CN105254932A - Interpenetrating network hydrogel based on alginic acid and oligopeptide and preparation method thereof - Google Patents
Interpenetrating network hydrogel based on alginic acid and oligopeptide and preparation method thereof Download PDFInfo
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- CN105254932A CN105254932A CN201510725704.XA CN201510725704A CN105254932A CN 105254932 A CN105254932 A CN 105254932A CN 201510725704 A CN201510725704 A CN 201510725704A CN 105254932 A CN105254932 A CN 105254932A
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Abstract
The invention discloses an interpenetrating network hydrogel based on alginic acid and oligopeptide and a preparation method thereof. The interpenetrating network hydrogel is characterized in that two materials with different gelatinization mechanism properties are combined. A preparation process comprises the following two steps: (1) by utilizing temperature responsive properties of an oligopeptide gel behavior, mixing sodium alginate and the oligopeptide at a temperature higher than a critical gel temperature, and firstly, obtaining first network polysaccharide gel by adding multivalent metal ions; (2) cooling the first network polysaccharide gel to be lower than the critical gel temperature, wherein the oligopeptide is self-assembled between first networks through pi-pi accumulation effect and a hydrogen bond, and is further gelatinized to obtain a second network. The interpenetrating network hydrogel disclosed by the invention has a more dense network structure and higher mechanical strength and the content is not easy to leak; a multi-responsiveness function unit is convenient to design and the releasing of medicines is controlled by using different physical stimulations.
Description
Technical field
The present invention relates to polymeric material field.Be specifically related to a kind of interpenetration network hydrogel based on Lalgine and small peptide and preparation method thereof.
Background technology
Hydrogel, as the high water-keeping material of a kind of high water suction, is widely used in the numerous areas such as multiple daily-use chemical industry, agricultural, medicine, food.But the embedding techniques of hydrogel in above field, also exists some problems, when such as embedding hydrophilic small molecules material, because molecular mass is little, good water solubility, there is the deficiencies such as embedding efficiency is low, Co ntrolled release is difficult.Interpenetrating(polymer)networks (interpenetratingnetwork, IPN) hydrogel has finer and close network structure, and its container is not easy to reveal, and is convenient to design multiple response sexual function unit, realizes utilizing different physical stimulation Drug controlled release.Lalgine is a kind of common hydrogel carrier material, but because of its aperture comparatively large, be difficult to the controlled release accomplishing small-molecule drug, be mainly limited to the slowly-releasing of macromolecular drug at present.Small peptide hydrogel is the class novel intelligent response biological medicine material that developed recently gets up, but its physical strength is low, is easily destroyed.Lalgine is mainly through ion complexation and polyvalent metal ion generation gelation, and aromaticity polypeptide then interacts mainly through hydrogen bond and π-π and carries out beta sheet, and then forms nanofiber and macroscopic hydrogel.But so far, the interpenetrating(polymer)networks gel based on Lalgine and small peptide bi-material not yet has been reported, and processing condition, functional property need deep exploitation.
Summary of the invention
The object of this invention is to provide a kind of interpenetration network hydrogel based on Lalgine and small peptide and its preparation method and application.
In the present invention, the feature of interpenetration network hydrogel is the bi-material coupling possessing different gelation mechanism character.Wherein, Lalgine adopts multivalent metallic ion crosslinking gelation mechanism and small peptide to adopt by pi-pi accumulation effect and H-bonding self-assembly gelation mechanism.
Polyvalent metal ion of the present invention comprises divalent-metal ion Ca
2+, Mg
2+, and Ba
2+; Described small peptide comprises Fmoc-F, Fmoc-FF, Fmoc-FFF, Fmoc-Y, Nap-FF, Nap-FFKY, Fc-F, or other is by the aromaticity small peptide of pi-pi accumulation effect and H-bonding self-assembly gelation.
The preparation method of interpenetration network hydrogel comprises following two steps: (1) utilizes the temperature-responsive of small peptide gel behavior, at the above mixing sodium alginate of its critical gelling temp and small peptide, first obtain first network polysaccharide gel by adding divalent-metal ion; (2) be then cooled to below critical gelling temp, small peptide obtains second network by pi-pi accumulation and the further gelation of H-bonding self-assembly between first network.
