Despite the advent of biological products, such as anti-tumor necrosis factor-α monoclonal antibodies (infliximab and adalimumab), for treatment of moderate to severe cases of inflammatory bowel disease (I...Despite the advent of biological products, such as anti-tumor necrosis factor-α monoclonal antibodies (infliximab and adalimumab), for treatment of moderate to severe cases of inflammatory bowel disease (IBD), most patients depend upon aminosalicylates as the conventional treatment option. In recent years, the increased knowledge of complex pathophysiological processes underlying IBD has resulted in development of a number of newer pharmaceutical agents like low-molecular-weight heparin, omega-3 fatty acids, probiotics and innovative formulations such as high-dose, once-daily multi-matrix mesalamine, which are designed to minimize the inflammatory process through inhibition of different targets. Optimization of delivery of existing drugs to the colon using the prodrug approach is another attractive alternative that has been utilized and commercialized for 5-aminosalicylic acid (ASA) in the form of sulfasalazine, balsalazide, olsalazine and ipsalazine, but rarely for its positional isomer 4-ASA - a well-established antitubercular drug that is twice as potent as 5-ASA against IBD, and more specifically, ulcerative colitis. The present review focuses on the complete profile of 4-ASA and its advantages over 5-ASA and colon-targeting prodrugs reported so far for the management of IBD. The review also emphasizes the need for reappraisal of this promising but unexplored entity as a potential treatment option for IBD.展开更多
A series of cross-linked gels of Poly（N-isopropylacrylamide） [P（NIPAAm）] and Poly（methacr-ylic acid）[P（MAA）] homopolymers and P（NIPAAm-co-MAA） random copolymers were synthesized based on NIPAAm and MAA using...A series of cross-linked gels of Poly（N-isopropylacrylamide） [P（NIPAAm）] and Poly（methacr-ylic acid）[P（MAA）] homopolymers and P（NIPAAm-co-MAA） random copolymers were synthesized based on NIPAAm and MAA using 4,4-Bis-（methacryloylamino） azobenzene （BMAAB） as a cross-linker. The swelling behavior of these hydrogels in different pH buffer solutions was studied. The influential factors of the gels including composition of NIPAAm and MAA, pH and temperature upon swelling behavior were investigated. The obtained gels not only hold pH and thermometrical sensitivity, but also take on enzymatic sensitivity due to the cross-linker could be degraded by enzymes of colon. Swelling equilibrium degree of copolymers was very low in acidic medium, which could avoid drug releasing due to biggish swelling of carder in stomach. Hydrogels would partly swell owing to higher pH value in small intestine. When arrived in colon, hydrogels completely swelled, meanwhile, azoenzymes located would degrade azo-bonds of polymeric network and then drug released in colon.展开更多
AIM： To investigate the release of cyclodextrin-S-amino- salicylic acid （CyD-S-ASA） in cecum and colon. METHODS： An anti-inflammatory drug 5-ASA was conjugated onto the hydroxyl groups of α-, β- and γ-cydodextr...AIM： To investigate the release of cyclodextrin-S-amino- salicylic acid （CyD-S-ASA） in cecum and colon. METHODS： An anti-inflammatory drug 5-ASA was conjugated onto the hydroxyl groups of α-, β- and γ-cydodextrins （CyDs） through an ester linkage, and the in vivo drug release behavior of these prodrugs in rat＇ s gastrointestinal tract after the oral administration was investigated. RESULTS： The 5-ASA concentration in the rat＇s stomach and small intestine after the oral administration of CyD- 5-ASA conjugate was much lower than that after the oral administration of 5-ASA alone. The lower concentration was attributable to the passage of the conjugate through the stomach and small intestine without significant degradation or absorption, followed by the degradation of the conjugate site-specific in the cecum and colon. The oral administration of CyD-S-ASA resulted in lower plasma and urine concentration of 5-ASA than that of 5-ASA alone. CONCLUSION： CyD-5-ASA conjugates may be used as prodrugs for colon-specific drug delivery system.展开更多
