title: pH-dependent release of platycodin mitigates its gastrointestinal mucosa irritation after oral administration in rats.
abstract: The present study aimed to evaluate the gastrointestinal mucosa irritation of three platycodin formulations. Platycodin-loaded core pellets were prepared via extrusion-spheronization method and coated with Eudragit(®) L100-55 (L100) or Eudragit(®) S100 (S100) for pH-dependent release. The release of platycodin D from coated pellets exhibited pH dependent release profiles. The pharmacokinetic study in rats showed that Tmax of the coated pellets were prolonged as compared to that of un-coated pellets. The S100-coated pellets possess a lower Cmax and decreased AUC0-24h as compared to the L100-coated and uncoated pellets. Hematoxylin-eosin staining and nuclear factor Kappa B (NF-κB) measurement were carried out to observe the gastrointestinal mucosa irritations. The results revealed that the irritations of platycodin on the upper gastrointestinal mucosa are dose-dependent. However, no obvious irritation effect on the gastrointestinal tissues of rats was detected after oral administration of the coated pellets. In addition, the amount of NF-κB in the stomach of rats treated with the uncoated pellets was about fivefold higher as compared to that of the coated pellets. In summary, the L100-coated platycodin pellets exhibited higher oral bioavailability and less gastrointestinal mucosa irritations as compared to the other two formulations.
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, College of Pharmaceutical Science, Soochow University, Suzhou, 215123, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, College of Pharmaceutical Science, Soochow University, Suzhou, 215123, China.
authors.forename: Wen-Wen
authors.initials: WW
authors.lastname: Yang
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, College of Pharmaceutical Science, Soochow University, Suzhou, 215123, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Shen
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, College of Pharmaceutical Science, Soochow University, Suzhou, 215123, China.
authors.forename: Qing-Ri
authors.initials: QR
authors.lastname: Cao
authors.affiliation: Bioavailability Control Laboratory, College of Pharmacy, Ajou University, Suwon, 443-749, Korea.
authors.forename: Beom-Jin
authors.initials: BJ
authors.lastname: Lee
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, College of Pharmaceutical Science, Soochow University, Suzhou, 215123, China. jhcui@suda.edu.cn.
authors.forename: Jing-Hao
authors.initials: JH
authors.lastname: Cui
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D011109:Polymethacrylic Acids / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry* / Q000633:toxicity; D013499:Surface Properties
chemical_list: D000180:Acrylic Resins; D003692:Delayed-Action Preparations; C446821:Eudragit L100-55; D016328:NF-kappa B; D011109:Polymethacrylic Acids; D012503:Saponins; C008936:platycodin; C038300:methylmethacrylate-methacrylic acid copolymer
keywords: Gastrointestinal mucosa; Irritation; PH dependent release; Pharmacokinetics; Platycodin D