Advanced molecular design of biopolymers for transmucosal and intracellular delivery of chemotherapeutic agents and biological therapeutics
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Biocompatibility
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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The relatively weak mechanical properties of hydrogels remain a major drawback for their application as load-bearing tissue scaffolds. Previously, we developed cell-laden double-network (DN) hydrogels that were composed of photocrosslinkable gellan gum (GG) and gelatin. Further research into the materials as tissue scaffolds determined that the strength of the DN hydrogels decreased when they were prepared at cell-compatible conditions, and the encapsulated cells in the DN hydrogels did not function as well as they did in gelatin hydrogels. In this work, we developed microgel-reinforced (MR) hydrogels from the same two polymers, which have better mechanical strength and biological properties in comparison to the DN hydrogels. The MR hydrogels were prepared by incorporating stiff GG microgels into soft and ductile gelatin hydrogels. The MR hydrogels prepared at cell-compatible conditions exhibited higher strength than the DN hydrogels and the gelatin hydrogels, the highest strength being 2.8 times that of the gelatin hydrogels. MC3T3-E1 preosteoblasts encapsulated in MR hydrogels exhibited as high metabolic activity as in gelatin hydrogels, which is significantly higher than that in the DN hydrogels. The measurement of alkaline phosphatase (ALP) activity and the amount of mineralization showed that osteogenic behavior of MC3T3-E1 cells was as much facilitated in the MR hydrogels as in the gelatin hydrogels, while it was not as much facilitated in the DN hydrogels. These results suggest that the MR hydrogels could be a better alternative to the DN hydrogels and have great potential as load-bearing tissue scaffolds.
Gelatin
Gellan gum
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Novel Polymerized Ionic Liquids (PILs)-based Hydrogels as Innovative Drug Delivery Systems are presented. The
embedding of drugs in hydrogels enables the “smart” delivery of bioactive molecules from drugs for an oral route of
administration. Therefore, a high mechanical strength as well as a favorable pH-dependent swelling behavior is required
which is shown in this study. A mechanical compression of PILs-based hydrogels up to 98.5% and a high swelling
behavior of poly(VEImBr) hydrogels in a solution with a high pH value is achieved. A significant lower swelling is
achieved in a solution with a lower pH value.
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Abstract Novel enzyme‐based hydrogels for drug delivery were prepared by combining dextran with 5,5′‐azodisalicylic acid using isophorone diisocyanate as the crosslinking agent. The structure of the resultant dextran/5,5′‐azodisalicylic acid hydrogels was determined by infrared spectra, and the properties of the hydrogels were characterized by swelling measurements and scanning electron microscopy analysis. It was found that changing the concentration of 5,5′‐azodisalicylic acid affected the crosslinking density of the hydrogels and resulted in significant differences in the water swelling property and degradability of the hydrogels. Compared with their degradability, the degradation of the hydrogels seemed to be more pronounced by azoreductase in cecum content medium than that by hydrolysis in phosphate buffer solution (PBS). Also, the release rate of the protein in cecum content medium was faster than that in PBS. Attributing to the results of the resultant hydrogels described earlier, it could be concluded that dextran/5,5′‐azodisalicylic acid hydrogels could be used as a potential enzyme‐based carrier for colon‐specific drug delivery. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Dextranase
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Ordered mesoporous materials have been widely employed as carriers for controlled drug release due to their high specific surface areas,pore volumes and regulated pore channels.The controlled drug release capacities of ordered mesoporous materials can be improved upon surface modification,such as drug loading amount and enhancement and drug release rate reduction.The controlled drug release can improve the drug persistent efficacy and therapeutic efficiency,and achieve targeted drug delivery.Different ordered mesoporous materials as carriers for controlled drug release and influence factors are reviewed,and their application prospects are predicted.
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The relatively weak mechanical properties of hydrogels remain a major drawback for their application as load-bearing tissue scaffolds. Previously, we developed cell-laden double-network (DN) hydrogels that were composed of photocrosslinkable gellan gum (GG) and gelatin. Further research into the materials as tissue scaffolds determined that the strength of the DN hydrogels decreased when they were prepared at cell-compatible conditions, and the encapsulated cells in the DN hydrogels did not function as well as they did in gelatin hydrogels. In this work, we developed microgel-reinforced (MR) hydrogels from the same two polymers, which have better mechanical strength and biological properties in comparison to the DN hydrogels. The MR hydrogels were prepared by incorporating stiff GG microgels into soft and ductile gelatin hydrogels. The MR hydrogels prepared at cell-compatible conditions exhibited higher strength than the DN hydrogels and the gelatin hydrogels, the highest strength being 2.8 times that of the gelatin hydrogels. MC3T3-E1 preosteoblasts encapsulated in MR hydrogels exhibited as high metabolic activity as in gelatin hydrogels, which is significantly higher than that in the DN hydrogels. The measurement of alkaline phosphatase (ALP) activity and the amount of mineralization showed that osteogenic behavior of MC3T3-E1 cells was as much facilitated in the MR hydrogels as in the gelatin hydrogels, while it was not as much facilitated in the DN hydrogels. These results suggest that the MR hydrogels could be a better alternative to the DN hydrogels and have great potential as load-bearing tissue scaffolds.
Gelatin
Gellan gum
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This paper introduces a new delivery system for rapid and controlled drug release. Mixture of hydrophilic, (poly vinyl alcohol, PVA, and randomly methylated beta-cyclodextrin, RM beta-CD), and hydrophobic (poly D,L-lactide, PLA, and poly D,L-lactide-co-glycoside, PLGA) polymers were electrospun to make a multi-layered/multicomponent nanofiber mat. The release characteristics of the drug were modified using the layer by layer approach to help compensate the limitation of the individual materials. Incorporation of RM beta-CD to the PVA solution was able to significantly decrease the degradation rate of the resulting fiber mat from a few weeks to a few seconds. Hydrophilic polymer mat (PVA-RM beta-CD) can dissolve in the release media instantly and provide rapid release of the drug. This characteristic makes such carriers suitable as sublingual delivery systems in the treatment of acute disorders. Polyesters, PLA and PLGA, can control drug release via hydrolysis of the polymer and provide sustained and controlled release of the drug. Blends of these hydrophilic and hydrophobic polymers can effectively prolong drug release and decrease physiological toxicity resulting from fast release of drugs. These carriers may be suitable for the treatment of chronic disease where sustained release of the drug is required.
Vinyl alcohol
PLGA
Electrospinning
Beta-Cyclodextrins
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Cell encapsulation
Liberation
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In first unit of running was described the properties, method the obtention and kinds sensitive on factors such how the temperature, pH, the electrolytes, the chosen substances, light, of hydrogels and hydrogel delivery systems. The following study is a review of literature related to application of hydrogel as healing substances carriers, possibility of application of hydrogels in oral, applied on skin and the rectal, vaginal systems of release, applied on nasal as well as passed to eyes and parenteral. The utilization the hydrogels in construction the new systems of release the substance allows to remain the aspect ratio time of substance at the application place, the obtainment of prolonged release the medicine, by parallel of applied dose and the system undesirable effects. The hydrogels on the basis of were received the form of medicine about controlled release the substance, bioadhesive drug carriers as well targetable devices of therapeutic agents.
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