A series of cross-linked hydrogels for colon-specific drug delivery were synthesized by graft copolymerization of Chitosan and acrylic acid using N, N＇-methylene-bis-（acrylamide） as a cross-linker. Their swelling b...A series of cross-linked hydrogels for colon-specific drug delivery were synthesized by graft copolymerization of Chitosan and acrylic acid using N, N＇-methylene-bis-（acrylamide） as a cross-linker. Their swelling behavior in different pH buffer solutions and colonic enzymatic degradability were studied. The obtained results show that these hydrogels have good pH sensitivity which can avoid drug release in stomach, and their swelling kinetics in stimulant intestinal environment follow second-order swelling kinetics equation. The factors influencing the swelling kinetics include the degree of cross-linking and the composition, which may control no release or a little amount release of drug inside the hydrogels in the small intestine by tailoring these factors. The gels are degradable by colonic enzymes and there is a correlativity between the degradation of networks and the swelling degree of the gels, which may trigger the release of drug in the colon. The hydrogels show a great potential for their application in oral colon-specific drug delivery system.展开更多
A colon-specific drug delivery system has great potential for the oral administration of colorectal cancer.However,the uncontrollable in vivo fate of liposomes makes their effectiveness for colonic location,and intrat...A colon-specific drug delivery system has great potential for the oral administration of colorectal cancer.However,the uncontrollable in vivo fate of liposomes makes their effectiveness for colonic location,and intratumoral accumulation remains unsatisfactory.Here,an oral colon-specific drug delivery system(CBS-CS@Lipo/Oxp/MTZ)was constructed by covalently conjugating Clostridium butyricum spores(CBS)with drugs loaded chitosan(CS)-coated liposomes,where the model chemotherapy drug oxaliplatin(Oxp)and anti-anaerobic bacteria agent metronidazole(MTZ)were loaded.Following oral administration,CBS germinated into Clostridium butyricum(CB)and colonized in the colon.Combined with colonic specificallyβ-glucosidase responsive degrading of CS,dual colon-specific release of liposomes was achieved.And the accumulation of liposomes at the CRC site furtherly increased by 2.68-fold.Simultaneously,the released liposomes penetrated deep tumor tissue via the permeation enhancement effect of CS to kill localized intratumoral bacteria.Collaborating with blocking the translocation of intestinal pathogenic bacteria from lumen to tumor with the gut microbiota modulation of CB,the intratumoral pathogenic bacteria were eliminated fundamentally,blocking their recruitment to immunosuppressive cells.Furtherly,synchronized with lipopolysaccharide(LPS)released from MTZ-induced dead Fusobacterium nucleatum and the tumor-associated antigens produced by Oxp-caused immunogenic dead cells,they jointly enhanced tumor infiltration of CD8^(+)T cells and reactivated robust antitumor immunity.展开更多
Pectin-chitosan complex was prepared as a candidate material for colon-specific capsule.First,the effects of beating on the properties of complex films were explored.Fourier transform infrared(FT-IR)spectroscopy was u...Pectin-chitosan complex was prepared as a candidate material for colon-specific capsule.First,the effects of beating on the properties of complex films were explored.Fourier transform infrared(FT-IR)spectroscopy was used to analyze the reaction mechanics,and an in vitro simulation experiment was performed to determine the degradation performance.Second,the capsule was prepared using pectin-chitosan complex as the main raw material;its targeting effect was evaluated and analyzed.Results indicated that the film became smooth and compact by beating.FT-IR data indicated that cross-linking occurred between the hydroxyl group of pectin and the amino group of chitosan to form a network structure.In vitro experiment showed that the pectin-chitosan complex film could not be degraded in the simulated gastric and intestinal fluids.However,pectin-chitosan complex could be degraded in the simulated colonic fluid,so it could be a potential candidate for colon-specific capsule.Because the complex has no ability for forming hard capsule,the carrageenan and starch were added to increase the flexibility,gelation,transparency and mechanical properties of the film.The preferred composition suitable for preparing the capsule was a mass ratio(2:1:1)of pectin-chitosan/carrageenan/starch mixture.The capsule showed excellent features in terms of shape,water content,and brittleness.The drug release rate reached 93.33%in colonic fluid for 1 h when bovine serum albumin was the model drug.Therefore,pectin-chitosan may be considered as a new material for colon-targeted capsule.展开更多
