CN110917171B - Protein nano microcapsule coated with poly sulfobetaine and preparation method thereof - Google Patents
Protein nano microcapsule coated with poly sulfobetaine and preparation method thereof Download PDFInfo
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- CN110917171B CN110917171B CN201811096951.8A CN201811096951A CN110917171B CN 110917171 B CN110917171 B CN 110917171B CN 201811096951 A CN201811096951 A CN 201811096951A CN 110917171 B CN110917171 B CN 110917171B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/38—Albumins
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5138—Organic macromolecular compounds; Dendrimers obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
Abstract
The invention provides a protein nano microcapsule coated with poly sulfobetaine and a preparation method thereof, wherein a protein solution and an N- (3-aminopropyl) methacrylate monomer are uniformly mixed, then the sulfobetaine monomer is added into the solution, a cross-linking agent is added under the stirring condition, the N- (3-aminopropyl) methacrylate monomer, the sulfobetaine monomer and the cross-linking agent are gathered around protein by utilizing electrostatic action and hydrogen bond action, then a catalyst and an initiator are added into the solution, and the protein nano microcapsule coated with poly sulfobetaine is finally prepared by an in-situ polymerization method. The invention utilizes the nano microcapsule to increase the stability of protein in blood, prolong the circulation time, reduce the toxicity of the protein and the medicament, have high-efficiency protein adsorption resistance, greatly improve the immunity of the protein and the medicament, reduce the toxic and side effect of functional protein on normal tissues and have better transfection capability.
Description
Technical Field
The invention relates to the technical field of biomedical materials, in particular to a protein nano microcapsule coated with poly sulfobetaine and a preparation method thereof.
Background
Glioblastoma is used as the tumor with the highest malignancy degree, the dispersity is extremely high, the traditional surgical removal is used as a common treatment mode, however, the risk is very high in the implementation of the surgical process, the complete removal cannot be carried out on some deep tumor parts, the survival rate is less than 10% after 5 years of surgery, the survival period does not exceed 15 months, and the treatment effect of glioblastoma is not satisfactory.
With the development of the field of biological molecules, the nano drug delivery technology brings a new development direction for the treatment of glioma. The nano drug delivery system mainly refers to a drug delivery system carrier from a few nanometers to hundreds of nanometers, and the nano particles provide a very promising platform for imaging and drug treatment and play an increasingly important role in diagnosis and treatment. However, the conventional nanoparticles have a fatal obstacle in clinical and medical applications, i.e., the nanoparticles easily adsorb proteins, cause opsonization, and are then phagocytosed and eliminated by macrophages, thereby greatly reducing the therapeutic effect of the drugs. Protein adsorption is the first stage of immune reaction, and considering how to modify the nanoparticles to increase the protein adsorption resistance of the nanoparticles so as to increase the pharmacological action of the drugs in vivo, the protein adsorption becomes a key step in the nano-drug delivery technology.
With the development of molecular biology, zwitterions become popular research hotspots, wherein sulfobetaine { [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide } serves as a zwitterion, and the charge balance effect and the hydration capability of the zwitterions make the sulfobetaine { [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide } a medical material with excellent protein adsorption resistance. Wei et al grafted a layer of sulfobetaine membrane on gold by an atom transfer radical polymerization method, incubated with human serum and plasma, and proved that the sulfobetaine membrane has good protein adsorption resistance; chen et al found that good protein adsorption resistance, anticoagulation and antithrombotic effects are achieved by grafting sulfobetaine on a polypropylene film by using a plasma induction method; zhai and the like synthesize a polycaprolactone-poly (diethylaminoethyl) methyl methacrylate-poly (sulfobetaine) triblock copolymer micelle by utilizing a click chemical reaction, and the polycaprolactone-poly (diethylaminoethyl) methyl methacrylate-poly (sulfobetaine) triblock copolymer micelle is used as a drug carrier of curcumin, and has a good slow release effect by utilizing the biocompatibility and the anti-protein adsorbability of sulfobetaine.
Disclosure of Invention
The invention overcomes the defects in the prior art, and provides a protein nano microcapsule encapsulated by poly-sulfobetaine and a preparation method thereof.
The purpose of the invention is realized by the following technical scheme.