In the step of aforesaid method, the concentration of sodium alginate is 1% ~ 5%, and the concentration of metal ion is 0.1mol/L ~ 3mol/L, and the concentration of small peptide is 1mg/mL ~ 20mg/mL.In described experiment condition, the critical gelling temp of small peptide is generally 30 DEG C ~ 50 DEG C, therefore before adding divalent-metal ion in described step (1), the temperature condition of sodium alginate and small peptide mixing solutions is more than 50 DEG C, and after adding divalent-metal ion in described step (2), the temperature condition of sodium alginate and small peptide mixing solutions is less than 30 DEG C.
The preparation principle of interpenetration network hydrogel of the present invention is ingenious utilization and integrates the relatively independent single gel of two kinds of assembly mechanisms, builds novel macromolecule/small molecules interpenetrating(polymer)networks gel.Its constitutional features is, good by biocompatibility, to have pH responsiveness anionic macromole (being specially Lalgine) and the aromaticity short peptide molecules (such as containing phenylalanine, tyrosine sequence) with temperature-responsive form.Anionic polysaccharide is mainly through ion complexation and polyvalent metal ion generation gelation, and aromaticity small peptide then interacts mainly through hydrogen bond and π-π and carries out beta sheet, and then forms nanofiber and macroscopic hydrogel.
The preparation principle of interpenetration network hydrogel of the present invention meets following 2 points: first, under short peptide molecules exists and on the critical gelling temp of small peptide, and preparation polysaccharide hydrogel; Then, reduce temperature, short peptide molecules generation gelation interts at polysaccharide hydrogel inside formation second network.
From aforesaid operations step, the technology of the present invention mild condition, does not relate to harsh reaction conditions as High Temperature High Pressure etc., is conducive to practical application and promotes.Research finds that the physical strength of interpenetration network hydrogel of the present invention is far away higher than single gel.Fig. 1 is the stream change characterization result of the interpenetration network hydrogel based on Lalgine/Fmoc-Y composition, can find out that the Young's modulus (G ') of interpenetration network hydrogel can reach 10000Pa, and the G ' of the Lalgine gel (ALG) of calcium ion crosslinking is about 700Pa, the G ' of Fmoc-Y gel is about 1000Pa.
The interpenetration network hydrogel utilizing the present invention to prepare can be directly used in embedding and the Co ntrolled release of hydrophilic small molecules material.Hydrophilic small molecules material of the present invention comprises rhodamine B, 5-aminosalicylic acid and 5 FU 5 fluorouracil.
Fig. 2 is based on the cumulative release kinetic curve of rhodamine B in the buffer release medium of pH2.0 and pH7.4 in the IPN gel of Lalgine/Fmoc-Y composition at 37 DEG C.As can be seen from Figure 2, when no matter being pH2.0 or pH7.4, IPN has long sustained release property to rhodamine B, and rhodamine B is slower than pH7.4 in the release of pH2.0.Otherwise rhodamine B is very fast to be diffused out from single ALG gel, having and obviously prominently releasing phenomenon, under the concentration conditions of same rhodamine in addition, single Fmoc-Y can not form gel.
When Fig. 3 is 37 DEG C, based on the cumulative release kinetic curve of 5-aminosalicylic acid in pH2.0-pH7.4 damping fluid continuous release medium in the IPN gel of Lalgine/Fmoc-Y composition.As can be seen from Figure 3, compare single ALG gel and single Fmoc-Y gel, 5-aminosalicylic acid has better sustained release property in IPN hydrogel.
The invention has the advantages that: 1) preparation technology is simple, mild condition; 2) physical strength of the interpenetration network hydrogel prepared by is higher than single hydrogel; 3) interpenetration network hydrogel prepared by can be used for embedding and the Co ntrolled release of hydrophilic small molecules material.
Accompanying drawing explanation
Fig. 1. the stream based on the interpenetration network hydrogel of Lalgine/Fmoc-Y composition becomes characterization result
Fig. 2. based on the interpenetration network hydrogel of Lalgine/Fmoc-Y composition to the Co ntrolled release of rhodamine B
Fig. 3. based on the interpenetration network hydrogel of Lalgine/Fmoc-Y composition to the Co ntrolled release of 5-aminosalicylic acid
Embodiment
Following examples are intended to the present invention instead of limitation of the invention further are described.