Ulcerative colitis(UC)is a common progressive inflammatory disease whose incidence has increased rapidly in recent years,and can develop into colorectal cancer in severe cases.There are currently no adequate or effect...Ulcerative colitis(UC)is a common progressive inflammatory disease whose incidence has increased rapidly in recent years,and can develop into colorectal cancer in severe cases.There are currently no adequate or effective treatments for UC due to the fact that some patients have found suboptimal results after repeated administration,while others have experienced adverse effects.With the rapid development of nanotechnology,developing innovative colon-targeting platforms is essential to improving efficacy,reducing side effects,and improving patient compliance.In this review,we summarize the pathophysiological characteristics of UC and the most recent status of numerous nanodrug delivery systems based on different targeting mechanisms in treating UC.Oral,intravenous,and rectal drug delivery nanoparticles targeting the colon are discussed,which can provide ideas for the design of colon-targeting nanoparticles for the treatment of colon diseases,especially for the treatment of UC.Last but not least,we provide a glimpse into the future of colon-targeted delivery systems,as well as future advancements in the field.展开更多
AIM: To investigate the permeability characteristics of rebamipide across intestinal mucosa, and examine the effects of some absorption enhancers on the permeability across the colonic tissue. Another purpose is to de...AIM: To investigate the permeability characteristics of rebamipide across intestinal mucosa, and examine the effects of some absorption enhancers on the permeability across the colonic tissue. Another purpose is to demonstrate the colon-specific delivery of rebamipide with or without absorption enhancers using chitosan capsule as a carrier. METHODS: The permeability of rebamipide was evaluated using an in vitro diffusion chamber system, and the effects of some absorption enhancers on the permeability via colon were further investigated. The release of rebamipide from chitosan or gelatin capsule was studied by Japan Pharmacopoeia rotating basket method. The colonic and plasma concentrations were analyzed by high performance liquid chromatography (HPLC) to evaluate colon-targeting action after oral administration of various dosage forms, and rebamipide with absorption enhancers in chitosan dosage forms. RESULTS: The permeability of rebamipide across the jejunal or ileal membranes was higher than the colonic membranes. Both sodium laurate (C12) and labrasol signifi cantly increased permeability across the colon membranes. On the other hand, the release of rebamipide from chitosan capsule was less than 10%totally within 6 h. The area under concentration-time profile of drug in the colon mucosa using chitosan capsules (AUCLI, 1 6011.2 ng·h/g) was 2.5 times and 4.4 times greater than using gelatin capsules and CMC suspension, respectively. Meanwhile, the area under concentration-time profile of drug in the plasma (AUCPL) was 1016.0 ng·h/mL for chitosan capsule, 1887.9 ng·h/mL for CMC suspension p and 2163.5 ng·h/mL for gelatin capsule. Overall, both AUCLI and AUCPL were increased when C12 was co-administrated, but the increase of AUCLI was much greater; the drug delivery index (DDI) was more than 1 compared with simple chitosan capsule group. CONCLUSION: There was a regional difference in the permeability of Rabamipide across the jejunum, ileum and the colon, and passive diffusion seems to be one of the major transport mechanisms of rebamipide. Absorption enhancers can increase the permeability of rebamipide across the colon tissue signifi cantly. In addition, chitosan capsule may be a useful carrier to deliver rebamipide to the colon specifi cally and the co-administration of C12 with rebamipide may also be very useful in local treatment.展开更多
The aim of this study was to evaluate the effect of coating of alginate-chitosan (AL:CS) beads on the colonic drug delivery. The AL:CS systems containing triamcinolone (TC) were coated with the HPMCP and Eudragit? L10...The aim of this study was to evaluate the effect of coating of alginate-chitosan (AL:CS) beads on the colonic drug delivery. The AL:CS systems containing triamcinolone (TC) were coated with the HPMCP and Eudragit? L100 by immersion and by spraying methods. The drug release profile in simulated colonic medium was determined using 5% human fecal content suspension in 0.01 N buffer solution, pH 6.8. The systems coated with HPMCP showed a lower rate of drug delivery in simulated enteric medium. The delivery profile in simulated colonic medium followed zero-order kinetic. The coated systems provided a promising drug-delivery profile for application in colonic drug delivery.展开更多