The preparation method comprises the steps of uniformly mixing a protein solution and an N- (3-aminopropyl) methacrylate monomer, adding the sulfobetaine monomer into the solution, adding a cross-linking agent under the stirring condition, aggregating the N- (3-aminopropyl) methacrylate monomer, the sulfobetaine monomer and the cross-linking agent around protein by utilizing electrostatic action and hydrogen bond action, adding a catalyst and an initiator into the solution, and reacting for 0.1-48h at 4-40 ℃ by an in-situ polymerization method to finally prepare the protein nano microcapsule coated with the sulfobetaine; wherein the molar ratio of the protein to the N- (3-aminopropyl) methacrylate monomer to the sulfobetaine monomer is 1: (50-200): (3000-9000), the molar ratio of the protein to the cross-linking agent is 1: (50-4000), the molar ratio of the protein to the catalyst to the initiator is 1: (50-3000): (50-6000), the thickness of the poly-sulfobetaine shell layer is 1-10nm, and the diameter of the protein nano microcapsule coated by the poly-sulfobetaine is 7-30 nm.
The protein solution adopts one of nimotuzumab, cetuximab, PDL-1 monoclonal antibody and bovine serum albumin.
The molar ratio of the protein solution, the N- (3-aminopropyl) methacrylate monomer and the sulfobetaine monomer is 1: (100-200): (4000-8000).
The cross-linking agent is N, N' -methylene bisacrylamide, and the molar ratio of the protein solution to the cross-linking agent is 1: (100-3000).
The catalyst is N, N, N ', N' -tetramethyl ethylenediamine, the initiator is ammonium persulfate, and the molar ratio of the protein solution to the catalyst to the initiator is 1: (100-2000): (100-5000), and reacting for 2-24h at 4-40 ℃ by an in-situ polymerization method.
The thickness of the poly-sulfobetaine shell layer is 3-9nm, and the diameter of the protein nano microcapsule coated by the poly-sulfobetaine is 15-25 nm.
The invention has the beneficial effects that: the invention prepares the protein nano microcapsule encapsulated by the poly sulfobetaine, which has smooth surface, uniform particle size and protein adsorption resistance, by an in-situ free radical polymerization method. The invention utilizes the nano microcapsule to increase the stability of protein in blood, prolong the circulation time, reduce the toxicity of the protein and the medicament, have high-efficiency protein adsorption resistance, greatly improve the immunity of the protein and the medicament, reduce the toxic and side effect of functional protein on normal tissues and have better transfection capability. The preparation operation of the invention is carried out in water phase, which is efficient and convenient, safe and environment-friendly, and overcomes the problem of difficult heat dissipation in the traditional bulk polymerization. The invention has more than one protein, is easy to realize large-scale industrial production, and provides a wide application field for the development of biomedical materials.
Drawings
FIG. 1 is a transmission electron microscope image of a protein nanocapsule coated with polysulfonyl betaine prepared according to the present invention;
FIG. 2 is a particle size distribution diagram of the protein nanocapsule coated with the polysulfonyl betaine prepared by the present invention;
FIG. 3 is a gel electrophoresis image of a protein nanocapsule loaded with polysulfonylbetaine prepared in accordance with the present invention;
FIG. 4 is a protein adsorption drawing of a protein nanocapsule loaded with polysulfonylbetaine prepared in accordance with the present invention;
FIG. 5 is a transfection diagram of nanocapsules and macrophages of the polysulfonylbetaine-entrapped protein nanocapsules prepared in accordance with the present invention.
Detailed Description
The technical solution of the present invention is further illustrated by the following specific examples.
Example 1
Taking a solution containing 1mg of bovine serum albumin, adding monomer N- (3-aminopropyl) methacrylate, controlling the molar ratio of the bovine serum albumin to the N- (3-aminopropyl) methacrylate to be 1:50, and then adding sulfobetaine, wherein the molar ratio of the bovine serum albumin to the sulfobetaine is 1: 4000; then adding N, N' -methylene bisacrylamide according to the molar ratio of the bovine serum albumin to the cross-linking agent of 1:50, and enriching the monomers and the cross-linking agent around the bovine serum albumin by utilizing the electrostatic action and the hydrogen bond action under the action of continuous stirring; finally, with bovine serum albumin: catalyst: the initiator molar ratio is 1:100:400, and the catalyst N, N, N ', N' -tetramethyl ethylene diamine and the initiator ammonium persulfate are added. Reacting for 0.1h at 6 ℃ to prepare the protein nano microcapsule coated by the poly sulfobetaine.
