CN103655484B - A kind ofly utilize self-assembling technique method preparing taxol slow release microballoons and products thereof - Google Patents
A kind ofly utilize self-assembling technique method preparing taxol slow release microballoons and products thereof Download PDFInfo
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Abstract
The present invention relates to and a kind ofly utilize self-assembling technique method preparing taxol slow release microballoons and products thereof, described method comprises: prepare chitosan microball self assembly template, utilize the electrostatic interaction between the different electric charge polyelectrolyte of band, sodium sulfate glucosan and chitosan self assembly are formed composite drug carried microsphere on chitosan microball surface.Owing to adopting ultrasonic emulsification means in conjunction with specific oil phase in paclitaxel composite drug carried microsphere preparation of the present invention, therefore the microsphere obtained is in the spherical morphology of rule, and reach Nano Particle, have higher clad ratio, extracorporeal releasing test shows to have good slow release effect.Preparation technology's cost of this paclitaxel composite drug carried microsphere is low, simple to operate, easily repeats, and controllability is good, has application prospect well.
Description
Technical field
The present invention relates to coated paclitaxel carried medicine microsphere of a kind of method utilizing self-assembling technique to prepare taxol slow release microballoons, particularly a kind of Biodegradable polymer material and preparation method thereof.
The invention still further relates to the taxol slow release microballoons that said method obtains.
Background technology
Paclitaxel (PTX) extracts the natural anticancer medical obtained from the trunk and bark of Pacific Ocean Chinese yew genus plants yew, is mainly used in the treatment of ovarian cancer, breast carcinoma, cancer of pancreas, gastric cancer, pulmonary carcinoma, brain and tumor colli clinically.Because its dissolubility in water is less than 1 μ g/mL, many by polyoxyethylene castor oil (Cremophor EL) and dehydrated alcohol (50:50 clinically at present, v/v) form, use front normal saline or glucose solution dilution 5-20 doubly, although add the dissolubility of medicine to a certain extent, but after administration there is the untoward reaction such as serious anaphylaxis, nephrotoxicity, neurotoxicity, cardiac toxicity, hypotension in patient, makes its clinical practice be restricted.To not containing polyoxyethylene castor oil, and the research that can improve other preparations of PTX bioavailability becomes current study hotspot, in recent years, studies have found that the applied defect selecting suitable carrier can improve and solve paclitaxel.
Wherein, report that maximum is be that carrier prepares microball preparation with polylactide and its copolymer.He TX solvent evaporated method is prepared PLLA and is carried paclitaxel mono-dispersion microballoon, this microsphere improves the bioavailability of medicine and extends pharmaceutical release time, but exist to dash forward at beginning 3h and release phenomenon (MicrofluidNanofluid, 2011,10:1289).Xue Jing adopts emulsification-evaporation method PLGA to wrap up paclitaxel, prepared the drug-carrying nanometer particle of particle diameter 217.6nm by orthogonal test, drug loading only has 1.79%, and has obvious dashing forward to release phenomenon (Chinese Tissue Engineering Study and clinical rehabilitation, 2010,14:7824).KangYQ supercritical fluid technology has been prepared PLLA and has been carried paclitaxel microsphere, microsphere is that ellipse spherical surface is very smooth, but particle size distribution is uneven, and the carrying drug ratio of microsphere is lower by 14.33%, microsphere exists to dash forward in front 30min releases phenomenon (Langmuir2008,24:7432).
All there is the prominent of release initial stage in the report of above-mentioned paclitaxel carried medicine microsphere and release problem, may cause the blood drug level in human body close to or exceed toxic level, produce obvious toxic and side effects.And microspherulite diameter of the prior art is comparatively large, and wider distribution, effective ingredient can not be discharged for a long time.
Layer one deck self-assembling technique is the method utilizing successively alternating deposit, by the intermolecular weak interaction of each layer (as electrostatic attraction, hydrogen bond, coordinate bond etc.), layer and layer are spontaneously associated and forms structural integrity, stable performance, there is the molecule aggregate of certain specific function or the process of supramolecular structure, the remarkable superiority of the method for the preparation of medicine carrying microballoons is to control accurately the size of microsphere, composition, structure, form and wall thickness on nanoscale.And due to its charge effect in self-assembling technique, cause the dispersion of material often to go wrong, therefore may cause potential reunion thus make the microspherulite diameter of preparation comparatively large, disperseing uneven.
