A new drug delivery system targeting ileal epithelial cells induced electrogenic sodium absorption: possible promotion of intestinal adaptation.
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.
Haneda
Sho
S
Department of Surgery, Tohoku University, Graduate School of Medicine, 1-1, Seiryomachi, Aobaku, Sendai 980-8574, Japan.
Fukushima
Kouhei
K
Funayama
Yuji
Y
Shibata
Chikashi
C
Takahashi
Ken-Ichi
K
Tabata
Yasuhiko
Y
Sasaki
Iwao
I
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
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