Example 2
Taking a solution containing 1mg of nimotuzumab, adding a monomer N- (3-aminopropyl) methacrylate, controlling the molar ratio of nimotuzumab to N- (3-aminopropyl) methacrylate to be 1:100, and adding sulfobetaine, wherein the molar ratio of nimotuzumab to sulfobetaine is 1: 5000; then adding N, N' -methylene bisacrylamide according to the molar ratio of the nimotuzumab to the cross-linking agent of 1:100, and enriching the monomers and the cross-linking agent around the nimotuzumab by utilizing the electrostatic action and the hydrogen bond action under the action of continuous stirring; finally, the ratio of nimotuzumab: catalyst: the initiator molar ratio is 1:50:50, and the catalyst N, N, N ', N' -tetramethyl ethylene diamine and the initiator ammonium persulfate are added. And reacting for 48 hours at 4 ℃ to obtain the protein nano microcapsule coated by the poly sulfobetaine.
Example 3
Taking a solution containing 1mg of PDL-1, adding a monomer N- (3-aminopropyl) methacrylate, controlling the molar ratio of PDL-1 to N- (3-aminopropyl) methacrylate to be 1:150, and adding sulfobetaine, wherein the molar ratio of PDL-1 to sulfobetaine is 1: 3000; then adding N, N' -methylene bisacrylamide according to the molar ratio of PDL-1 to the cross-linking agent of 1:2000, and enriching the monomers and the cross-linking agent around PDL-1 by utilizing electrostatic action and hydrogen bond action under the action of continuous stirring; finally, the data is encoded in PDL-1: catalyst: the initiator molar ratio is 1:3000:6000, and the catalyst N, N, N ', N' -tetramethyl ethylenediamine and the initiator ammonium persulfate are added. Reacting for 2h at 40 ℃ to prepare the protein nano microcapsule coated by the poly sulfobetaine.
Example 4
Taking a solution containing 1mg of cetuximab, adding a monomer N- (3-aminopropyl) methacrylate, controlling the molar ratio of the cetuximab to the N- (3-aminopropyl) methacrylate to be 1:200, and then adding sulfobetaine, wherein the molar ratio of the cetuximab to the sulfobetaine is 1: 9000; then adding N, N' -methylene bisacrylamide according to the molar ratio of the cetuximab to the cross-linking agent of 1:4000, and enriching the monomers and the cross-linking agent around the cetuximab by utilizing the electrostatic action and the hydrogen bond action under the action of continuous stirring; finally, the mixture was mixed with cetuximab: catalyst: the initiator molar ratio is 1:2000:5000, and catalyst N, N, N ', N' -tetramethyl ethylene diamine and initiator ammonium persulfate are added. And reacting for 24 hours at 36 ℃ to obtain the protein nano microcapsule coated by the poly sulfobetaine.
Example 5
Taking a solution containing 1mg of bovine serum albumin, adding a monomer N- (3-aminopropyl) methacrylate, controlling the molar ratio of cetuximab to the N- (3-aminopropyl) methacrylate to be 1:120, and adding sulfobetaine, wherein the molar ratio of cetuximab to the sulfobetaine is 1: 3000; then adding N, N' -methylene bisacrylamide according to the molar ratio of the cetuximab to the cross-linking agent of 1:1000, and enriching the monomers and the cross-linking agent around the cetuximab by utilizing the electrostatic action and the hydrogen bond action under the action of continuous stirring; finally, the mixture was mixed with cetuximab: catalyst: the initiator molar ratio is 1:1000:4000, and the catalyst N, N, N ', N' -tetramethyl ethylene diamine and the initiator ammonium persulfate are added. Reacting for 36h at 30 ℃ to obtain the protein nano microcapsule coated by the poly sulfobetaine.
FIG. 1 is a transmission electron microscope image of the protein nanocapsule encapsulated by the poly sulfobetaine prepared by the invention, wherein the appearance of the protein nanocapsule is observed by adopting a transmission electron microscope produced by Japan electron optics company, a sample is dripped onto a copper mesh, and the nanocapsule is observed to be spherical after being dyed by tungsten phosphate, and the particle size of the nanocapsule is relatively uniform and is 15-25 nm.