Summary of the invention
The present invention completes to solve above-mentioned deficiency of the prior art, and the object of this invention is to provide a kind of method that self-assembling technique prepares taxol slow release microballoons, it utilizes self-assembling technique to prepare medicine carrying microballoons, and realizes the controlled slow releasing of medicine.Efficiently solve the release initial stage of paclitaxel carried medicine microsphere in prior art prominent release cause blood in human body in concentration close to or exceed toxic level, produce the problem of obvious toxic-side effects.Simultaneously the present invention adopts ultrasonic emulsification means, and chooses the microsphere that specific oil phase makes finally to obtain and have Nano Particle, and even particle size distribution.The present invention simultaneously also provides said method preparation-obtained taxol slow release microballoons.
Technical scheme of the present invention is as described below:
The present invention utilizes self-assembling technique to prepare the method for taxol slow release microballoons, it is characterized in that comprising the following steps:
1) preparation of self assembly template:
Step 1: take 0.025g-0.01g chitosan, joins in the dilute acid soln of 10mL, is stirred to chitosan and dissolves completely, then adds 0.0025g-0.01g taxol drug as aqueous phase; Measure the liquid paraffin of 25ml-125mL as oil phase;
Step 2: aqueous phase is instilled in oil phase, then ultrasonic emulsification 1-2min, obtain finely dispersed water-in-oil emulsion, instill the glutaraldehyde solution of the concentration 37wt% of 1-2mL again, Keep agitation 30-40min, make its full cross-linked rear centrifugalize, precipitate petroleum ether three final vacuum lyophilizations 12 hours, obtain positively charged chitosan drug-loading microsphere; And it can be used as the template of following self assembling process;
2) self assembly taxol slow release microballoons preparation:
Step 3: above-mentioned positively charged chitosan drug-loading microsphere is placed in the polyanion sodium sulfate glucosan acetic acid solution that 10mL concentration is 2wt%, centrifugalize cleaning after sonic oscillation 30min at 25 DEG C; The electrostatic attraction effect self assembly between the polyelectolyte material of two kinds of oppositely chargeds is utilized to form the first tunic outside this template microsphere;
Step 4: obtain taxol slow release microballoons after again repeating above-mentioned steps 3 twice postlyophilization, the mean diameter of described microsphere is about 200nm-700nm.
The described self-assembling technique that utilizes prepares the method for taxol slow release microballoons, it is characterized in that: described dilute acid soln is selected from acetic acid, formic acid or propanoic acid, and its concentration is 1wt%.
The described self-assembling technique that utilizes prepares the method for taxol slow release microballoons, it is characterized in that: described microsphere average grain diameter is about 300nm-600nm.
The taxol slow release microballoons that the present invention also provides a kind of said method to prepare.
In self assembling process of the present invention, step 3 can carry out multilamellar self assembly according to actual needs, to regulate its rate of release.The more convenient particulate vector for designing different demand.
In the present invention if no special instructions, all percentage ratio is all weight percentage.
The taxol slow release microballoons prepared due to the present invention is outer at the coated multilamellar sodium sulfate glucosan of chitosan drug-loading microsphere surface, and therefore taxol slow release microballoons of the present invention is a kind of paclitaxel composite drug carried microsphere, and it has core-shell structure.
Self assembly principle of the present invention is as follows: because chitosan is a kind of natural macromolecule amylose of positively charged, the electrostatic force between the sodium sulfate glucosan of its oppositely charged is utilized in the present invention, acted in medicine carrying microballoons template by self assembly and form multilayer film, thus make the paclitaxel being adsorbed on microsphere top layer weak link coated further, the initial release speed of medicine can be reduced, reduce toxic and side effects, improve the safety in utilization of medicine.
Accompanying drawing explanation
Fig. 1 is the electron micrograph after the paclitaxel composite drug carried microsphere finished product lyophilizing of the embodiment of the present invention 5.
Fig. 2 is the paclitaxel composite drug carried microsphere of the embodiment of the present invention 8 and the In-vitro release curves of chitosan drug-loading microsphere under 37 DEG C of conditions of comparative example 1.
Detailed description of the invention
Below in conjunction with embodiment and comparative example, the present invention is described in detail, and following embodiment is only used for the detailed explanation to description, not as restriction of the present invention.
