This study aimed to develop a pH-responsive folic acid-grafted organic/inorganic hybrid nanocomposite system for site-selective oral delivery of therapeutic antibodies. A folic acid-grafted aminoclay(FA-AC) was prepar...This study aimed to develop a pH-responsive folic acid-grafted organic/inorganic hybrid nanocomposite system for site-selective oral delivery of therapeutic antibodies. A folic acid-grafted aminoclay(FA-AC) was prepared via an in situ sol-gel method. Then, a drug-loaded nanocomplex was prepared via the electrostatic interaction of FA-AC with infliximab(IFX), a model antibody, and coated with Eudragit? S100(EFA-AC-IFX). FA-AC exhibited favorable profiles as a drug carrier including low cytotoxicity, good target selectivity, and capability to form a nanocomplex with negatively charged macromolecules. A pH-responsive FA-AC-based nanocomplex containing IFX(EFA-AC-IFX) was also obtained in a narrow size distribution with high entrapment efficiency(>87%). The conformational stability of IFX entrapped in EFA-AC-IFX was well maintained in the presence of proteolytic enzymes. EFA-ACIFX exhibited pH-dependent drug release, minimizing premature drug release in gastric conditions and the upper intestine. Accordingly, oral administration of EFA-AC-IFX to colitis-induced mice was effective in alleviating the progression of ulcerative colitis, while oral IFX solution had no efficacy. These results suggest that a pH-responsive FA-AC-based nanocomposite system can be a new platform for the site-selective oral delivery of therapeutic antibodies.展开更多
Compression coated tablets for oral colon specific delivery systems were developed with a mixture polysaccharide of konjac glucomannan(KGM)and xanthan gum(XG)as the compression coat.Diffusion of cimetidine from compre...Compression coated tablets for oral colon specific delivery systems were developed with a mixture polysaccharide of konjac glucomannan(KGM)and xanthan gum(XG)as the compression coat.Diffusion of cimetidine from compression coated tablets was investigated by release experiment in Vitro.0.22U/mLβ-mannanase was applied in the mimic colon solution.The structure of the mixture polysaccharide was studied by an atomic force microscope(AFM).The experimental results indicate that a KGM70 tablet with a 0.4 g coat is of good design,due to a less than 5%drug loss in the mimic upper gastrointestinal solution by the synergistic interaction between XG and KGM,and due to about 50%cumulative release in the mimic colon solution by degradation after 24 hours.The release mechanism and model are discussed based on different periods of drug release including the delay of the drug,the constant release without an enzyme and the delay of degradation.Under hydrolysis byβ-mannanase,drug release from the tablet with KGM coat shows an exponential increase,while that from the dosage with the mixture polysaccharide coat is an approximately zero-order process in which the constant release rate relates to the release velocity of a non-degraded system,the content of KGM within the coat and the average molecular weight ratio of KGM to XG.It was found that XG was the framework of the polysaccharide mixtures by AFM,which is similar to the analysis results from experiments on drug release.展开更多
Aquatic products are considered a potential source of novel bioactive proteins,which are used as therapeutic drugs for the treatment of different diseases(such as oxidative stress,immunocompromised,and inflammation),a...Aquatic products are considered a potential source of novel bioactive proteins,which are used as therapeutic drugs for the treatment of different diseases(such as oxidative stress,immunocompromised,and inflammation),as well as nutraceuticals and cosmetics.However,the physical and chemical properties of proteins are unstable,and they are easily denatured by the influence of external high temperature and polar pH during processing,resulting in the loss of their functional activity.Herein,Fenneropenaeus chinensis water-soluble protein(FCWP)and Lateolabrax japonicus water-soluble protein(LJWP)were encapsulated within spherical biopolymer microgels composed of pectin and chitosan produced by the microfluidic device.The encapsulated samples remained inside the microgels when they were exposed to upper gastrointestinal but were released when they were exposed to simulated colonic fluid due to the hydrolysis effect by enzymes secreted by the colonic microflora.The results showed that microgels improve the thermal stability of FCWP and LJWP due to the interaction between polysaccharides and proteins in the microgels.In addition,microgels encapsulation did not affect the antioxidant and immunoenhancing activities of FCWP and LJWP.In summary,these microgels are suitable for oral colon-specific delivery in functional foods and supplements.展开更多