FIG. 2 is a distribution diagram of the particle size of the protein nanocapsule encapsulated by the poly sulfobetaine prepared by the present invention, and the results of the test using a laser particle sizer/zeta-potentiostat manufactured by Brookhaven instruments of America show that the particle size of the nanocapsule is intensively distributed at about 20 nm.
FIG. 3 is a gel electrophoresis diagram of the protein nanocapsule coated with the poly sulfobetaine prepared by the invention, wherein agarose gel is prepared by adopting 1 XTAE buffer solution, the set voltage is 150V, the current is 40mA, and the test time is 10 minutes. The 365nm ultraviolet gel imaging system is used for collecting images, and the result shows that the unencapsulated protein band appears outside the hole, and the band of the prepared nano microcapsule appears in the hole. The results of particle size, gel permeation and transmission electron microscopy prove the successful preparation of the nanocapsule.
FIG. 4 is a protein absorption drawing of the protein nanocapsule coated with the poly sulfobetaine prepared by the present invention, and the ultraviolet spectrophotometer manufactured by soaring (Shanghai) instruments, Inc. is used for testing. After incubation with bovine serum albumin solutions with different concentrations, protein adsorption capacity is tested by the BCA kit, and the result shows that when the concentration of the bovine serum albumin is increased to 5mg/mL, the particle size is not obviously increased, which indicates that the protein adsorption resistance of the nano microcapsule is strong.
FIG. 5 shows the transfection pattern of the protein nanocapsules and macrophages encapsulated by the polysulfonyl betaines prepared in the present invention, which were tested by fluorescence confocal microscopy manufactured by Perking Elmer, USA. After co-incubation with macrophages, the endocytosis behavior of the cells to the nanocapsules is observed under a fluorescence microscope through DAPI staining, and the endocytosis behavior is found to be good.
The invention has been described in an illustrative manner, and it is to be understood that any simple variations, modifications or other equivalent changes which can be made by one skilled in the art without departing from the spirit of the invention fall within the scope of the invention.
Claims (8)
1. The protein nano microcapsule coated by the poly sulfobetaine is characterized in that: uniformly mixing a protein solution and an N- (3-aminopropyl) methacrylate monomer, adding a sulfobetaine monomer into the solution, adding a cross-linking agent under the condition of stirring, aggregating the N- (3-aminopropyl) methacrylate monomer, the sulfobetaine monomer and the cross-linking agent around the protein by utilizing the electrostatic action and the hydrogen bond action, adding a catalyst and an initiator into the solution, and reacting for 0.1-48h at 4-40 ℃ by an in-situ polymerization method to finally prepare the protein nano microcapsule coated by the sulfobetaine; wherein the molar ratio of the protein to the N- (3-aminopropyl) methacrylate monomer to the sulfobetaine monomer is 1: (50-200): (3000-9000), the molar ratio of the protein to the cross-linking agent is 1: (50-4000), the molar ratio of the protein to the catalyst to the initiator is 1: (50-3000): (50-6000), the thickness of the poly-sulfobetaine shell layer is 1-10nm, the diameter of the poly-sulfobetaine-coated protein nano microcapsule is 7-30nm, the protein solution adopts one of nimotuzumab, cetuximab, PDL-1 monoclonal antibody and bovine serum albumin, the catalyst is N, N, N ', N' -tetramethyl ethylenediamine, and the initiator is ammonium persulfate.
2. The polysulfonobetaine-entrapped protein nanocapsule of claim 1 wherein: the molar ratio of the protein solution, the N- (3-aminopropyl) methacrylate monomer and the sulfobetaine monomer is 1: (100-200): (4000-8000).
3. The polysulfonobetaine-entrapped protein nanocapsule of claim 1 wherein: the cross-linking agent is N, N' -methylene bisacrylamide, and the molar ratio of the protein solution to the cross-linking agent is 1: (100-3000).
4. The polysulfonobetaine-entrapped protein nanocapsule of claim 1 wherein: the molar ratio of the protein solution to the catalyst to the initiator is 1: (100-2000): (100-5000), reacting for 2-24h by an in-situ polymerization method at 4-40 ℃ to obtain the protein nanocapsule coated with the poly sulfobetaine, wherein the thickness of the poly sulfobetaine shell layer is 3-9nm, and the diameter of the protein nanocapsule coated with the poly sulfobetaine is 15-25 nm.