Embodiment 1
Taking 0.025g chitosan, to add 10mL concentration be in 1% acetic acid solution, be stirred to dissolving, add 0.025g taxol drug as aqueous phase, instilled in 25mL liquid paraffin, ultrasonic emulsification 2min, adds 1mL glutaraldehyde under magnetic stirring, crosslinked end after 30min, 2500rpm centrifugalize, precipitate petroleum ether three final vacuum lyophilization 12h obtain chitosan drug-loading microsphere.Being added 10mL concentration is in the sodium sulfate glucosan acetic acid solution of 2%, adds the chitosan acetic acid solution that 10ml concentration is 2% at 25 DEG C after sonic oscillation 30min after centrifugalize cleaning.In the product obtained, again add 10ml concentration is in the sodium sulfate glucosan acetic acid solution of 2%, adds the chitosan acetic acid solution that 10ml concentration is 2% at 25 DEG C after sonic oscillation 30min after centrifugalize cleaning.In the product obtained, again again add 10ml concentration is in the sodium sulfate glucosan acetic acid solution of 2%, add the chitosan acetic acid solution that 10ml concentration is 2% after centrifugalize cleaning after sonic oscillation 30min at 25 DEG C, obtaining faint yellow white powder after lyophilization is composite drug carried microsphere.Adopt the particle diameter of Zano ZS laser particle analyzer test microsphere, adopt the absorbance of ultraviolet spectrophotometer testing drug, according to its encapsulation rate of formulae discovery, the results are shown in Table 1.
Embodiment 2
Taking 0.025g chitosan, to add 10ml concentration be in 1% acetic acid solution, be stirred to dissolving, add 0.025g taxol drug as aqueous phase, instilled in 75ml liquid paraffin, ultrasonic emulsification 2min, adds 1m1 glutaraldehyde under magnetic stirring, crosslinked end after 30min, 2500rpm centrifugalize, precipitate petroleum ether three final vacuum lyophilization 12h obtain chitosan drug-loading microsphere.Being added 10ml concentration is in the sodium sulfate glucosan acetic acid solution of 2%, adds the chitosan acetic acid solution that 10ml concentration is 2%, repeat said process twice at 25 DEG C after sonic oscillation 30min after centrifugalize cleaning.Obtaining faint yellow white powder after lyophilization is composite drug carried microsphere.Adopt the particle diameter of Zano ZS laser particle analyzer test microsphere, adopt the absorbance of ultraviolet spectrophotometer testing drug, according to its encapsulation rate of formulae discovery, the results are shown in Table 1.
Embodiment 3
Taking 0.025g chitosan, to add 10ml concentration be in 1% acetic acid solution, be stirred to dissolving, add 0.025g taxol drug as aqueous phase, instilled in 125ml liquid paraffin, ultrasonic emulsification 2min, adds 1ml glutaraldehyde under magnetic stirring, crosslinked end after 30min, 2500rpm centrifugalize, precipitate petroleum ether three final vacuum lyophilization 12h obtain chitosan drug-loading microsphere.Being added 10ml concentration is in the sodium sulfate glucosan acetic acid solution of 2%, adds the chitosan acetic acid solution that 10ml concentration is 2%, repeat said process twice at 25 DEG C after sonic oscillation 30min after centrifugalize cleaning.Obtaining faint yellow white powder after lyophilization is composite drug carried microsphere.Adopt the particle diameter of Zano ZS laser particle analyzer test microsphere, adopt the absorbance of ultraviolet spectrophotometer testing drug, according to its encapsulation rate of formulae discovery, the results are shown in Table 1.
Embodiment 4
Taking 0.025g chitosan, to add 10ml concentration be in 1% acetic acid solution, be stirred to dissolving, add 0.025g taxol drug as aqueous phase, instilled in 25ml liquid paraffin, ultrasonic emulsification lmin, adds 1ml glutaraldehyde under magnetic stirring, crosslinked end after 30min, 2500rpm centrifugalize, precipitate petroleum ether three final vacuum lyophilization 12h obtain chitosan drug-loading microsphere.Being added 10ml concentration is in the sodium sulfate glucosan acetic acid solution of 2%, adds the chitosan acetic acid solution that 10ml concentration is 2%, repeat said process twice at 25 DEG C after sonic oscillation 30min after centrifugalize cleaning.Obtaining faint yellow white powder after lyophilization is composite drug carried microsphere.Adopt the particle diameter of Zano ZS laser particle analyzer test microsphere, adopt the absorbance of ultraviolet spectrophotometer testing drug, according to its encapsulation rate of formulae discovery, the results are shown in Table 1.
