CN110448734A - The preparation method of composite drug-loaded delivery materials based on hydrogel and liposome - Google Patents
The preparation method of composite drug-loaded delivery materials based on hydrogel and liposome Download PDFInfo
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- CN110448734A CN110448734A CN201910828528.0A CN201910828528A CN110448734A CN 110448734 A CN110448734 A CN 110448734A CN 201910828528 A CN201910828528 A CN 201910828528A CN 110448734 A CN110448734 A CN 110448734A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/20—Polysaccharides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/52—Hydrogels or hydrocolloids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/06—Materials or treatment for tissue regeneration for cartilage reconstruction, e.g. meniscus
Abstract
The preparation method of composite drug-loaded delivery materials based on hydrogel and liposome, the invention belongs to technical field of biological materials, it discharges fast technical problem to solve to carry medicine as cartilage defect repair timbering material hydrogel.Lipoid and drug: one, being dissolved in organic solvent by preparation method in a reservoir, and after completely dissolution, rotary evaporation removes organic solvent, liposome membrane is formed in vessel surface, buffer solution is added, sufficiently oscillation makes liposome membrane aquation fall off, and obtains liposome solutions；Two, liposome solutions and polyglycol solution are sufficiently mixed, the derivative solution of chitosan solution or chitosan is added, obtains the composite drug-loaded delivery materials based on hydrogel and liposome after standing.Invented liposomes can carrying medicament, realize long-acting slow release, can be used as the vehicle delivery system of drug；The two synergistic effect, can be realized the long-acting slow release of timbering material carrying medicament.
Description
Technical field
The invention belongs to technical field of biological materials, and in particular to a kind of preparation method of composite drug-loaded delivery materials.
Background technique
Articular cartilage damage rate in China's is up to 10%-17%, the 60%-70% of Zhan Suoyou joint disease at present.However, soft
The transfer ability of osteocyte is very limited, and does not have blood supply, and therefore, the self-repairing capability of articular cartilage is very limited.Joint
Cartilage is difficult to regenerate once damaging, if treating not in time, 75% can develop into Osteoarthritis (OA), the later period of osteoarthritis
Need to receive joint replacement surgery, it is expensive, and great pain can be brought to patient, quality of the life decline.
Cartilage tissue engineered rise provides new developing direction for the reparation of articular cartilage.Cartilage tissue engineered three
Big fundamental is: timbering material, seed cell and active factors.Since the proliferative capacity of cartilage cell itself has very much
Limit, studying more seed cell at present is mainly that (joint fluid mescenchymal stem cell, umbilical cord mesenchyma are dry thin for mescenchymal stem cell
Born of the same parents, mesenchymal stem cell etc.).Timbering material can provide the microenvironment of existence for cell, be cell growth, proliferation, divide
Change and migrate the place of depended on carrier and nutriment exchange and metabolism.Because timbering material is in cartilaginous tissue
Play the role of bridge and tie in engineering.Contain a large amount of moisture in hydrogel, due to its softness, three dimensional network can be formed
Network structure is conducive to the conveying of nutriment and the output of metabolite, and has good biocompatibility, is organizational project
Ideal material.But hydrogel, as cartilage tissue scaffold material, porosity is big, when carrying medicament or growth factor retain
Between it is short；And the reparation of cartilage defect is a long-term process.Therefore, effectively extend hydrogel carrying medicament or growth because
The release time of son is most important.
Liposome have class cell as a result, hydrophilic phospholipid head reaches in water, hydrophobic tail portion is towards air, after agitation
The spherical liposomes of phospholipid bilayer can be formed, hydrophobic drug is wrapped in liposome interior or by hydrophilic medicament packet
It is wrapped in hydrophilic radical interlayer.The stock size of liposome is that 25-1000nm is differed.Since preparing for liposome is simple, cell parent
The advantages that, targeting low with property, histocompatbility, cellular affinity, toxic side effect and slow release, it is wide to carry medicine for liposome at present
It is concerned.
Summary of the invention
The purpose of the present invention is to solve carry medicine as cartilage defect repair timbering material hydrogel to discharge fast technology
Problem, and the preparation method of a kind of hydrogel and liposome compound support frame material is provided.
The present invention is based on the preparation methods of hydrogel and the composite drug-loaded delivery materials of liposome to follow these steps to realize:
One, lipoid and drug: being dissolved in organic solvent by the preparation of liposome in a reservoir, after completely dissolution, rotation
Evaporating organic solvent forms liposome membrane in vessel surface, and buffer solution is added, and sufficiently oscillation keeps liposome membrane aquation de-
It falls, obtains liposome solutions；
Two, the preparation of composite drug-loaded delivery materials: the liposome solutions and polyglycol solution that step 1 is obtained are abundant
Mixing, it is to be mixed uniformly after, the derivative solution of chitosan solution or chitosan is added, is obtained after standing based on hydrogel and rouge
The composite drug-loaded delivery materials of plastid.
