title: A new drug delivery system targeting ileal epithelial cells induced electrogenic sodium absorption: possible promotion of intestinal adaptation.
abstract: We previously demonstrated the induction of the epithelial sodium channel, prostasin, and 11beta-hydroxysteroid dehydrogenase type 2 and activation of sodium transport mediated by those molecules in the remnant ileum after total proctocolectomy. The aims of the present study were to develop a new drug delivery system that targets ileal epithelial cells and to enhance local mineralocorticoid action without systemic effects. Orally administered D-aldosterone-containing D,L-lactide/glycolide acid copolymer microspheres are absorbed in the rat terminal ileum and released aldosterone. Blood and terminal ileal tissues were collected 2 weeks after the administration of the microspheres, and the aldosterone concentrations, mRNA, and protein expressions of the above molecules and sodium transport were evaluated. Significantly high levels of tissue aldosterone in the absence of elevated plasma levels were detected in the microspheres-treated rats. Epithelial mRNA and protein expression of the above molecules increased significantly in the microspheres-treated animals. Electrogenic sodium transport in the ileum was enhanced in the microspheres-treated rats. Aldosterone-containing microspheres successfully induced the expression of the above molecules and activated sodium transport in the ileal mucosa, both of which are essential for intestinal adaptation. Pre- and/or postoperative treatment with this drug may compensate for the excessive loss of sodium and water following proctocolectomy.
authors.affiliation: Department of Surgery, Tohoku University, Graduate School of Medicine, 1-1, Seiryomachi, Aobaku, Sendai 980-8574, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Haneda
authors.forename: Kouhei
authors.initials: K
authors.lastname: Fukushima
authors.forename: Yuji
authors.initials: Y
authors.lastname: Funayama
authors.forename: Chikashi
authors.initials: C
authors.lastname: Shibata
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Takahashi
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.forename: Iwao
authors.initials: I
authors.lastname: Sasaki
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000032:analysis / Q000378:metabolism; D000042:Absorption; D000222:Adaptation, Physiological / Q000187:drug effects; D000450:Aldosterone / Q000008:administration & dosage / Q000032:analysis / Q000097:blood; D000818:Animals; D003082:Colectomy; D016503:Drug Delivery Systems; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D053503:Epithelial Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D007082:Ileum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D008863:Microspheres; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012007:Rectum / Q000601:surgery; D012697:Serine Endopeptidases / Q000032:analysis / Q000378:metabolism; D012964:Sodium / Q000032:analysis / Q000378:metabolism; D051269:Sodium-Glucose Transporter 1 / Q000032:analysis; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis; D000099271:Prostasin
chemical_list: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D000450:Aldosterone; D053503:Epithelial Sodium Channels; D019344:Lactic Acid; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D012333:RNA, Messenger; D012697:Serine Endopeptidases; D012964:Sodium; D051269:Sodium-Glucose Transporter 1; D000254:Sodium-Potassium-Exchanging ATPase; D000099271:Prostasin; C503554:Atp1b1 protein, rat