CN103948914A - Method for preparing drug-loadable low-molecular-weight water-soluble chitosan nano-particle - Google Patents
Method for preparing drug-loadable low-molecular-weight water-soluble chitosan nano-particle Download PDFInfo
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Abstract
The invention provides a method for preparing a drug-loadable low-molecular-weight water-soluble chitosan nano-particle. The method comprises the following steps: a, dissolving water-soluble chitosan in deionized water to prepare a water-soluble chitosan solution with concentration of 2-10mg/ml; b, sequentially adding a bovine serum albumin aqueous solution with concentration of 0.1-0.3mg/ml and sodium tripolyphosphate aqueous solution with concentration of 0.1-0.3mg/ml, and spontaneously generating a drug-loaded nano-particle under room-temperature stirring condition, wherein the volume ratio of the water-soluble chitosan solution to bovine serum albumin aqueous solution to sodium tripolyphosphate aqueous solution is 1:(0.1-0.3):(0.1-0.3). According to the method, the water-soluble chitosan nano-particle can be obtained under a neutral condition and plays a role in sustainably releasing bovine serum albumin and other medicaments, the process is simple and practical, and the nano-particle is small in average grain diameter.
Description
Technical field
The present invention relates to a kind of preparation method of low molecular weight water-soluble shitosan nanoparticle of medicine-carried.
Background technology
Chitosan is the unique natural alkaline polysaccharide of occurring in nature, its ultimate unit is glucamine, water insoluble, alkaline solution or ordinary organic solvents, but dissolve in hydrochloric acid, nitric acid, formic acid, the diluted acids such as acetic acid, chitosan is with its good characteristic, the biological example compatibility, degradability, avirulence, adsorptivity, source is abundant etc., at medicine, food, chemical industry, agricultural, be used widely in the fields such as environmental protection, and in quilt Japan in 1991, the U.S., medical circle and the nutraceutical research institution on the ground such as Europe regard as at carbohydrate, protein, fat, vitamin, the sixth-largest vital principle after mineral.
Chitosan has biocompatibility, avirulence and bioadhesive, can make medicine keep high concentration in part, and can open cutaneomucosal tight connection, strengthens the osmosis of medicine at mucosa.Chitin nanometer has more superioritys than micron particle, can make macromole smoothly by epithelial tissue, promotes the osmotic absorption of medicine, and suitable finishing makes it have targeting to certain organs or focus.Be particularly useful for the more convenient route of administration such as oral or mucosa, can prolong drug circulation time in vivo, effectively improve the bioavailability of medicine, reduce side effect.
Because conventional chitosan molecule amount is large, viscosity is high, cannot under physiological pH condition, dissolve, limit the application of chitosan as vaccine carrier.And the cytotoxicity of low-molecular-weight chitosan and nanoparticle thereof is lower, nanoparticle can significantly increase the picked-up effect of A549 cell.
At present prepare in nanoparticle process must be using acetic acid as solubilizing agent, and acetic acid environment has produced serious impact to biologically active drug.These shortcomings are main relevant with the physico-chemical property such as N-degree of acetylation, molecular weight of chitosan.
Summary of the invention
The object of this invention is to provide the preparation method of the low molecular weight water-soluble shitosan nanoparticle of the medicine-carried that the nanoparticle mean diameter of a kind of technique simple possible, gained is little,
The preparation method of the low molecular weight water-soluble shitosan nanoparticle of a kind of medicine-carried provided by the invention, the method comprises the steps:
A, water-soluble chitosan is dissolved in to the water-soluble chitosan solution of configuration concentration 2-10mg/ml in deionized water;
B, add successively the bovine serum albumin aqueous solution of concentration 0.1-0.3mg/ml and the tripolyphosphate sodium water solution of concentration 0.1-0.3mg/ml, under stirring at room temperature condition, spontaneous generation medicine-carried nano particles;
Wherein, the volume ratio of water-soluble chitosan solution, bovine serum albumin aqueous solution and tripolyphosphate sodium water solution is 1:(0.1-0.3): (0.1-0.3).
In above-mentioned, the concentration of bovine serum albumin aqueous solution is preferably 0.2mg/ml, and the concentration of tripolyphosphate sodium water solution is preferably 0.2mg/ml.The volume ratio of water-soluble chitosan solution, bovine serum albumin aqueous solution and tripolyphosphate sodium water solution is preferably 1:0.2:0.2.
The beneficial effect that the present invention has: obtain water-soluble chitosan nano particle under neutrallty condition, be there is to slow release effect in the medicines such as bovine serum albumin, therefore, this chitosan particle is expected to become the slow-released carrier of some medicines, in medical research for the preparation of sustained release pharmaceutical formulation.
