of Technology | Layer-by-layer nanoparticles for cytokine therapy in cancer treatment |
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2005
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Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1973832B (en) * | 2006-10-24 | 2010-05-12 | 中山大学 | Biodegradable nanometer medicine capsule with CT trace effect and its preparation process |
| CN1943565B (en) * | 2006-10-24 | 2010-05-26 | 中山大学 | Biological degradable nano medicinal capsule with MRI tracer effect and its preparing method |
| CN101396351B (en) * | 2007-09-28 | 2011-04-27 | 上海交通大学医学院附属瑞金医院 | Drug-loaded polyelectrolyte capsules in response to phosphatase concentration and preparation method thereof |
| US10278927B2 (en) | 2012-04-23 | 2019-05-07 | Massachusetts Institute Of Technology | Stable layer-by-layer coated particles |
| US20150125879A1 (en) * | 2013-09-25 | 2015-05-07 | Massachusetts Institute Of Technology | Biodegradable Layer-by-Layer (LbL) Films for Cell Capture and Release |
| CN105161246A (en) * | 2015-08-21 | 2015-12-16 | 盐城工学院 | Nickel-zinc ferrite/polyacrylic acid nano-composite material and preparation method thereof |
| CN105161246B (en) * | 2015-08-21 | 2017-05-10 | 盐城工学院 | Nickel-zinc ferrite/polyacrylic acid nano-composite material and preparation method thereof |
| CN107260703A (en) * | 2017-05-02 | 2017-10-20 | 北京理工大学 | A kind of internal magnetic guiding delivering method of salmonella |
| US11419947B2 (en) | 2017-10-30 | 2022-08-23 | Massachusetts Institute Of Technology | Layer-by-layer nanoparticles for cytokine therapy in cancer treatment |
| US11964026B2 (en) | 2017-10-30 | 2024-04-23 | Massachusetts Institute Of Technology | Layer-by-layer nanoparticles for cytokine therapy in cancer treatment |
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