Due to its safety,convenience,low cost and good compliance,oral administration attracts lots of attention.However,the efficacy of many oral drugs is limited to their unsatisfactory bioavailability in the gastrointesti...Due to its safety,convenience,low cost and good compliance,oral administration attracts lots of attention.However,the efficacy of many oral drugs is limited to their unsatisfactory bioavailability in the gastrointestinal tract.One of the critical and most overlooked factors is the symbiotic gut microbiota that can modulate the bioavailability of oral drugs by participating in the biotransformation of oral drugs,influencing the drug transport process and altering some gastrointestinal properties.In this review,we summarized the existing research investigating the possible relationship between the gut microbiota and the bioavailability of oral drugs,which may provide great ideas and useful instructions for the design of novel drug delivery systems or the achievement of personalized medicine.展开更多
Objective To deliver multiple component drugs to colon site and sustain a synchronous release for better therapeutic effect. For achieving this purpose, colon specific pellet containing total alkaloids of Sophora alop...Objective To deliver multiple component drugs to colon site and sustain a synchronous release for better therapeutic effect. For achieving this purpose, colon specific pellet containing total alkaloids of Sophora alopecuroides （TASA） was prepared. Methods The pellet was prepared by extrasion-spheronizing and subsequently coated with three layers of two polymers. Results The pellet core consisted of 40% TASA, 1：2 in ratio of Bletilla striata polysaccharide （BSP）, an enzyme-degradable material, to microcrystalline cellu{ose （MCC）, filler, and 1% CMC-Na solution as binder by optimization. Concerning of the three coated layers, the outer layer was coated with Eudragit RS30D for controlling drug release in colon, the intermediate layer and the inner layer were coated with same polymer, Eudragit $100, for preventing drug release in upper gastrointestinal tract, which required 23.2%, 21.7%, and 9.3% weigh gain, respectively. The coated pellets released 1.20% of sophoridine and 1.98% of matrine in media mimicking the stomach condition for 2 h, and 23.88% of sophoridine and 22.91% of matrine in media mimicking the intestine for 3 h and finally 90.25% of sophoridine and 89.94% of matrine in colonic conditions within 24 h, And the similarity factor f2 of sophoridine and matrine of release curve for investigated formulation was internal in （50-100） and 〉 80, demonstrating that sophoridine and matrine in formulation achieved a synchronous release. Conclusion The coated pellets achieve a certain colon-specific release and synchronous release.展开更多
文摘Despite the advent of biological products, such as anti-tumor necrosis factor-α monoclonal antibodies (infliximab and adalimumab), for treatment of moderate to severe cases of inflammatory bowel disease (IBD), most patients depend upon aminosalicylates as the conventional treatment option. In recent years, the increased knowledge of complex pathophysiological processes underlying IBD has resulted in development of a number of newer pharmaceutical agents like low-molecular-weight heparin, omega-3 fatty acids, probiotics and innovative formulations such as high-dose, once-daily multi-matrix mesalamine, which are designed to minimize the inflammatory process through inhibition of different targets. Optimization of delivery of existing drugs to the colon using the prodrug approach is another attractive alternative that has been utilized and commercialized for 5-aminosalicylic acid (ASA) in the form of sulfasalazine, balsalazide, olsalazine and ipsalazine, but rarely for its positional isomer 4-ASA - a well-established antitubercular drug that is twice as potent as 5-ASA against IBD, and more specifically, ulcerative colitis. The present review focuses on the complete profile of 4-ASA and its advantages over 5-ASA and colon-targeting prodrugs reported so far for the management of IBD. The review also emphasizes the need for reappraisal of this promising but unexplored entity as a potential treatment option for IBD.
文摘A series of cross-linked gels of Poly（N-isopropylacrylamide） [P（NIPAAm）] and Poly（methacr-ylic acid）[P（MAA）] homopolymers and P（NIPAAm-co-MAA） random copolymers were synthesized based on NIPAAm and MAA using 4,4-Bis-（methacryloylamino） azobenzene （BMAAB） as a cross-linker. The swelling behavior of these hydrogels in different pH buffer solutions was studied. The influential factors of the gels including composition of NIPAAm and MAA, pH and temperature upon swelling behavior were investigated. The obtained gels not only hold pH and thermometrical sensitivity, but also take on enzymatic sensitivity due to the cross-linker could be degraded by enzymes of colon. Swelling equilibrium degree of copolymers was very low in acidic medium, which could avoid drug releasing due to biggish swelling of carder in stomach. Hydrogels would partly swell owing to higher pH value in small intestine. When arrived in colon, hydrogels completely swelled, meanwhile, azoenzymes located would degrade azo-bonds of polymeric network and then drug released in colon.