Detailed description of the invention
In following embodiment, the molecular weight of water-soluble chitosan is that 6.3 kDa, deacetylation are 90.7%; The molecular weight of the bovine serum albumin of preparation bovine serum albumin aqueous solution is 68kDa.
Embodiment 1
Water-soluble chitosan is dissolved in to the water-soluble chitosan solution of the 2mg/ml that is made into 5 ml in deionized water.Under room temperature and magnetic agitation condition, add successively the bovine serum albumin aqueous solution 1ml of concentration 0.2mg/ml and the tripolyphosphate sodium water solution 1ml of concentration 0.2mg/ml, under stirring at room temperature condition, spontaneous generation medicine-carried nano particles.The mean diameter of the medicine-carried nano particles of gained is 135.5 ± 10.2 nm.
Embodiment 2
Water-soluble chitosan is dissolved in to the water-soluble chitosan solution of the 2.8mg/ml that is made into 5 ml in deionized water.Under room temperature and magnetic agitation condition, add successively the bovine serum albumin aqueous solution 1ml of concentration 0.2mg/ml and the tripolyphosphate sodium water solution 1ml of concentration 0.2mg/ml, under stirring at room temperature condition, spontaneous generation medicine-carried nano particles.The mean diameter of the medicine-carried nano particles of gained is 99.7 ± 9.4 nm.
Embodiment 3
Water-soluble chitosan is dissolved in to the water-soluble chitosan solution of the 3.6mg/ml that is made into 5 ml in deionized water.Under room temperature and magnetic agitation condition, add successively the bovine serum albumin aqueous solution 1ml of concentration 0.2mg/ml and the tripolyphosphate sodium water solution 1ml of concentration 0.2mg/ml, under stirring at room temperature condition, spontaneous generation medicine-carried nano particles.The mean diameter of the medicine-carried nano particles of gained is 110.2 ± 11.3 nm.
Embodiment 4
Water-soluble chitosan is dissolved in to the water-soluble chitosan solution of the 4mg/ml that is made into 5 ml in deionized water.Under room temperature and magnetic agitation condition, add successively the bovine serum albumin aqueous solution 1ml of concentration 0.2mg/ml and the tripolyphosphate sodium water solution 1ml of concentration 0.2mg/ml, under stirring at room temperature condition, spontaneous generation medicine-carried nano particles.The mean diameter of the medicine-carried nano particles of gained is 55.1 ± 8.7 nm.
Embodiment 5
Water-soluble chitosan is dissolved in to the water-soluble chitosan solution of the 6mg/ml that is made into 5 ml in deionized water.Under room temperature and magnetic agitation condition, add successively the bovine serum albumin aqueous solution 1ml of concentration 0.2mg/ml and the tripolyphosphate sodium water solution 1ml of concentration 0.2mg/ml, under stirring at room temperature condition, spontaneous generation medicine-carried nano particles.The mean diameter of the medicine-carried nano particles of gained is 127.3 ± 10.7nm.
Embodiment 6
Water-soluble chitosan is dissolved in to the water-soluble chitosan solution of the 7mg/ml that is made into 5 ml in deionized water.Under room temperature and magnetic agitation condition, add successively the bovine serum albumin aqueous solution 1ml of concentration 0.2mg/ml and the tripolyphosphate sodium water solution 1ml of concentration 0.2mg/ml, under stirring at room temperature condition, spontaneous generation medicine-carried nano particles.The mean diameter of the medicine-carried nano particles of gained is 124.7 ± 9.9nm.
Embodiment 7
Water-soluble chitosan is dissolved in to the water-soluble chitosan solution of the 8mg/ml that is made into 5 ml in deionized water.Under room temperature and magnetic agitation condition, add successively the bovine serum albumin aqueous solution 1ml of concentration 0.2mg/ml and the tripolyphosphate sodium water solution 1ml of concentration 0.2mg/ml, under stirring at room temperature condition, spontaneous generation medicine-carried nano particles.The mean diameter of the medicine-carried nano particles of gained is 111.7 ± 8.7nm.
Embodiment 8
Water-soluble chitosan is dissolved in to the water-soluble chitosan solution of the 10mg/ml that is made into 5 ml in deionized water.Under room temperature and magnetic agitation condition, add successively the bovine serum albumin aqueous solution 1ml of concentration 0.2mg/ml and the tripolyphosphate sodium water solution 1ml of concentration 0.2mg/ml, under stirring at room temperature condition, spontaneous generation medicine-carried nano particles.The mean diameter of the medicine-carried nano particles of gained is 135.5 ± 10.2nm.
