Improvement of side-effects and treatment on the experimental colitis in mice of a resin microcapsule-loading hydrocortisone sodium succinate

• Published in: Drug development and industrial pharmacy Vol. 43; no. 3; pp. 448 - 457
• Main Authors: Dong, Kai, Zhang, Hefeng, Yan, Yan, Sun, Jinyao, Dong, Yalin, Wang, Ke, Zhang, Lu, Shi, Xianpeng, Xing, Jianfeng
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 04-03-2017
• Subjects: amberlite 717; Animals; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - pharmacokinetics; Capsules; Colitis - drug therapy; Colitis - metabolism; colon targeting; eudragit S100; Hydrocortisone - administration & dosage; Hydrocortisone - analogs & derivatives; Hydrocortisone - pharmacokinetics; hydrocortisone sodium succinate; Mice; Microspheres; Polymethacrylic Acids - administration & dosage; Polymethacrylic Acids - pharmacokinetics; Random Allocation; Rats; Resins, Synthetic - administration & dosage; Resins, Synthetic - pharmacokinetics; side-effects; Treatment Outcome; Ulcerative colitis; hydrocortisone sodium succinate; amberlite 717; colon targeting; eudragit S100; side-effects; Ulcerative colitis
• ISSN: 0363-9045; 1520-5762
• DOI: 10.1080/03639045.2016.1258410

Context: Extensive or long-time use of corticosteroids often causes many toxic side-effects. The ion exchange resins and the coating material, Eudragit, can be used in combination to form a new oral delivery system to deliver corticosteroids.
Objectives: The resin microcapsule (DRM) composed by Amberlite 717 and Eudragit S100 was used to target hydrocortisone (HC) to the colon in order to improve its treatment effect on ulcerative colitis (UC) and reduce its toxic side-effects.
Methods: Hydrocortisone sodium succinate (HSS) was sequentially encapsulated in Amberlite 717 and Eudragit S100 to prepare the HSS-loaded resin microcapsule (HSS-DRM). The scanning electron microscopy (SEM) was employed to investigate the morphology and structure of HSS-DRM. The in vitro release and in vivo studies of pharmacokinetics and intestinal drug residues in rat were used to study the colon-targeting of HSS-DRM. The mouse induced by 2,4,6-trinitrobenzenesulfonic acid was used to study the treatment of HSS-DRM on experimental colitis.
Results: SEM study showed good morphology and structure of HSS-DRM. In the in vitro release study, > 80% of HSS was released in the colon environment (pH 7.4). The in vivo studies showed good colon-targeting of HSS-DRM (T
max 
= 0.97 h, C
max 
= 118.28 µg/mL of HSS; T
max
 = 2.16 h, C
max
 = 64.47 µg/mL of HSS-DRM). Moreover, the HSS-DRM could reduce adverse reactions induced by HSS and had good therapeutic effects on the experimental colitis.
Conclusions: The resin microcapsule system has good colon-targeting and can be used in the development of colon-targeting preparations.