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
Both electrospinning apparatus and their commercial products are extending their applications in a wide variety of fields.However,very limited reports can be found about how to implement an energy-saving process and i...Both electrospinning apparatus and their commercial products are extending their applications in a wide variety of fields.However,very limited reports can be found about how to implement an energy-saving process and in turn to reduce the production cost.In this paper,a brand-new type of coaxial spinneret with a solid core and its electrospinning methods are developed.A novel sort of medicated Eudragit/lipid hybrid nanofibers are generated for providing a colon-targeted sustained release of aspirin.A series of characterizations demonstrates that the as-prepared hybrid nanofibers have a fine linear morphology with the aspirin/lipid separated from the matrix Eudragit to form many tiny islands.In vitro dissolution tests exhibit that the hybrid nanofibers are able to effectively prevent the release of aspirin under an acid condition(8.7%±3.4%for the first two hours),whereas prolong the drug release time period under a neutral condition(99.7±4.2%at the seventh hour).The energy-saving mechanism is discussed in detail.The prepared aspirin-loaded hybrid nanofibers can be further transferred into an oral dosage form for potential application in countering COVID-19 in the future.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
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
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).
基金This study was supported by the Natural Science Foundation of Shanghai,China(No.20ZR1439000)the USST college student innovation projects,China(Nos.SH2020227&XJ2020376-2020378).
文摘Both electrospinning apparatus and their commercial products are extending their applications in a wide variety of fields.However,very limited reports can be found about how to implement an energy-saving process and in turn to reduce the production cost.In this paper,a brand-new type of coaxial spinneret with a solid core and its electrospinning methods are developed.A novel sort of medicated Eudragit/lipid hybrid nanofibers are generated for providing a colon-targeted sustained release of aspirin.A series of characterizations demonstrates that the as-prepared hybrid nanofibers have a fine linear morphology with the aspirin/lipid separated from the matrix Eudragit to form many tiny islands.In vitro dissolution tests exhibit that the hybrid nanofibers are able to effectively prevent the release of aspirin under an acid condition(8.7%±3.4%for the first two hours),whereas prolong the drug release time period under a neutral condition(99.7±4.2%at the seventh hour).The energy-saving mechanism is discussed in detail.The prepared aspirin-loaded hybrid nanofibers can be further transferred into an oral dosage form for potential application in countering COVID-19 in the future.
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.