Embodiment 1.
Based on the interpenetration network hydrogel of Lalgine/Fmoc-Y composition
First, preheating sodium alginate aqueous solution (15mg/mL), to 60 DEG C, then adds DMSO solution (100mg/mL) the 15 μ L of Fmoc-Y, and heat obtains the solution of transparent and homogeneous altogether, then adds 100 μ LCaCl
2solution (0.2mol/L), quick oscillation makes its initial gelatinization, is then cooled to room temperature and places 24h, prepares Lalgine/Fmoc-Y small peptide interpenetration network hydrogel.
Embodiment 2.
Based on the interpenetration network hydrogel of Lalgine/Fmoc-Y composition to the embedding of rhodamine B
First, preheating sodium alginate (15mg/mL) and rhodamine B (1mg/mL) mixing solutions to 60 DEG C, then add DMSO solution (100mg/mL) the 15 μ L of Fmoc-Y, heat obtains the solution of transparent and homogeneous altogether, then adds 100 μ LCaCl
2solution (0.2mol/L), quick oscillation makes its initial gelatinization, is then cooled to room temperature and places 24h, prepares the Lalgine/Fmoc-Y small peptide interpenetration network hydrogel of embedding rhodamine B.
Embodiment 3.
Based on the interpenetration network hydrogel of Lalgine/Fmoc-Y composition to the embedding of 5-aminosalicylic acid
First, preheating sodium alginate (15mg/mL) and 5-aminosalicylic acid (1mg/mL) mixing solutions to 60 DEG C, then add DMSO solution (100mg/mL) the 15 μ L of Fmoc-Y, heat obtains the solution of transparent and homogeneous altogether, then adds 100 μ LCaCl
2solution (0.2mol/L), quick oscillation makes its initial gelatinization, is then cooled to room temperature and places 24h, prepares the Lalgine/Fmoc-Y small peptide interpenetration network hydrogel of embedding 5-aminosalicylic acid.
Embodiment 4.
Based on the interpenetration network hydrogel of Lalgine/Fmoc-Y composition to the embedding of 5 FU 5 fluorouracil
First, preheating sodium alginate (15mg/mL) and 5 FU 5 fluorouracil (1mg/mL) mixing solutions to 60 DEG C, then add DMSO solution (100mg/mL) the 15 μ L of Fmoc-Y, heat obtains the solution of transparent and homogeneous altogether, then adds 100 μ LCaCl
2solution (0.2mol/L), quick oscillation makes its initial gelatinization, is then cooled to room temperature and places 24h, prepares the Lalgine/Fmoc-Y small peptide interpenetration network hydrogel of embedding 5 FU 5 fluorouracil.
Embodiment 5.
Based on the interpenetration network hydrogel of Lalgine/Fmoc-F composition to the embedding of hydroaropic substance and Co ntrolled release
First, preheating sodium alginate (15mg/mL) and hydroaropic substance (comprise rhodamine B, 5-aminosalicylic acid and 5 FU 5 fluorouracil, 1mg/mL) mixing solutions to 60 DEG C, then DMSO solution (100mg/mL) the 15 μ L of Fmoc-F is added, heat obtains the solution of transparent and homogeneous altogether, add 100 μ LCaCl2 solution (0.2mol/L) again, quick oscillation makes its initial gelatinization, then be cooled to room temperature and place 24h, preparing the Lalgine/Fmoc-F small peptide interpenetration network hydrogel of embedding hydroaropic substance.
Claims (10)
1. interpenetration network hydrogel based on Lalgine and small peptide and preparation method thereof, is characterized in that the bi-material coupling possessing different gelation mechanism character.
2. wherein, Lalgine adopts polyvalent metal ion induced gelatination mechanism and small peptide to adopt by pi-pi accumulation effect and H-bonding self-assembly gelation mechanism.
3. according to claim 1, Lalgine can by divalent calcium ions, magnesium ion, barium ion crosslinked generation gelation, small peptide is Fmoc-F, Fmoc-FF, Fmoc-FFF, Fmoc-Y, Nap-FF, Nap-FFKY, Fc-F, or other is by the aromaticity small peptide of pi-pi accumulation effect and H-bonding self-assembly gelation.
