Inflammatory bowel diseases(IBD)significantly contribute to high mortality globally and negatively affect patients’qualifications of life.The gastrointestinal tract has unique anatomical characteristics and physiolog...Inflammatory bowel diseases(IBD)significantly contribute to high mortality globally and negatively affect patients’qualifications of life.The gastrointestinal tract has unique anatomical characteristics and physiological environment limitations.Moreover,certain natural or synthetic anti-inflammatory drugs are associated with poor targeting,low drug accumulation at the lesion site,and other side effects,hindering them from exerting their therapeutic effects.Colon-targeted drug delivery systems represent attractive alternatives as novel carriers for IBD treatment.This review mainly discusses the treatment status of IBD,obstacles to drug delivery,design strategies of colon-targeted delivery systems,and perspectives on the existing complementary therapies.Moreover,based on recent reports,we summarized the therapeutic mechanism of colon-targeted drug delivery.Finally,we addressed the challenges and future directions to facilitate the exploitation of advanced nanomedicine for IBD therapy.展开更多
Drug-loaded micelles for oral administration are desired for its conve nience,low cost and flexibility,but current designs rely on introducing pH responsiveness,leaving problems like drug leakage and low accuracy of t...Drug-loaded micelles for oral administration are desired for its conve nience,low cost and flexibility,but current designs rely on introducing pH responsiveness,leaving problems like drug leakage and low accuracy of targeted delivery un-solved.Herein,we reported an acid-resistant ROS-responsive hyperbranched polythioether which can self-assemble into micellar structure and pass through the gastrointestinal tract without leaking drugs.At the inflammatory lesions,the thioester bonds are oxidized to sulphone groups to significantly increase the hydrophilicity in response to accumulated ROS species and efficiently release the encapsulated drugs.Animal experiments,including the evaluation of bodyweight,colon length,MPO activity,spleen index,histology and quantitative reverse transcription PCR,evidenced that the drug-loaded micelles have improved therapeutic efficiency compared to bare drug administration for the treatment of DSS-induced colitis in mice.This study provides an example of oral administrated micellar system can be extended for the treatment of other intestinal tract diseases.展开更多
To develop a colon-targeting bioreversible delivery system for β-boswellic acid (BBA) and explore utility of its prodrugs in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats.METHODSSynthesis of 4 co...To develop a colon-targeting bioreversible delivery system for β-boswellic acid (BBA) and explore utility of its prodrugs in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats.METHODSSynthesis of 4 co-drugs of BBA with essential amino acids was achieved by CDI coupling, followed by their spectral characterization. In vitro kinetics were studied by HPLC in aqueous buffers, homogenates of gastrointestinal tract and fecal matter. In vivo kinetic studies were performed in Wistar rat plasma, urine and feces. The prodrugs were screened in TNBS-induced colitis modeled Wistar rats. Statistical significance was assumed at P < 0.05, P < 0.01, P < 0.001 when compared with disease controls using one-way and two-way ANOVAs.RESULTSProdrugs were stable in 0.05 mol/L HCl buffer (pH 1.2) and stomach homogenates. Negligible hydrolysis was observed in phosphate buffer and intestinal homogenates. Substantial release (55%-72% and 68%-86%) of BBA was achieved in rat fecal matter and homogenates of colon. In vivo studies of BBA with L-tryptophan (BT) authenticated colon-specific release of BBA. But, surprisingly substantial concentration of BBA was seen to reach the systemic circulation due to probable absorption through colonic mucosa. Site-specifically enhanced bioavailability of BBA could be achieved in colon, which resulted in demonstration of significant mitigating effect on TNBS-induced colitis in rats without inducing any adverse effects on stomach, liver and pancreas. Prodrug of BT was found to be 1.7% (P < 0.001) superior than sulfasalazine in reducing the inflammation to colon among all prodrugs tested.CONCLUSIONThe outcome of this study strongly suggests that these prodrugs might have dual applicability to inflammatory bowel disease and chronotherapy of rheumatoid arthritis.展开更多