Embodiment 5
Taking 0.1g chitosan, to add 10ml concentration be in 1% acetic acid solution, be stirred to dissolving, add 0.025g taxol drug as aqueous phase, instilled in 25ml liquid paraffin, ultrasonic emulsification 2min, adds 1ml glutaraldehyde under magnetic stirring, crosslinked end after 30min, 2500rpm centrifugalize, precipitate petroleum ether three final vacuum lyophilization 12h obtain chitosan drug-loading microsphere.Being added 10ml concentration is in the sodium sulfate glucosan acetic acid solution of 2%, adds the chitosan acetic acid solution that 10ml concentration is 2%, repeat said process twice at 25 DEG C after sonic oscillation 30min after centrifugalize cleaning.Obtaining faint yellow white powder after lyophilization is composite drug carried microsphere.Adopt the particle diameter of Zano ZS laser particle analyzer test microsphere, adopt the absorbance of ultraviolet spectrophotometer testing drug, according to its encapsulation rate of formulae discovery, the results are shown in Table 1.
Embodiment 6
Taking 0.05g chitosan, to add 10ml concentration be in 1% acetic acid solution, be stirred to dissolving, add 0.025g taxol drug as aqueous phase, instilled in 25ml liquid paraffin, ultrasonic emulsification 2min, adds 1ml glutaraldehyde under magnetic stirring, crosslinked end after 30min, 2500rpm centrifugalize, precipitate petroleum ether three final vacuum lyophilization 12h obtain chitosan drug-loading microsphere.Being added 10ml concentration is in the sodium sulfate glucosan acetic acid solution of 2%, adds the chitosan acetic acid solution that 10ml concentration is 2%, repeat said process twice at 25 DEG C after sonic oscillation 30min after centrifugalize cleaning.Obtaining faint yellow white powder after lyophilization is composite drug carried microsphere.Adopt the particle diameter of Zano ZS laser particle analyzer test microsphere, adopt the absorbance of ultraviolet spectrophotometer testing drug, according to its encapsulation rate of formulae discovery, the results are shown in Table 1.
Embodiment 7
Taking 0.025g chitosan, to add 10ml concentration be in 1% acetic acid solution, be stirred to dissolving, add 0.025g taxol drug as aqueous phase, instilled in 50ml liquid paraffin, ultrasonic emulsification 2min, adds 2ml glutaraldehyde under magnetic stirring, crosslinked end after 45min, 2500rpm centrifugalize, precipitate petroleum ether three final vacuum lyophilization 12h obtain chitosan drug-loading microsphere.Being added 10ml concentration is in the sodium sulfate glucosan acetic acid solution of 2%, adds the chitosan acetic acid solution that 10ml concentration is 2%, repeat said process twice at 25 DEG C after sonic oscillation 30min after centrifugalize cleaning.Obtaining faint yellow white powder after lyophilization is composite drug carried microsphere.Adopt the particle diameter of Zano ZS laser particle analyzer test microsphere, adopt the absorbance of ultraviolet spectrophotometer testing drug, according to its encapsulation rate of formulae discovery, the results are shown in Table 1.
Embodiment 8
Taking 0.05g chitosan, to add 10ml concentration be in 1% acetic acid solution, be stirred to dissolving, add 0.0lg taxol drug as aqueous phase, instilled in 50ml liquid paraffin, ultrasonic emulsification 2min, adds 1ml glutaraldehyde under magnetic stirring, crosslinked end after 45min, 2500rpm centrifugalize, precipitate petroleum ether three final vacuum lyophilization 12h obtain chitosan drug-loading microsphere.Being added 10ml concentration is in the sodium sulfate glucosan acetic acid solution of 2%, adds the chitosan acetic acid solution that 10ml concentration is 2%, repeat said process twice at 25 DEG C after sonic oscillation 30min after centrifugalize cleaning.Obtaining faint yellow white powder after lyophilization is composite drug carried microsphere.Adopt the particle diameter of Zano ZS laser particle analyzer test microsphere, adopt the absorbance of ultraviolet spectrophotometer testing drug, according to its encapsulation rate of formulae discovery, the results are shown in Table 1.
Comparative example 1 (chitosan drug-loading microsphere): adopt non-self-assembling technique to equip chitosan drug-loading microsphere.
Taking 0.025g chitosan, to add 10ml concentration be in 1% acetic acid solution, be stirred to dissolving, add 0.025g taxol drug as aqueous phase, instilled in 25ml liquid paraffin, ultrasonic emulsification 2min, adds 1ml glutaraldehyde under magnetic stirring, crosslinked end after 30min, 2500rpm centrifugalize, precipitate petroleum ether three final vacuum lyophilization 12h obtain chitosan drug-loading microsphere.The particle diameter adopting ZanoZS laser particle analyzer to test this microsphere is 430.5nm, and adopting the absorbance of ultraviolet spectrophotometer testing drug, is 6.58% according to its encapsulation rate of formulae discovery.
