title: A simple and inexpensive enteric-coated capsule for delivery of acid-labile macromolecules to the small intestine.
abstract: Understanding the ecology of the gastrointestinal tract and the impact of the contents on the host mucosa is emerging as an important area for defining both wellness and susceptibility to disease. Targeted delivery of drugs to treat specific small intestinal disorders such as small bowel bacterial overgrowth and targeting molecules to interrogate or to deliver vaccines to the remote regions of the small intestine has proven difficult. There is an unmet need for methodologies to release probes/drugs to remote regions of the gastrointestinal tract in furthering our understanding of gut health and pathogenesis. In order to address this concern, we need to know how the regional delivery of a surrogate labeled test compound is handled and in turn, if delivered locally as a liquid or powder, the dynamics of its subsequent handling and metabolism. In the studies we report on in this paper, we chose (13)C sodium acetate ((13)C-acetate), which is a stable isotope probe that once absorbed in the small intestine can be readily measured non-invasively by collection and analysis of (13)CO2 in the breath. This would provide information of gastric emptying rates and an indication of the site of release and absorptive capacity. In a series of in vitro and in vivo pig experiments, we assessed the enteric-protective properties of a commercially available polymer EUDRAGIT(®) L100-55 on gelatin capsules and also on DRcaps(®). Test results demonstrated that DRcaps(®) coated with EUDRAGIT(®) L100-55 possessed enhanced enteric-protective properties, particularly in vivo. These studies add to the body of knowledge regarding gastric emptying in pigs and also begin the process of gathering specifications for the design of a simple and cost-effective enteric-coated capsule for delivery of acid-labile macromolecules to the small intestine.
authors.affiliation: Division of Information Technology, Engineering and the Environment, School of Engineering, University of South Australia, Mawson Lakes, SA 5095, Australia; Division of Health Sciences, School of Pharmacy and Medical Science, University of South Australia, Adelaide, SA 5000, Australia; Large Animal Research and Imaging Facility, South Australian Health & Medical Research Institute (SAHMRI), Gilles Plains, SA 5086, Australia; Ian Wark Research Institute, University of South Australia, Mawson Lakes, SA 5095, Australia; Gait and Balance Research Group, Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, Melbourne, VIC 3032, Australia.
authors.forename: Darren S
authors.initials: DS
authors.lastname: Miller
authors.forename: Anne Michelle
authors.initials: AM
authors.lastname: Parsons
authors.forename: John
authors.initials: J
authors.lastname: Bresland
authors.forename: Paul
authors.initials: P
authors.lastname: Herde
authors.forename: Duc Minh
authors.initials: DM
authors.lastname: Pham
authors.forename: Angel
authors.initials: A
authors.lastname: Tan
authors.forename: Hung-yao
authors.initials: HY
authors.lastname: Hsu
authors.forename: Clive A
authors.initials: CA
authors.lastname: Prestidge
authors.forename: Tim
authors.initials: T
authors.lastname: Kuchel
authors.forename: Rezaul
authors.initials: R
authors.lastname: Begg
authors.forename: Syed Mahfuzul
authors.initials: SM
authors.lastname: Aziz
authors.forename: Ross N
authors.initials: RN
authors.lastname: Butler
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001647:Bile Acids and Salts / Q000737:chemistry*; D002214:Capsules / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D005260:Female; D007408:Intestinal Absorption / Q000502:physiology*; D046911:Macromolecular Substances / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011109:Polymethacrylic Acids / Q000737:chemistry*; D013552:Swine
chemical_list: D001647:Bile Acids and Salts; D002214:Capsules; D020099:Coated Materials, Biocompatible; D046911:Macromolecular Substances; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer
keywords: Biomarker delivery; Breath testing; Endoscopic capsule; Gastric emptying; Gastrointestinal tract; Pig