Atopic dermatitis(AD)is a prevalent cutaneous condition with chronic inflammation and immune dysregulation,posing a public health concern owing to its long-lasting and recurrent nature.Butyrate,a short-chain fatty aci...Atopic dermatitis(AD)is a prevalent cutaneous condition with chronic inflammation and immune dysregulation,posing a public health concern owing to its long-lasting and recurrent nature.Butyrate,a short-chain fatty acid produced by gut microbiota,exhibits significant anti-inflammatory effects in AD.Yet,its delivery via butyrylated starch for prolonged release in the colon has not been adequately investigated.In this study,butyrylated Smilax glabra starch(BSGS)was synthesized and its therapeutic potential against AD via modulation of the gut–skin axis was examined.BSGS exhibited a C-type crystalline structure and highly resistance to gastrointestinal digestion.In vitro anaerobic fermentation showed that BSGS effectively promoted the generation of short-chain fatty acids,especially butyrate,and positively influenced the gut microbial composition.In AD mice,BSGS administration considerably mitigated cutaneous inflammation,lowered serum proinflammatory cytokines,restored intestinal barrier integrity,and modulated gut microbiota by increasing Bacteroides and norank_f__Prevotellaceae while decreasing Alistipes and norank_o__RF39.This therapeutic effect was associated with butyrate release and NF-κB pathway suppression,as evidenced by the reduced phosphorylation of p65 and IκBα.These findings establish that BSGS,a novel colon-targeted butyrate donor,holds promising potential in AD treatment by modulating the immune system via the gut–skin axis.展开更多
Baicalin(BA)is a flavonoid extracted from the dried root of Scutellaria baicalensis Georgi with excellent antioxidant and anti-inflammatory biological activities.In this study,Eudragit S100 was used as the colonic tar...Baicalin(BA)is a flavonoid extracted from the dried root of Scutellaria baicalensis Georgi with excellent antioxidant and anti-inflammatory biological activities.In this study,Eudragit S100 was used as the colonic target material to prepare BA colonic targeting granules(EBCGs)based on plasticizer dry powder coating technology to improve the targeting transportation performance of BA.In vitro studies showed that EBCGs with pH-sensitive properties were successfully prepared by plasticizer dry powder coating,and in vivo animal imaging studies showed that EBCGs could deliver BA to the colon and inhibit the release of BA in the upper gastrointestinal tract(GIT).In vivo studies showed that EBCGs had good therapeutic effects in colitis,which reduced expression levels of tumor necrosis factor alpha(TNF-α)and interleukin-1β(IL-1β)and increased superoxide dismutase(SOD)activities in the colonic tissues of rats with colitis.In conclusion,Eudragit S100 could be used for the preparation of multi-unit oral colon-targeted formulations by plasticizer dry powder coating technology,and our prepared EBCGs had good colon-targeting properties,which could improve the therapeutic effect and provide a potential application for ulcerative colitis(UC).展开更多
基金supported by CACMS Innovation Fund(CI2021B016,CI2021A04801)National Natural Science Foundation of China(82192913,82174073)+2 种基金Qihuang Scholar ProgramCACMS Foundation(ZZ13-035-10)China Postdoctoral Science Foundation(2023M733913).
文摘Inflammatory bowel diseases(IBD)significantly contribute to high mortality globally and negatively affect patients’qualifications of life.The gastrointestinal tract has unique anatomical characteristics and physiological environment limitations.Moreover,certain natural or synthetic anti-inflammatory drugs are associated with poor targeting,low drug accumulation at the lesion site,and other side effects,hindering them from exerting their therapeutic effects.Colon-targeted drug delivery systems represent attractive alternatives as novel carriers for IBD treatment.This review mainly discusses the treatment status of IBD,obstacles to drug delivery,design strategies of colon-targeted delivery systems,and perspectives on the existing complementary therapies.Moreover,based on recent reports,we summarized the therapeutic mechanism of colon-targeted drug delivery.Finally,we addressed the challenges and future directions to facilitate the exploitation of advanced nanomedicine for IBD therapy.
基金the National Nature Science Foundation of China(NSFC,Nos.51803115,21636006,81773686)Nature Science Foundation of Shaanxi Province(No.2019JQ-528)+2 种基金the Fundamental Research Funds for the Central Universities(Nos.GK201801003,GK201802009,GK201901001)Young Talent Fund of University Association for Science and Technology in Shaanxi,China(No.20180602)the Program of Introducing Talents of Discipline to Universities(No.B14041)。
文摘Drug-loaded micelles for oral administration are desired for its conve nience,low cost and flexibility,but current designs rely on introducing pH responsiveness,leaving problems like drug leakage and low accuracy of targeted delivery un-solved.Herein,we reported an acid-resistant ROS-responsive hyperbranched polythioether which can self-assemble into micellar structure and pass through the gastrointestinal tract without leaking drugs.At the inflammatory lesions,the thioester bonds are oxidized to sulphone groups to significantly increase the hydrophilicity in response to accumulated ROS species and efficiently release the encapsulated drugs.Animal experiments,including the evaluation of bodyweight,colon length,MPO activity,spleen index,histology and quantitative reverse transcription PCR,evidenced that the drug-loaded micelles have improved therapeutic efficiency compared to bare drug administration for the treatment of DSS-induced colitis in mice.This study provides an example of oral administrated micellar system can be extended for the treatment of other intestinal tract diseases.