文摘AIM： To investigate the release of cyclodextrin-S-amino- salicylic acid （CyD-S-ASA） in cecum and colon. METHODS： An anti-inflammatory drug 5-ASA was conjugated onto the hydroxyl groups of α-, β- and γ-cydodextrins （CyDs） through an ester linkage, and the in vivo drug release behavior of these prodrugs in rat＇ s gastrointestinal tract after the oral administration was investigated. RESULTS： The 5-ASA concentration in the rat＇s stomach and small intestine after the oral administration of CyD- 5-ASA conjugate was much lower than that after the oral administration of 5-ASA alone. The lower concentration was attributable to the passage of the conjugate through the stomach and small intestine without significant degradation or absorption, followed by the degradation of the conjugate site-specific in the cecum and colon. The oral administration of CyD-S-ASA resulted in lower plasma and urine concentration of 5-ASA than that of 5-ASA alone. CONCLUSION： CyD-5-ASA conjugates may be used as prodrugs for colon-specific drug delivery system.
基金Funded by the National Natural Science Foundation of China (No.50503019)
文摘A series of cross-linked hydrogels for colon-specific drug delivery were synthesized by graft copolymerization of Chitosan and acrylic acid using N, N＇-methylene-bis-（acrylamide） as a cross-linker. Their swelling behavior in different pH buffer solutions and colonic enzymatic degradability were studied. The obtained results show that these hydrogels have good pH sensitivity which can avoid drug release in stomach, and their swelling kinetics in stimulant intestinal environment follow second-order swelling kinetics equation. The factors influencing the swelling kinetics include the degree of cross-linking and the composition, which may control no release or a little amount release of drug inside the hydrogels in the small intestine by tailoring these factors. The gels are degradable by colonic enzymes and there is a correlativity between the degradation of networks and the swelling degree of the gels, which may trigger the release of drug in the colon. The hydrogels show a great potential for their application in oral colon-specific drug delivery system.
基金National Natural Science Foundation of China(Nos.82171333,82272847,82202318)Postdoctoral Fellowship Program of CPSF(GZB20230675,China)+2 种基金The Henan Province Fund for Cultivating Advantageous Disciplines(No.222301420012,China)Central Plains Science and Technology Innovation Leading Talent Project(No.234200510005,China)Graduate Education Reform Project of Henan Province(2023SJGLX127Y,China).
文摘A colon-specific drug delivery system has great potential for the oral administration of colorectal cancer.However,the uncontrollable in vivo fate of liposomes makes their effectiveness for colonic location,and intratumoral accumulation remains unsatisfactory.Here,an oral colon-specific drug delivery system(CBS-CS@Lipo/Oxp/MTZ)was constructed by covalently conjugating Clostridium butyricum spores(CBS)with drugs loaded chitosan(CS)-coated liposomes,where the model chemotherapy drug oxaliplatin(Oxp)and anti-anaerobic bacteria agent metronidazole(MTZ)were loaded.Following oral administration,CBS germinated into Clostridium butyricum(CB)and colonized in the colon.Combined with colonic specificallyβ-glucosidase responsive degrading of CS,dual colon-specific release of liposomes was achieved.And the accumulation of liposomes at the CRC site furtherly increased by 2.68-fold.Simultaneously,the released liposomes penetrated deep tumor tissue via the permeation enhancement effect of CS to kill localized intratumoral bacteria.Collaborating with blocking the translocation of intestinal pathogenic bacteria from lumen to tumor with the gut microbiota modulation of CB,the intratumoral pathogenic bacteria were eliminated fundamentally,blocking their recruitment to immunosuppressive cells.Furtherly,synchronized with lipopolysaccharide(LPS)released from MTZ-induced dead Fusobacterium nucleatum and the tumor-associated antigens produced by Oxp-caused immunogenic dead cells,they jointly enhanced tumor infiltration of CD8^(+)T cells and reactivated robust antitumor immunity.