In the compound system of hydrogel and liposome that the present invention is prepared, the compatibility of hydrogel is good, can be used as group
The timbering material of weaver's journey；Meanwhile liposome can carrying medicament, realize long-acting slow release, can be used as the vehicle delivery of drug
System；The two synergistic effect, can be realized the long-acting slow release of timbering material carrying medicament.
The composite drug-loaded delivery materials based on hydrogel and liposome that the present invention is prepared can be widely applied to tissue
Engineering field.
Detailed description of the invention
Fig. 1 is the liposomal particle size figure that 1 step 1 of embodiment obtains；
Fig. 2 is the drug release patterns figure of the composite drug-loaded delivery materials based on hydrogel and liposome, and wherein ■ is represented
Composite drug-loaded delivery materials based on hydrogel and liposome, ● liposome is represented, ▲ represent hydrogel.
Specific embodiment
Specific embodiment 1: the preparation side of composite drug-loaded delivery materials of the present embodiment based on hydrogel and liposome
Method follows these steps to implement:
One, lipoid and drug: being dissolved in organic solvent by the preparation of liposome in a reservoir, after completely dissolution, rotation
Evaporating organic solvent forms liposome membrane in vessel surface, and buffer solution is added, and sufficiently oscillation keeps liposome membrane aquation de-
It falls, obtains liposome solutions；
Two, the preparation of composite drug-loaded delivery materials: the liposome solutions and polyglycol solution that step 1 is obtained are abundant
Mixing, it is to be mixed uniformly after, the derivative solution of chitosan solution or chitosan is added, is obtained after standing based on hydrogel and rouge
The composite drug-loaded delivery materials of plastid.
Chitosan solution and polyglycol solution obtain hydrogel after sufficiently dissolving mixing in present embodiment step 2.Shell
The solvent of the derivative solution of glycan solution or chitosan is water or buffer.
The solution that water-soluble substances are added in present embodiment step 1 lipid membrane forms liposome；Then liposome is molten
Liquid and chitosan solution after mixing, add polyglycol solution, form the compound system of hydrogel and liposome.The system
The compound system that Preparation Method obtains, hydrogel compatibility is good, can be used as the timbering material of organizational project；Meanwhile liposome can be born
Drug is carried, long-acting slow release is realized, can be used as the vehicle delivery system of drug；The two acts synergistically, it can be achieved that timbering material
The long-acting slow release of carrying medicament
Specific embodiment 2: the present embodiment is different from the first embodiment in that lipoid described in step 1 is phosphorus
Rouge or cholesterol.
Specific embodiment 3: the present embodiment is different from the first and the second embodiment in that medicine described in step 1
Object is the drug of cartilage defect repair or the factor for promoting cartilage differentiation.
Drug described in present embodiment can be chondroitin sulfate, kartogenin (KGN) etc..
Specific embodiment 4: unlike one of present embodiment and specific embodiment one to three described in step 1
Organic solvent be ethyl alcohol, methylene chloride or dimethyl sulfoxide.
Specific embodiment 5: unlike one of present embodiment and specific embodiment one to four described in step 1
Buffer be deionized water, phosphate buffer or Tris-HCl buffer.
Specific embodiment 6: unlike one of present embodiment and specific embodiment one to five described in step 2
Chitosan derivative be hydroxyethyl chitosan or carboxyetbyl chitosan.
Specific embodiment 7: unlike one of present embodiment and specific embodiment one to six described in step 2
Polyethylene glycol be polyethylene glycol that aldehyde radical is end group.
Specific embodiment 8: unlike one of present embodiment and specific embodiment one to seven described in step 2
The molecular weight ranges of chitosan be 1000~100k Da, the molecular weight ranges of polyethylene glycol are 500~1000k Da.
Specific embodiment 9: institute's shape in step 2 unlike one of present embodiment and specific embodiment one to eight
At composite drug-loaded delivery materials, final concentration 10~100mg/mL of range of chitosan solution, the final concentration of polyglycol solution
Range is 10~500mg/mL, and the concentration range of liposome is 1~20wt%.
Specific embodiment 10: unlike one of present embodiment and specific embodiment one to nine described in step 2
Time of repose be 0.5~5min.