基金supported by National Research Foundation of Korea (NRF)South Korea grant funded by the Korea government(MSIT)(Nos. 2019R1A2C2004873 and 2018R1A5A2023127)the BK21 FOUR program through the National Research Foundation (NRF) funded by the Ministry of Education of Korea
文摘This study aimed to develop a pH-responsive folic acid-grafted organic/inorganic hybrid nanocomposite system for site-selective oral delivery of therapeutic antibodies. A folic acid-grafted aminoclay(FA-AC) was prepared via an in situ sol-gel method. Then, a drug-loaded nanocomplex was prepared via the electrostatic interaction of FA-AC with infliximab(IFX), a model antibody, and coated with Eudragit? S100(EFA-AC-IFX). FA-AC exhibited favorable profiles as a drug carrier including low cytotoxicity, good target selectivity, and capability to form a nanocomplex with negatively charged macromolecules. A pH-responsive FA-AC-based nanocomplex containing IFX(EFA-AC-IFX) was also obtained in a narrow size distribution with high entrapment efficiency(>87%). The conformational stability of IFX entrapped in EFA-AC-IFX was well maintained in the presence of proteolytic enzymes. EFA-ACIFX exhibited pH-dependent drug release, minimizing premature drug release in gastric conditions and the upper intestine. Accordingly, oral administration of EFA-AC-IFX to colitis-induced mice was effective in alleviating the progression of ulcerative colitis, while oral IFX solution had no efficacy. These results suggest that a pH-responsive FA-AC-based nanocomposite system can be a new platform for the site-selective oral delivery of therapeutic antibodies.
基金the financial support from Grand project of Tianjin City,China(No.07ZCZDGX19600).
文摘Compression coated tablets for oral colon specific delivery systems were developed with a mixture polysaccharide of konjac glucomannan(KGM)and xanthan gum(XG)as the compression coat.Diffusion of cimetidine from compression coated tablets was investigated by release experiment in Vitro.0.22U/mLβ-mannanase was applied in the mimic colon solution.The structure of the mixture polysaccharide was studied by an atomic force microscope(AFM).The experimental results indicate that a KGM70 tablet with a 0.4 g coat is of good design,due to a less than 5%drug loss in the mimic upper gastrointestinal solution by the synergistic interaction between XG and KGM,and due to about 50%cumulative release in the mimic colon solution by degradation after 24 hours.The release mechanism and model are discussed based on different periods of drug release including the delay of the drug,the constant release without an enzyme and the delay of degradation.Under hydrolysis byβ-mannanase,drug release from the tablet with KGM coat shows an exponential increase,while that from the dosage with the mixture polysaccharide coat is an approximately zero-order process in which the constant release rate relates to the release velocity of a non-degraded system,the content of KGM within the coat and the average molecular weight ratio of KGM to XG.It was found that XG was the framework of the polysaccharide mixtures by AFM,which is similar to the analysis results from experiments on drug release.
基金financed by the National Key Research and Development Program of China(2022YFF1100603)the Key Research and Development Program of Shandong Province(2021SFGC1205).
文摘Aquatic products are considered a potential source of novel bioactive proteins,which are used as therapeutic drugs for the treatment of different diseases(such as oxidative stress,immunocompromised,and inflammation),as well as nutraceuticals and cosmetics.However,the physical and chemical properties of proteins are unstable,and they are easily denatured by the influence of external high temperature and polar pH during processing,resulting in the loss of their functional activity.Herein,Fenneropenaeus chinensis water-soluble protein(FCWP)and Lateolabrax japonicus water-soluble protein(LJWP)were encapsulated within spherical biopolymer microgels composed of pectin and chitosan produced by the microfluidic device.The encapsulated samples remained inside the microgels when they were exposed to upper gastrointestinal but were released when they were exposed to simulated colonic fluid due to the hydrolysis effect by enzymes secreted by the colonic microflora.The results showed that microgels improve the thermal stability of FCWP and LJWP due to the interaction between polysaccharides and proteins in the microgels.In addition,microgels encapsulation did not affect the antioxidant and immunoenhancing activities of FCWP and LJWP.In summary,these microgels are suitable for oral colon-specific delivery in functional foods and supplements.
