Alginate‐Boronic Acid: pH‐Triggered Bioinspired Glue for Hydrogel Assembly
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Abstract The development of bioadhesives has become an emerging research field for tissue sealants, wound dressings, and hemostatic agents. However, assembling hydrogels using bioadhesive‐mediated attachment remains a challenging task. Significantly high water content (>90%) in hydrogels compared to that of biological tissues is the main cause of failure. Considering that hydrogels are primary testing scaffolds mimicking in vivo environments, developing strategies to assemble hydrogels that exhibit diverse properties is important. Self‐healing gels have been reported, but such gels often lack biocompatibility, and two gel pieces should be identical in chemistry for assembly, thus not allowing co‐existence of diverse biological environments. Herein, a mussel‐mimetic cis ‐diol‐based adhesive, alginate‐boronic acid, that exhibits pH‐responsive curing from a viscoelastic solution to soft gels is developed. Associated mechanisms are that 1) polymeric diffusion occurs at interfaces utilizing intrinsic high water content; 2) the conjugated cis ‐diols strongly interact/entangle with hydrogel chains; 3) curing processes begin by a slight increase in pH, resulting in robust attachment of diverse types of hydrogel building blocks for assembly. The findings obtained with alginate‐boronic acid glues suggest a rational design principle to attach diverse hydrogel building blocks to provide platforms mimicking in vivo environments.Keywords:
Boronic acid
Biocompatibility
Wound dressing
Hydrogels are required to have high mechanical properties, biocompatibility, and an easy fabrication process for biomedical applications. Double-network hydrogels, although strong, are limited because of the complicated preparation steps and toxic materials involved. In this study, we report a simple method to prepare tough, in situ forming polyethylene glycol (PEG)-agarose double-network (PEG-agarose DN) hydrogels with good biocompatibility. The hydrogels display excellent mechanical strength. Because of the easily in situ forming method, the resulting hydrogels can be molded into any form as needed. In vitro and in vivo experiments illustrate that the hydrogels exhibit satisfactory biocompatibility, and cells can attach and spread on the hydrogels. Furthermore, the residual amino groups in the network can also be functionalized for various biomedical applications in tissue engineering and cell research.
Biocompatibility
Agarose
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Objective To systematically introduce the classification and properties of bioadhesive materials,the mechanisms of bioadhesion,the factors that influence the bioadhesive behavior,the evaluation methods for bioadhesion,the application of bioadhesive materials in pharmaceutical dosage forms and the problems existed accordingly. Methods Consult the recent journals and books,and make integration. Results The bioadhesive drug delivery system is the interest of many pharmaceutical researchers. However,the number of bioadhesive materials with satisfied quality is far less enough,the mechanisms of bioadhesion are still not quite clear,and the methods for bioadhesion evaluation leave much room to improve. Conclusions Bioadhesive materials shall have a very good prospect in the drug delivery system.
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Study on bioadhesion of 5-fluorouracil gastric bioadhesive tablets is the main aim. The bioadhesive force was evaluated by a self-made apparatus, and compared the force of the different formulations. In the same time, the content of swelling and expansion of tablets were also studied. The findings show that the bioadhesion force and the content of swelling and expansion of tablets were different from various formulations. The bioadhesion force, content of swelling and expansion of tablets also were criterions as the reference.
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Chitosan is currently proposed to be one of the most promising polymers in wound dressing development. Our research focuses on its potential as a vehicle for nano-delivery systems destined for burn therapy. One of the most important features of wound dressing is its bioadhesion to the wounded site. We compared the bioadhesive properties of chitosan with those of Carbopol, a synthetic origin polymer. Chitosan-based hydrogels of different molecular weights were first analyzed by texture analysis for gel cohesiveness, adhesiveness and hardness. In vitro release studies showed no difference in release of model antimicrobial drug from the different hydrogel formulations. Bioadhesion tests were performed on pig ear skin and the detachment force, necessary to remove the die from the skin, and the amount of remaining formulation on the skin were determined. Although no significant difference regarding detachment force could be seen between Carbopol-based and chitosan-based formulations, almost double the amount of chitosan formulation remained on the skin as compared to Carbopol formulations. The findings confirmed the great potential of chitosan-based delivery systems in advanced wound therapy. Moreover, results suggest that formulation retention on the ex vivo skin samples could provide deeper insight on formulation bioadhesiveness than the determination of detachment force.
Wound dressing
Antimicrobial drug
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Bioadhesion could lead to the solution of bioavailability problems resulting from a too short stay of the pharmaceutical dosage form at the absorption or activity level of the active ingredient. Bioadhesion stages are: intimate contact resulting from a good wetting of the bioadhesion surface and the swelling of the bioadhesive polymer, then penetration of the bioadhesive into the crevice of the tissue surface or interpenetration of bioadhesive chains with those of the mucus, and finally low chemical bonds. date, the most important bioadhesive polymers are polycarbophil a Carbopol 934. Methods of studying bioadhesion are described as well as the existing bioadhesive dosage forms.
Mucoadhesion
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Biocompatibility
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Oral bioadhesive particulate system for drug delivery can delay the drug staying on epthical cell and improve the bioavailability of drug by using bioadhesive polymers.The aim of this article is to present bioadhesive polymers,preparation methods and evaluation methods of this system.
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The development of biocompatible and easy to apply bone adhesives with significant adhesion performance under typical physiological conditions is currently considered one of the main challenges in bone tissue repair. Currently, commercially available materials, such as polymethylmethacrylate, fail to provide sufficient biocompatibility on the surroundings of the fracture, which in turn largely limits tissue repair. Chitosan, a widely studied natural polysaccharide, not only presents desirable biocompatibility, but also promising adhesive properties. Consequently, here we aimed to develop a chitosan-based bioadhesive with superior adhesiveness and enhanced biocompatibility. This was achieved by the chemical modification of chitosan's main backbone with methacryloyl groups that provide photoresponsiveness to tune the hydrogel's crosslinking level and consequently, mechanical properties.
Polymethyl methacrylate
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The novel bioadhesive drug de livery systems have become very promising because of their advantages in targeti ng, extended and controlled release. Of those, the lectin-mediated bioadhesive delivery system has specific targeting. And the particulate preparation can impr ove drug's stability and control drug release. The above two reasons cause the l ectin-mediated bioadhesive particulate preparation to gain the most extensive a ttention. The current reviews focus on the second-generation bioadhesive mechan isms, bioadhesive materials, influence factors, their applications and future tr ends.
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Studying on bioadhesion of Huperzine A gastrointestinal bioadhesive tablets is the main aim. The bioadhesive force was evaluated by a self-made apparatus, and compared the force between different bioadhesive tablets and gastric or intestinal mucosa. In the same time, the content of swelling and expansion of tablets were also studied. The findings show the bioadhesion force of tablets on gastric mucosa is far smaller than that on intestinal, and the force of bioadhesive tablets is larger than that of the blank.
Huperzine A
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