title: A novel microsphere with a three-layer structure for duodenum-specific drug delivery.
abstract: Owing to the quick elimination of drug from duodenum and the depth of Helicobacter pylori (H. pylori) colonized in mucus, antibiotic therapy often fails in the eradication of H. pylori infection for duodenal ulcer. A novel duodenum-specific microsphere (DSM) consisting of three-layer structure was developed to enhance the drug concentration and retention time in duodenal mucus layer. Firstly a core-shell mucoadhesive microsphere was prepared with a novel emulsification/coagulation coating method by introducing drug loaded Eudragit cores into a thiolated chitosan mucoadhesive layer. Then the obtained core-shell mucoadhesive microspheres were further coated with hydroxypropyl methylcellulose acetate maleate as the pH-sensitive layer for the trigger of mucoadhesion and drug release in duodenum. From the fluorescence microscopic and scanning electron microscopic images, the three-layer structure was successfully established. The microspheres exhibited a duodenum-specific trigger performance, good mucoadhesive property and pH-dependent drug release. In vivo study performed in rats demonstrated that DSM exhibited about 3-fold augmentation of AUC and about 5-fold augmentation of C(max) for duodenal mucus drug concentration compared with free drug suspension. These results suggest that the three-layer structure microspheres may provide a promising approach for duodenum-targeting drug delivery system.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, Sichuan, PR China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhu
authors.forename: Dan
authors.initials: D
authors.lastname: Zhou
authors.forename: Yun
authors.initials: Y
authors.lastname: Jin
authors.forename: Yu-pin
authors.initials: YP
authors.lastname: Song
authors.forename: Zhi-rong
authors.initials: ZR
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D001599:Berberine / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D048271:Chitosan / Q000737:chemistry; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods*; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D005079:Excipients / Q000737:chemistry; D008863:Microspheres; D009077:Mucins / Q000737:chemistry; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties; D013552:Swine
chemical_list: D000900:Anti-Bacterial Agents; D005079:Excipients; D009077:Mucins; D011108:Polymers; D001599:Berberine; D048271:Chitosan