文摘To develop a colon-targeting bioreversible delivery system for β-boswellic acid (BBA) and explore utility of its prodrugs in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats.METHODSSynthesis of 4 co-drugs of BBA with essential amino acids was achieved by CDI coupling, followed by their spectral characterization. In vitro kinetics were studied by HPLC in aqueous buffers, homogenates of gastrointestinal tract and fecal matter. In vivo kinetic studies were performed in Wistar rat plasma, urine and feces. The prodrugs were screened in TNBS-induced colitis modeled Wistar rats. Statistical significance was assumed at P < 0.05, P < 0.01, P < 0.001 when compared with disease controls using one-way and two-way ANOVAs.RESULTSProdrugs were stable in 0.05 mol/L HCl buffer (pH 1.2) and stomach homogenates. Negligible hydrolysis was observed in phosphate buffer and intestinal homogenates. Substantial release (55%-72% and 68%-86%) of BBA was achieved in rat fecal matter and homogenates of colon. In vivo studies of BBA with L-tryptophan (BT) authenticated colon-specific release of BBA. But, surprisingly substantial concentration of BBA was seen to reach the systemic circulation due to probable absorption through colonic mucosa. Site-specifically enhanced bioavailability of BBA could be achieved in colon, which resulted in demonstration of significant mitigating effect on TNBS-induced colitis in rats without inducing any adverse effects on stomach, liver and pancreas. Prodrug of BT was found to be 1.7% (P < 0.001) superior than sulfasalazine in reducing the inflammation to colon among all prodrugs tested.CONCLUSIONThe outcome of this study strongly suggests that these prodrugs might have dual applicability to inflammatory bowel disease and chronotherapy of rheumatoid arthritis.
基金supported by the National Natural Science Foundation of China(Grant No.82174074).
文摘Atopic dermatitis(AD)is a prevalent cutaneous condition with chronic inflammation and immune dysregulation,posing a public health concern owing to its long-lasting and recurrent nature.Butyrate,a short-chain fatty acid produced by gut microbiota,exhibits significant anti-inflammatory effects in AD.Yet,its delivery via butyrylated starch for prolonged release in the colon has not been adequately investigated.In this study,butyrylated Smilax glabra starch(BSGS)was synthesized and its therapeutic potential against AD via modulation of the gut–skin axis was examined.BSGS exhibited a C-type crystalline structure and highly resistance to gastrointestinal digestion.In vitro anaerobic fermentation showed that BSGS effectively promoted the generation of short-chain fatty acids,especially butyrate,and positively influenced the gut microbial composition.In AD mice,BSGS administration considerably mitigated cutaneous inflammation,lowered serum proinflammatory cytokines,restored intestinal barrier integrity,and modulated gut microbiota by increasing Bacteroides and norank_f__Prevotellaceae while decreasing Alistipes and norank_o__RF39.This therapeutic effect was associated with butyrate release and NF-κB pathway suppression,as evidenced by the reduced phosphorylation of p65 and IκBα.These findings establish that BSGS,a novel colon-targeted butyrate donor,holds promising potential in AD treatment by modulating the immune system via the gut–skin axis.
基金supported by Outstanding Youth Foundation of Jiangxi Province(grant No.20224ACB216019)Natural Science Foundation of Jiangxi Province(grant Nos.20202BABL206151 and 20202BABL216026)+2 种基金Doctoral startup fund of Jiangxi Science and Technology Normal University(grant No.2019BSQD015)Department Education Science and Technology Research Project of Jiangxi(grant No.GJ201134)the Open Project of Jiangxi Provincial Key Laboratory of Drug Design and Evaluation(grant No.JKD-KF-2104).
文摘Baicalin(BA)is a flavonoid extracted from the dried root of Scutellaria baicalensis Georgi with excellent antioxidant and anti-inflammatory biological activities.In this study,Eudragit S100 was used as the colonic target material to prepare BA colonic targeting granules(EBCGs)based on plasticizer dry powder coating technology to improve the targeting transportation performance of BA.In vitro studies showed that EBCGs with pH-sensitive properties were successfully prepared by plasticizer dry powder coating,and in vivo animal imaging studies showed that EBCGs could deliver BA to the colon and inhibit the release of BA in the upper gastrointestinal tract(GIT).In vivo studies showed that EBCGs had good therapeutic effects in colitis,which reduced expression levels of tumor necrosis factor alpha(TNF-α)and interleukin-1β(IL-1β)and increased superoxide dismutase(SOD)activities in the colonic tissues of rats with colitis.In conclusion,Eudragit S100 could be used for the preparation of multi-unit oral colon-targeted formulations by plasticizer dry powder coating technology,and our prepared EBCGs had good colon-targeting properties,which could improve the therapeutic effect and provide a potential application for ulcerative colitis(UC).