基金This work was financially supported by the ShenBoTai Biological Technology Co.,LTD(Shenzhen,China).
文摘Pectin-chitosan complex was prepared as a candidate material for colon-specific capsule.First,the effects of beating on the properties of complex films were explored.Fourier transform infrared(FT-IR)spectroscopy was used to analyze the reaction mechanics,and an in vitro simulation experiment was performed to determine the degradation performance.Second,the capsule was prepared using pectin-chitosan complex as the main raw material;its targeting effect was evaluated and analyzed.Results indicated that the film became smooth and compact by beating.FT-IR data indicated that cross-linking occurred between the hydroxyl group of pectin and the amino group of chitosan to form a network structure.In vitro experiment showed that the pectin-chitosan complex film could not be degraded in the simulated gastric and intestinal fluids.However,pectin-chitosan complex could be degraded in the simulated colonic fluid,so it could be a potential candidate for colon-specific capsule.Because the complex has no ability for forming hard capsule,the carrageenan and starch were added to increase the flexibility,gelation,transparency and mechanical properties of the film.The preferred composition suitable for preparing the capsule was a mass ratio(2:1:1)of pectin-chitosan/carrageenan/starch mixture.The capsule showed excellent features in terms of shape,water content,and brittleness.The drug release rate reached 93.33%in colonic fluid for 1 h when bovine serum albumin was the model drug.Therefore,pectin-chitosan may be considered as a new material for colon-targeted capsule.
基金financially supported by Beijing Nova Program(Nos.Z211100002121127 and 20220484219)Beijing Natural Science Foundation(No.L212059)+1 种基金Fundamental Research Funds for the Central Universities(No.3332021101)CAMS Innovation Fund for Medical Sciences(CIFMS,Nos.2021-I2M-1-026 and 2021-I2M-1-028).
文摘Ulcerative colitis(UC)is a common progressive inflammatory disease whose incidence has increased rapidly in recent years,and can develop into colorectal cancer in severe cases.There are currently no adequate or effective treatments for UC due to the fact that some patients have found suboptimal results after repeated administration,while others have experienced adverse effects.With the rapid development of nanotechnology,developing innovative colon-targeting platforms is essential to improving efficacy,reducing side effects,and improving patient compliance.In this review,we summarize the pathophysiological characteristics of UC and the most recent status of numerous nanodrug delivery systems based on different targeting mechanisms in treating UC.Oral,intravenous,and rectal drug delivery nanoparticles targeting the colon are discussed,which can provide ideas for the design of colon-targeting nanoparticles for the treatment of colon diseases,especially for the treatment of UC.Last but not least,we provide a glimpse into the future of colon-targeted delivery systems,as well as future advancements in the field.
基金Research Funding of Medical Association of Japanese-Chinese, Japan
文摘AIM: To investigate the permeability characteristics of rebamipide across intestinal mucosa, and examine the effects of some absorption enhancers on the permeability across the colonic tissue. Another purpose is to demonstrate the colon-specific delivery of rebamipide with or without absorption enhancers using chitosan capsule as a carrier. METHODS: The permeability of rebamipide was evaluated using an in vitro diffusion chamber system, and the effects of some absorption enhancers on the permeability via colon were further investigated. The release of rebamipide from chitosan or gelatin capsule was studied by Japan Pharmacopoeia rotating basket method. The colonic and plasma concentrations were analyzed by high performance liquid chromatography (HPLC) to evaluate colon-targeting action after oral administration of various dosage forms, and rebamipide with absorption enhancers in chitosan dosage forms. RESULTS: The permeability of rebamipide across the jejunal or ileal membranes was higher than the colonic membranes. Both sodium laurate (C12) and labrasol signifi cantly increased permeability across the colon membranes. On the other hand, the release of rebamipide from chitosan capsule was less than 10%totally within 6 h. The area under concentration-time profile of drug in the colon mucosa using chitosan capsules (AUCLI, 1 6011.2 ng·h/g) was 2.5 times and 4.4 times greater than using gelatin capsules and CMC suspension, respectively. Meanwhile, the area under concentration-time profile of drug in the plasma (AUCPL) was 1016.0 ng·h/mL for chitosan capsule, 1887.9 ng·h/mL for CMC suspension p and 2163.5 ng·h/mL for gelatin capsule. Overall, both AUCLI and AUCPL were increased when C12 was co-administrated, but the increase of AUCLI was much greater; the drug delivery index (DDI) was more than 1 compared with simple chitosan capsule group. CONCLUSION: There was a regional difference in the permeability of Rabamipide across the jejunum, ileum and the colon, and passive diffusion seems to be one of the major transport mechanisms of rebamipide. Absorption enhancers can increase the permeability of rebamipide across the colon tissue signifi cantly. In addition, chitosan capsule may be a useful carrier to deliver rebamipide to the colon specifi cally and the co-administration of C12 with rebamipide may also be very useful in local treatment.