Embodiment 1: the preparation method of composite drug-loaded delivery materials of the present embodiment based on hydrogel and liposome is by following
Step is implemented:
One, the preparation of liposome: 1g phosphatide (molecular weight 600Da) and 10mg kartogenin are dissolved in a reservoir
In methylene chloride, after completely dissolution, rotary evaporation removes methylene chloride, forms liposome membrane in vessel surface, 10mL is added
The phosphate buffer that pH is 7.4, sufficiently oscillation make liposome membrane aquation fall off, and obtain liposome solutions；
Two, the preparation of composite drug-loaded delivery materials: liposome solutions and end group that step 1 is obtained are the poly- second of aldehyde radical
Glycol solution (molecular weight: 2kDa) is sufficiently mixed, it is to be mixed uniformly after, be added hydroxyethyl chitosan solution (molecular weight:
80kDa), 1min is stood, the hydrogel containing liposome, the as composite drug-loaded delivering material based on hydrogel and liposome are obtained
Material.
The mass concentration of liposome is 5% in the composite drug-loaded delivery materials that the present embodiment obtains, and Polyethylene glycol is
15mg/ml；The concentration of chitosan is 25mg/ml.
The partial size for the liposome that the present embodiment step 1 obtains is as shown in attached drawing 1.
The drug release patterns of composite drug-loaded delivery materials of the present embodiment based on hydrogel and liposome are shown in attached drawing 2.From
As can be seen that in the case where identical drugloading rate in attached drawing 2, when release was to 1 day, the burst size of carrying medicament is in hydrogel
94.8%, and the burst size of composite drug-loaded delivery system carrying medicament is 12.7%, therefore, composite drug-loaded delivery system has good
Good slow releasing function.
Embodiment 2: the preparation method of composite drug-loaded delivery materials of the present embodiment based on hydrogel and liposome is by following
Step is implemented:
One, 1.5g cholesterol and 50mg chondroitin sulfate: being dissolved in methylene chloride by the preparation of liposome in a reservoir,
After completely dissolution, rotary evaporation removes methylene chloride, forms liposome membrane in vessel surface, the phosphoric acid that 10mL pH is 7.4 is added
Salt buffer, sufficiently oscillation make liposome membrane aquation fall off, and obtain liposome solutions；
Two, the preparation of composite drug-loaded delivery materials: liposome solutions and end group that step 1 is obtained are the poly- second of aldehyde radical
Glycol solution (molecular weight: 1kDa, concentration 100mg/mL) is sufficiently mixed, it is to be mixed uniformly after, be added hydroxyethyl chitosan it is molten
Liquid (molecular weight: 80kDa, concentration 50mg/mL) stands 0.5min, obtains the hydrogel containing liposome, is as based on hydrogel
With the composite drug-loaded delivery materials of liposome.
When release was to 1 day, the burst size of carrying medicament is 86.5% in the hydrogel, and the composite drug-loaded delivery system is negative
The burst size for carrying drug is 9.7%.
Embodiment 3: the preparation method of composite drug-loaded delivery materials of the present embodiment based on hydrogel and liposome is by following
Step is implemented:
One, the preparation of liposome: in a reservoir that phosphatide (molecular weight 1000Da, 1.2g) and 5mg kartogenin is molten
Solution is in dehydrated alcohol, and after completely dissolution, rotary evaporation removes methylene chloride, forms liposome membrane in vessel surface, is added
Trishydroxymethylaminomethane (Tris) buffer that 10mL pH is 7.4, sufficiently oscillation make liposome membrane aquation fall off, and obtain rouge
Plastid solution；
Two, the preparation of composite drug-loaded delivery materials: liposome solutions and end group that step 1 is obtained are the poly- second of aldehyde radical
Glycol solution (molecular weight: 10kDa, concentration 50mg/mL) is sufficiently mixed, it is to be mixed uniformly after, be added hydroxyethyl chitosan it is molten
Liquid (molecular weight: 200kDa, concentration 20mg/mL) stands 5min, obtains the hydrogel containing liposome, is as based on hydrogel
With the composite drug-loaded delivery materials of liposome.
When release was to 1 day, the burst size of carrying medicament is 97.1% in the hydrogel, and the composite drug-loaded delivery system is negative
The burst size for carrying drug is 19.7%.
Claims (10)
1. the preparation method of the composite drug-loaded delivery materials based on hydrogel and liposome, it is characterised in that the preparation method is pressed
Column step is realized:
One, lipoid and drug: being dissolved in organic solvent by the preparation of liposome in a reservoir, after completely dissolution, rotary evaporation
Organic solvent is removed, liposome membrane is formed in vessel surface, buffer solution is added, sufficiently oscillation makes liposome membrane aquation fall off,
Obtain liposome solutions；
Two, the preparation of composite drug-loaded delivery materials: liposome solutions and polyglycol solution that step 1 obtains are sufficiently mixed,
It is to be mixed uniformly after, the derivative solution of chitosan solution or chitosan is added, is obtained after standing based on hydrogel and liposome
Composite drug-loaded delivery materials.
2. the preparation method of the composite drug-loaded delivery materials according to claim 1 based on hydrogel and liposome, special
Sign is that lipoid described in step 1 is phosphatide or cholesterol.