Comparative example 2 (not adopting excusing from death emulsifying)
Taking 0.025g chitosan, to add 10ml concentration be in 1% acetic acid solution, be stirred to dissolving, add 0.025g taxol drug as aqueous phase, instilled in 25ml liquid paraffin, add 1ml glutaraldehyde under magnetic stirring, crosslinked end after 30min, 2500rpm centrifugalize, precipitate petroleum ether three final vacuum lyophilization 12h obtain chitosan drug-loading microsphere.Being added 10ml concentration is in the sodium sulfate glucosan acetic acid solution of 2%, adds the chitosan acetic acid solution that 10ml concentration is 2%, repeat said process twice at 25 DEG C after sonic oscillation 30min after centrifugalize cleaning.Obtaining faint yellow white powder after lyophilization is composite drug carried microsphere.The particle diameter adopting Zano ZS laser particle analyzer to test this microsphere is 5380nm, and adopting the absorbance of ultraviolet spectrophotometer testing drug, is 4.19% according to its encapsulation rate of formulae discovery.
Comparative example 3 (material beyond employing paraffin is as oil phase)
Taking 0.025g chitosan, to add 10ml concentration be in 1% acetic acid solution, be stirred to dissolving, add 0.025g taxol drug as aqueous phase, instilled in ethanol oil phase, ultrasonic emulsification 2min, adds 1ml glutaraldehyde under magnetic stirring, crosslinked end after 30min, 2500rpm centrifugalize, precipitate petroleum ether three final vacuum lyophilization 12h obtain chitosan drug-loading microsphere.Being added 10ml concentration is in the sodium sulfate glucosan acetic acid solution of 2%, adds the chitosan acetic acid solution that 10ml concentration is 2%, repeat said process twice at 25 DEG C after sonic oscillation 30min after centrifugalize cleaning.Obtaining faint yellow white powder after lyophilization is composite drug carried microsphere.The particle diameter adopting Zano ZS laser particle analyzer to test this microsphere is 2630nm, and adopting the absorbance of ultraviolet spectrophotometer testing drug, is 3.25% according to its encapsulation rate of formulae discovery.
Sustained release performance contrast test:
The chitosan microball 50mg got respectively in above-mentioned comparative example 1 and embodiment 8 adds in 100mlPBS buffer, and in water-bath constant temperature oscillator, 37 DEG C are carried out the contrast test of medicament slow release performance.Get 1ml sample test ultraviolet absorptivity after certain interval of time, the standard curve of drugs compared obtains concentration value.The buffer adding equal volume wherein is all needed after every sub-sampling.Concentration value and time are mapped and obtains elution profiles, as shown in Figure 2.Contrast that two curves can find out the release initial stage of product of the present invention prominent release phenomenon be improved significantly.
Table 1
Be mean diameter and the clad ratio of the paclitaxel microsphere that each embodiment and comparative example obtain in table 1, as can be seen from the data that table 1 provides, embodiment 1-8 is the chitosan taxol slow release microballoons that the present invention adopts self-assembling technique to prepare, its average particle size is Nano grade (289.5nm-675.7nm), and its minimum average particle diameters is 289.5nm.Comparative example 2 is the mean diameter of the microsphere not adopting the self-assembling technique of ultrasonic emulsification to prepare is 5380nm (5.38 μm), is nearly 20 times of the microspherulite diameter obtained in embodiment 3.Comparative example 3 is for have employed the self-assembly method of ultrasonic emulsification technology, but owing to have employed other oil phase (non-paraffin), therefore the particle diameter of its end product obtained is 2360nm (2.36 μm), the mean diameter of the microsphere obtained much larger than embodiment 1-8 equally.Therefore, when oil phase adopts paraffin, can dispersion effect be promoted, obtain product cut size and more easily control in uniform scope, and the microsphere of more small particle diameter can be obtained.
Comparative example 1 is the chitosan microball not adopting self-assembling technique to prepare, owing to which employs ultrasonic emulsification and paraffin as oil phase, therefore there is good mean diameter (430.5nm), but because it does not adopt self-assembling technique, therefore as can be seen from the curve of Fig. 2, the chitosan microball of comparative example 1 just reaches more than 80% at the preparation of first 10 hours, and the time that the sustained-release micro-spheres of embodiment of the present invention embodiment 8 takes more than 80% preparation to is more than 30 hours.
