Development of a transmucosal technique for erythromycin delivery to treat gastroparesis.
Gastroparesis is a serious condition that limits meal or medication emptying from the stomach, resulting in a variety of symptoms, altered nutrition, and inconsistent medication delivery. Our aim was to develop a transmucosal system to deliver erythromycin (EM), a gastric prokinetic agent, to bypass intestinal absorption. Humans and Sprague-Dawley rats were given EM by injection, gavage, or transmucosal gel with or without permeation enhancers. Pharmacokinetics were compared between subjects and across different delivery modalities. Drug concentrations in blood were measured using a bioassay. Design of Experiment techniques were used to optimize transmucosal antibiotic delivery in the Sprague-Dawley Model. Finally, we examined the scale-up of transmucosal delivery to human patients. Transmucosal delivery of EM increased with addition of ursodeoxycholate. While EM release from gels with ursodeoxycholate was significant, it was less than by injection. Scale-up to a human model indicated that delivery of EM using this transmucosal delivery system is insufficient for clinical need. The transport of EM seems limited by its solubility in water and thickness of the epithelial cell layers. Providing successful transmucosal delivery of EM and similar molecules to humans will require more aggressive techniques to disrupt the cellular layer, or pro-drug strategies to increase lipid solubility.
McLemore
Ryan
R
Biomaterials Laboratory, Center for Interventional Biomaterials, School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona 85287, USA.
Lunt
Brian
B
Salameh
Sarah
S
DiBaise
John K
JK
Crowell
Michael D
MD
Vernon
Brent L
BL
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D064907:Diagnostic Uses of Chemicals; D004333:Drug Administration Routes; D004917:Erythromycin / Q000494:pharmacology; D005079:Excipients / Q000494:pharmacology*; D005765:Gastrointestinal Agents / Q000494:pharmacology; D018589:Gastroparesis / Q000175:diagnosis* / Q000628:therapy*; D005782:Gels / Q000494:pharmacology; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D004364:Pharmaceutical Preparations; D010829:Physiological Phenomena; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
D000900:Anti-Bacterial Agents; D064907:Diagnostic Uses of Chemicals; D005079:Excipients; D005765:Gastrointestinal Agents; D005782:Gels; D004364:Pharmaceutical Preparations; D004917:Erythromycin