文摘The aim of this study was to evaluate the effect of coating of alginate-chitosan (AL:CS) beads on the colonic drug delivery. The AL:CS systems containing triamcinolone (TC) were coated with the HPMCP and Eudragit? L100 by immersion and by spraying methods. The drug release profile in simulated colonic medium was determined using 5% human fecal content suspension in 0.01 N buffer solution, pH 6.8. The systems coated with HPMCP showed a lower rate of drug delivery in simulated enteric medium. The delivery profile in simulated colonic medium followed zero-order kinetic. The coated systems provided a promising drug-delivery profile for application in colonic drug delivery.
基金supported by Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2017-I2M1e011,China)the Drug Innovation Major Project(2018ZX09711001-002-005,China)+1 种基金National Natural Science Foundation of China(No.82073778,China)the Fundamental Research Funds for the Central Public Welfare Research Institutes(2018PT35002,China)
文摘Due to its safety,convenience,low cost and good compliance,oral administration attracts lots of attention.However,the efficacy of many oral drugs is limited to their unsatisfactory bioavailability in the gastrointestinal tract.One of the critical and most overlooked factors is the symbiotic gut microbiota that can modulate the bioavailability of oral drugs by participating in the biotransformation of oral drugs,influencing the drug transport process and altering some gastrointestinal properties.In this review,we summarized the existing research investigating the possible relationship between the gut microbiota and the bioavailability of oral drugs,which may provide great ideas and useful instructions for the design of novel drug delivery systems or the achievement of personalized medicine.
基金Major science and technology projects of Guangdong province,China(2013A022100039)Science innovation projects of higher school(2012KJCX0060)+3 种基金Technology Bureau of ZhanjiangGuangdong province,China(2011C3108015)Guangdong province sail plan project of high level talents in 2014the National Natural Science Foundation of China(81473401)
文摘Objective To deliver multiple component drugs to colon site and sustain a synchronous release for better therapeutic effect. For achieving this purpose, colon specific pellet containing total alkaloids of Sophora alopecuroides （TASA） was prepared. Methods The pellet was prepared by extrasion-spheronizing and subsequently coated with three layers of two polymers. Results The pellet core consisted of 40% TASA, 1：2 in ratio of Bletilla striata polysaccharide （BSP）, an enzyme-degradable material, to microcrystalline cellu{ose （MCC）, filler, and 1% CMC-Na solution as binder by optimization. Concerning of the three coated layers, the outer layer was coated with Eudragit RS30D for controlling drug release in colon, the intermediate layer and the inner layer were coated with same polymer, Eudragit $100, for preventing drug release in upper gastrointestinal tract, which required 23.2%, 21.7%, and 9.3% weigh gain, respectively. The coated pellets released 1.20% of sophoridine and 1.98% of matrine in media mimicking the stomach condition for 2 h, and 23.88% of sophoridine and 22.91% of matrine in media mimicking the intestine for 3 h and finally 90.25% of sophoridine and 89.94% of matrine in colonic conditions within 24 h, And the similarity factor f2 of sophoridine and matrine of release curve for investigated formulation was internal in （50-100） and 〉 80, demonstrating that sophoridine and matrine in formulation achieved a synchronous release. Conclusion The coated pellets achieve a certain colon-specific release and synchronous release.