4. according to claim 1, the preparation method of interpenetration network hydrogel comprises following two steps: (1) utilizes the temperature-responsive of small peptide gel behavior, at the above mixing sodium alginate of its critical gelling temp and small peptide, first obtain first network polysaccharide gel by adding polyvalent metal ion; (2) be then cooled to below critical gelling temp, small peptide obtains second network by pi-pi accumulation effect and the further gelation of H-bonding self-assembly between first network.
5. preparation method according to claim 3, is characterized in that: in described step (1), polyvalent metal ion is divalent-metal ion, comprises calcium ion, magnesium ion, barium ion.
6. the method for step (2) according to claim 3, it is characterized in that: described small peptide is Fmoc-F, Fmoc-FF, Fmoc-FFF, Fmoc-Y, Nap-FF, Nap-FFKY, Fc-F, or other is by the aromaticity small peptide of pi-pi accumulation effect and H-bonding self-assembly gelation.
7. preparation method according to claim 3, it is characterized in that the concentration of sodium alginate in described experiment condition is 1% ~ 5%, the concentration of metal ion is 0.1mol/L ~ 3mol/L, and the concentration of small peptide is 1mg/mL ~ 20mg/mL.
8. preparation method according to claim 3, is characterized in that in described experiment condition, critical gelling temp is 30 ~ 50 DEG C.
9. interpenetration network hydrogel according to claim 1 can be directly used in embedding and the Co ntrolled release of hydrophilic small molecules material.
10. according to claim 8, the hydrophilic small molecules material of interpenetration network hydrogel embedding comprises rhodamine B, 5-aminosalicylic acid and 5 FU 5 fluorouracil.
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Cited By (6)
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| CN106435831A (en) * | 2016-09-23 | 2017-02-22 | 青岛大学 | Preparing method for sodium alginate nanofiber based on self-assembly technology |
| CN107043465A (en) * | 2017-03-18 | 2017-08-15 | 华南理工大学 | A kind of urea groups pyrimidone modified gelatin injectable self-healing hydrogel and preparation method thereof |
| CN111494411A (en) * | 2020-05-21 | 2020-08-07 | 中国医学科学院放射医学研究所 | In-situ self-assembled tetravalent platinum drug and preparation method and application thereof |
| CN111821419A (en) * | 2020-07-31 | 2020-10-27 | 浙江大学 | Self-assembly polypeptide nano-carrier and preparation method and application thereof |
| CN114062467A (en) * | 2021-09-13 | 2022-02-18 | 浙江大学 | Flexible electronic skin based on peptide self-assembly supermolecule hydrogel and preparation method thereof |
| CN114699366A (en) * | 2022-05-17 | 2022-07-05 | 西安交通大学 | High-concentration loaded gel of adriamycin medicine and preparation method thereof |
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2015
- 2015-10-30 CN CN201510725704.XA patent/CN105254932A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106435831A (en) * | 2016-09-23 | 2017-02-22 | 青岛大学 | Preparing method for sodium alginate nanofiber based on self-assembly technology |
| CN107043465A (en) * | 2017-03-18 | 2017-08-15 | 华南理工大学 | A kind of urea groups pyrimidone modified gelatin injectable self-healing hydrogel and preparation method thereof |
| CN111494411A (en) * | 2020-05-21 | 2020-08-07 | 中国医学科学院放射医学研究所 | In-situ self-assembled tetravalent platinum drug and preparation method and application thereof |
| CN111821419A (en) * | 2020-07-31 | 2020-10-27 | 浙江大学 | Self-assembly polypeptide nano-carrier and preparation method and application thereof |
| CN114062467A (en) * | 2021-09-13 | 2022-02-18 | 浙江大学 | Flexible electronic skin based on peptide self-assembly supermolecule hydrogel and preparation method thereof |
| CN114062467B (en) * | 2021-09-13 | 2023-02-14 | 浙江大学 | Flexible electronic skin based on peptide self-assembly supermolecule hydrogel and preparation method thereof |
| CN114699366A (en) * | 2022-05-17 | 2022-07-05 | 西安交通大学 | High-concentration loaded gel of adriamycin medicine and preparation method thereof |
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