Claims (4)
1. a preparation method for the low molecular weight water-soluble shitosan nanoparticle of medicine-carried, is characterized in that, the method comprises the steps:
A, water-soluble chitosan is dissolved in to the water-soluble chitosan solution of configuration concentration 2-10mg/ml in deionized water;
B, add successively the bovine serum albumin aqueous solution of concentration 0.1-0.3mg/ml and the tripolyphosphate sodium water solution of concentration 0.1-0.3mg/ml, under stirring at room temperature condition, spontaneous generation medicine-carried nano particles;
Wherein, wherein, the volume ratio of water-soluble chitosan solution, bovine serum albumin aqueous solution and tripolyphosphate sodium water solution is 1:(0.1-0.3): (0.1-0.3).
2. the preparation method of the low molecular weight water-soluble shitosan nanoparticle of a kind of medicine-carried according to claim 1, is characterized in that, the concentration of bovine serum albumin aqueous solution is 0.2mg/ml.
3. the preparation method of the low molecular weight water-soluble shitosan nanoparticle of a kind of medicine-carried according to claim 1, is characterized in that, the concentration of tripolyphosphate sodium water solution is 0.2mg/ml.
4. the preparation method of the low molecular weight water-soluble shitosan nanoparticle of a kind of medicine-carried according to claim 1, is characterized in that, the volume ratio of water-soluble chitosan solution, bovine serum albumin aqueous solution and tripolyphosphate sodium water solution is 1:0.2:0.2.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104906073A (en) * | 2015-06-10 | 2015-09-16 | 青岛大学附属医院 | Preparation method of chitosan quaternary ammonium salt hyaluronic acid nanogel coated with basic fibroblast growth factors |
| CN104958251A (en) * | 2015-06-10 | 2015-10-07 | 杨甫进 | Preparation method of hyaluronic acid nanogel |
| CN111420067A (en) * | 2020-03-09 | 2020-07-17 | 西南交通大学 | Composite microsphere nano-carrier and preparation method and application thereof |
| CN112245392A (en) * | 2020-10-25 | 2021-01-22 | 台州职业技术学院 | Preparation and application of low-molecular-weight chitosan modified fatty acid drug-loaded vesicle |
Citations (1)
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|---|---|---|---|---|
| CN1686560A (en) * | 2005-04-08 | 2005-10-26 | 武汉大学 | Chitin tetra ammonium salt nano-particle, its preparation method and use |
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2014
- 2014-05-14 CN CN201410200562.0A patent/CN103948914A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1686560A (en) * | 2005-04-08 | 2005-10-26 | 武汉大学 | Chitin tetra ammonium salt nano-particle, its preparation method and use |
Non-Patent Citations (4)
| Title |
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| 王春: "Release Model of Water-soluble chitosan nanoparticles forprotein delivery", 《AGIOULTURAL SCIENCE&TECHNOLOGY》 * |
| 王春: "水溶性壳聚糖载体的制备及其蛋白药物负载性能的研究", 《华南理工大学博士学位论文》 * |
| 王春等: "Water-soluble+chitosan+nanoparticles+as+a+novel+carrier+system+for+protein+delivery", 《CHINESE SCIENCE EULLETIN》 * |
| 王春等: "水溶性壳聚糖纳米载体蛋白药物的体外释放模型", 《安徽农业科学》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104906073A (en) * | 2015-06-10 | 2015-09-16 | 青岛大学附属医院 | Preparation method of chitosan quaternary ammonium salt hyaluronic acid nanogel coated with basic fibroblast growth factors |
| CN104958251A (en) * | 2015-06-10 | 2015-10-07 | 杨甫进 | Preparation method of hyaluronic acid nanogel |
| CN104958251B (en) * | 2015-06-10 | 2018-05-29 | 青岛市中心医院 | A kind of preparation method of hyaluronic acid nanometer gel |
| CN104906073B (en) * | 2015-06-10 | 2018-08-10 | 青岛大学附属医院 | A kind of preparation method for the chitosan quaternary ammonium salt hyaluronic acid nanometer gel containing basic fibroblast growth factor |
| CN111420067A (en) * | 2020-03-09 | 2020-07-17 | 西南交通大学 | Composite microsphere nano-carrier and preparation method and application thereof |
| CN112245392A (en) * | 2020-10-25 | 2021-01-22 | 台州职业技术学院 | Preparation and application of low-molecular-weight chitosan modified fatty acid drug-loaded vesicle |
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