5. The method for preparing the polysulfonylbetaine-coated protein nanocapsule as claimed in any one of claims 1 to 4, wherein: uniformly mixing a protein solution and an N- (3-aminopropyl) methacrylate monomer, adding a sulfobetaine monomer into the solution, adding a cross-linking agent under the condition of stirring, aggregating the N- (3-aminopropyl) methacrylate monomer, the sulfobetaine monomer and the cross-linking agent around the protein by utilizing the electrostatic action and the hydrogen bond action, adding a catalyst and an initiator into the solution, and reacting for 0.1-48h at 4-40 ℃ by an in-situ polymerization method to finally prepare the protein nano microcapsule coated by the sulfobetaine; wherein the molar ratio of the protein to the N- (3-aminopropyl) methacrylate monomer to the sulfobetaine monomer is 1: (50-200): (3000-9000), the molar ratio of the protein to the cross-linking agent is 1: (50-4000), the molar ratio of the protein to the catalyst to the initiator is 1: (50-3000): (50-6000), the thickness of the poly-sulfobetaine shell layer is 1-10nm, the diameter of the poly-sulfobetaine-coated protein nano microcapsule is 7-30nm, the protein solution adopts one of nimotuzumab, cetuximab, PDL-1 monoclonal antibody and bovine serum albumin, the catalyst is N, N, N ', N' -tetramethyl ethylenediamine, and the initiator is ammonium persulfate.
6. The method for preparing the polysulfonylbetaine-coated protein nanocapsule of claim 5 wherein: the molar ratio of the protein solution, the N- (3-aminopropyl) methacrylate monomer and the sulfobetaine monomer is 1: (100-200): (4000-8000).
7. The method for preparing the polysulfonylbetaine-coated protein nanocapsule of claim 5 wherein: the cross-linking agent is N, N' -methylene bisacrylamide, and the molar ratio of the protein solution to the cross-linking agent is 1: (100-3000).
8. The method for preparing the polysulfonylbetaine-coated protein nanocapsule of claim 5 wherein: the molar ratio of the protein solution to the catalyst to the initiator is 1: (100-2000): (100-5000), reacting for 2-24h by an in-situ polymerization method at 4-40 ℃ to obtain the protein nanocapsule coated with the poly sulfobetaine, wherein the thickness of the poly sulfobetaine shell layer is 3-9nm, and the diameter of the protein nanocapsule coated with the poly sulfobetaine is 15-25 nm.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014210546A1 (en) * | 2013-06-27 | 2014-12-31 | University Of Washington Through Its Center For Commercialization | Biocompatible polymeric system for targeted treatment of thrombotic and hemostatic disorders |
| CN105663084A (en) * | 2016-03-03 | 2016-06-15 | 天津医科大学总医院 | Poly(2-methacryloyloxyethyl phosphorylcholine) entrapped nimotuzumab nanocapsule, as well as preparation method and application thereof |
| CN107126936A (en) * | 2017-04-17 | 2017-09-05 | 天津大学 | A kind of blood-purifying adsorbing agent and preparation method with embedded material |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014210546A1 (en) * | 2013-06-27 | 2014-12-31 | University Of Washington Through Its Center For Commercialization | Biocompatible polymeric system for targeted treatment of thrombotic and hemostatic disorders |
| CN105663084A (en) * | 2016-03-03 | 2016-06-15 | 天津医科大学总医院 | Poly(2-methacryloyloxyethyl phosphorylcholine) entrapped nimotuzumab nanocapsule, as well as preparation method and application thereof |
| CN107126936A (en) * | 2017-04-17 | 2017-09-05 | 天津大学 | A kind of blood-purifying adsorbing agent and preparation method with embedded material |
Non-Patent Citations (2)
| Title |
|---|
| "Polysulfobetaine-based diblock copolymer nanoobjects via polymerization-induced self-assembly";Kay E. B. Doncom et al.;《Polymer Chemistry》;20151231;第6卷;第7264–7273页 * |
| "多巴胺端基聚磺基甜菜碱的表面改性及其表面抗蛋白吸附性能";龚伟等;《华东理工大学学报（自然科学版）》;20180630;第44卷(第3期);第316-322页 * |
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