Nanoscale microsphere can obtained in conjunction with during ultrasonic emulsification technology as can be seen here when the specific oil phase of selection simultaneously.This is because when adopting paraffin as oil phase, because it disperses better in aqueous phase, and further increase its dispersion effect by ultrasonic emulsification, therefore reach Nano grade at the multilamellar microspherulite diameter prepared, and be evenly distributed (see Fig. 1).And efficiently solve the prominent of medicine by the multilayer coating structure of self assembly and release problem.
Beneficial effect
The shape of microsphere of the present invention is the circle of rule as can be seen from Figure 1, and its even particle size distribution, size is at about 600nm.And contrast visible with chitosan drug-loading microsphere as can be seen from Figure 2, composite drug carried microsphere shows as the feature of slow releasing, can avoid when making this finished product play curative effect like this in patient body initial prominently releasing the too high blood drug level brought, the certain valid density of maintenance that is released to for a long time subsequently provides guarantee, thus reaches the antitumous effect of long-acting slow-release.Therefore the microsphere supported particle diameter adopting self-assembling method of the present invention to prepare reaches Nano grade, it has higher drug loading, and add biological membrane crossing, release problem owing to which solving to dash forward simultaneously, extend release time, such medicine can play whole body therapeutic or diagnostic effect better, strengthens the curative effect of medicine at focus target site.Epithelial cell as diseased regions such as tumors is in a kind of leakage states, and due to nanoparticle long circulating in vivo, the chance that its medicine loaded enters the diseased regions such as tumor increases, and add the targeting to diseased region, macro-effect obviously improves curative effect.And because the present invention adopts self-assembling technique to make chitosan nano drug-carrying microsphere surface form multilayer film, and the release profiles of bound drug as required can design the composite drug carried microsphere of any number of plies, the present invention is owing to employing self-assembling technique, in conjunction with ultrasonic emulsification crosslinking technological, and have selected predetermined substance can obtain uniform nanometer particle size microsphere as oil phase, its narrow diameter distribution, drug loading is high, release time is long, compared with prior art there is better slow release effect, use the advantage of having more.
Above-mentionedly only several specific embodiments in the present invention to be illustrated; but can not as protection scope of the present invention; every according to the change of the equivalence done by design spirit in the present invention or to modify or equal proportion zooms in or out, all should think and fall into protection scope of the present invention.
Claims (4)
1. utilize self-assembling technique to prepare a method for taxol slow release microballoons, it is characterized in that comprising the following steps:
1) preparation of self assembly template:
Step 1: take 0.025g-0.01g chitosan, joins in the dilute acid soln of 10mL, is stirred to chitosan and dissolves completely, then adds 0.0025g-0.01g taxol drug as aqueous phase; Measure the liquid paraffin of 25mL-125mL as oil phase;
Step 2: aqueous phase is instilled in oil phase, then ultrasonic emulsification 1-2min, obtain finely dispersed water-in-oil emulsion, instill the glutaraldehyde solution of the concentration 37wt% of 1-2mL again, Keep agitation 30-40min, make its full cross-linked rear centrifugalize, precipitate petroleum ether three final vacuum lyophilizations 12 hours, obtain positively charged chitosan drug-loading microsphere; And it can be used as the template of following self assembling process;
2) self assembly taxol slow release microballoons preparation:
Step 3: above-mentioned positively charged chitosan drug-loading microsphere is placed in the polyanion sodium sulfate glucosan acetic acid solution that 10mL concentration is 2wt%, centrifugalize cleaning after sonic oscillation 30min at 25 DEG C; The electrostatic attraction effect self assembly between the polyelectolyte material of two kinds of oppositely chargeds is utilized to form the first tunic outside this template microsphere;
Step 4: obtain taxol slow release microballoons after again repeating above-mentioned steps 3 twice postlyophilization, the mean diameter of described microsphere is 200nm-700nm.
2. the method utilizing self-assembling technique to prepare taxol slow release microballoons according to claim 1, is characterized in that: described dilute acid soln is selected from acetic acid, formic acid or propanoic acid, and its concentration is 1wt%.
3. the method utilizing self-assembling technique to prepare taxol slow release microballoons according to claim 1, is characterized in that: described microsphere average grain diameter is 300nm-600nm.
4. a taxol slow release microballoons, it is characterized in that the taxol slow release microballoons prepared according to claim 1 or 2 or 3 either method.
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