3. the preparation method of the composite drug-loaded delivery materials according to claim 1 based on hydrogel and liposome, special
Sign is the drug or the factor for promoting cartilage differentiation that drug described in step 1 is cartilage defect repair.
4. the preparation method of the composite drug-loaded delivery materials according to claim 1 based on hydrogel and liposome, special
Sign is that organic solvent described in step 1 is ethyl alcohol, methylene chloride or dimethyl sulfoxide.
5. the preparation method of the composite drug-loaded delivery materials according to claim 1 based on hydrogel and liposome, special
Sign is that buffer described in step 1 is deionized water, phosphate buffer or Tris-HCl buffer.
6. the preparation method of the composite drug-loaded delivery materials according to claim 1 based on hydrogel and liposome, special
Sign is that the derivative of chitosan described in step 2 is hydroxyethyl chitosan or carboxyetbyl chitosan.
7. the preparation method of the composite drug-loaded delivery materials according to claim 1 based on hydrogel and liposome, special
Sign is that polyethylene glycol described in step 2 is the polyethylene glycol that aldehyde radical is end group.
8. the preparation method of the composite drug-loaded delivery materials according to claim 1 based on hydrogel and liposome, special
Sign is that the molecular weight ranges of chitosan described in step 2 are 1000~100kDa, and the molecular weight ranges of polyethylene glycol are
500~1000kDa.
9. the preparation method of the composite drug-loaded delivery materials according to claim 1 based on hydrogel and liposome, special
Sign is that composite drug-loaded delivery materials formed in step 2, final concentration 10~100mg/mL of range of chitosan solution gather
The final concentration range of ethylene glycol solution is 10~500mg/mL, and the concentration range of liposome is 1~20wt%.
10. the preparation method of the composite drug-loaded delivery materials according to claim 1 based on hydrogel and liposome, special
Sign is that time of repose described in step 2 is 0.5~5min.
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Cited By (6)
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| CN111035801A (en) * | 2020-01-14 | 2020-04-21 | 青岛科技大学 | Silver nanocluster based chitosan hydrogel dressing and preparation method and application thereof |
| CN111317709A (en) * | 2020-03-20 | 2020-06-23 | 西安理工大学 | Injectable dual-drug-loaded composite chitosan hydrogel and preparation method thereof |
| CN112121003A (en) * | 2020-09-29 | 2020-12-25 | 江苏集萃新型药物制剂技术研究所有限公司 | Drug-carrying material of sustained-release preparation, composition of drug-carrying material, sustained-release preparation and preparation method of sustained-release preparation |
| CN113018249A (en) * | 2021-02-20 | 2021-06-25 | 浙江大学 | Oral sustained-release gel for treating candidiasis and preparation method thereof |
| CN114699562A (en) * | 2022-02-28 | 2022-07-05 | 南方科技大学 | Hydrogel and preparation method and application thereof |
| CN115737535A (en) * | 2022-08-19 | 2023-03-07 | 西北工业大学 | Controllable degradable nano composite gel and preparation method and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111317709A (en) * | 2020-03-20 | 2020-06-23 | 西安理工大学 | Injectable dual-drug-loaded composite chitosan hydrogel and preparation method thereof |
| CN111317709B (en) * | 2020-03-20 | 2023-03-24 | 西安理工大学 | Injectable dual-drug-loaded composite chitosan hydrogel and preparation method thereof |
| CN112121003A (en) * | 2020-09-29 | 2020-12-25 | 江苏集萃新型药物制剂技术研究所有限公司 | Drug-carrying material of sustained-release preparation, composition of drug-carrying material, sustained-release preparation and preparation method of sustained-release preparation |
| CN112121003B (en) * | 2020-09-29 | 2022-02-01 | 江苏集萃新型药物制剂技术研究所有限公司 | Drug-carrying material of sustained-release preparation, composition of drug-carrying material, sustained-release preparation and preparation method of sustained-release preparation |
| CN113018249A (en) * | 2021-02-20 | 2021-06-25 | 浙江大学 | Oral sustained-release gel for treating candidiasis and preparation method thereof |
| CN113018249B (en) * | 2021-02-20 | 2023-01-03 | 浙江大学 | Oral sustained-release gel for treating candidiasis and preparation method thereof |
| CN114699562A (en) * | 2022-02-28 | 2022-07-05 | 南方科技大学 | Hydrogel and preparation method and application thereof |
| CN115737535A (en) * | 2022-08-19 | 2023-03-07 | 西北工业大学 | Controllable degradable nano composite gel and preparation method and application thereof |
| CN115737535B (en) * | 2022-08-19 | 2023-09-01 | 西北工业大学 | Controllably degradable nano composite gel and preparation method and application thereof |
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