Oral delivery of salmon calcitonin.
Calcitonin plays a crucial role in both calcium homeostasis and bone remodeling. Establishing an oral delivery system for CT is of great importance since CT is currently administered only parenterally or nasally. Poor absorption and rapid proteolytic degradation have impeded the clinical development of an orally administered sCT drug product. Potential approaches to enhance sCT absorption include the use of formulation additives in the drug product to transiently modulate the intestinal environment or targeting specific intestinal regions that may have favorable peptide delivery properties (e.g., low residual volume, high absorptive surface area or reduced enzymatic activity). Potential approaches to limit the activity of intestinal enzymes include adjusting the pH of the intestinal contents to the pH minima of specific enzymes or maintaining high local drug concentrations in order to saturate enzyme systems. In this review, pharmacokinetic studies elucidating the rate-limiting steps for achieving adequate sCT oral bioavailability are detailed. Further, several approaches for enhancing the oral absorption of sCT are presented. Specific emphasis is placed on regio-specific targeting (e.g., intestinal regional differences in dilution and spreading, etc.) and modulation of the intestinal environment (e.g., changing pH, etc.). The approaches are evaluated in in vitro and in vivo models. Finally, this paper closes with a brief section of concluding remarks.
Lee
Y H
YH
Department of Pharmaceutics, Rutgers University, College of Pharmacy, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA.
Sinko
P J
PJ
D000284:Administration, Oral; D000818:Animals; D002116:Calcitonin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D005769:Gastrointestinal Motility; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D008099:Liver / Q000378:metabolism; D012869:Skin Absorption
C028815:salmon calcitonin; D002116:Calcitonin