Nasal absorption of selected amino acids and peptides in rats

Parkpoom Tengamnuay, Purdue University

Abstract

In recent years nasal administration of peptides and proteins has received greater attention. However, little is still known about the nature of barriers existing in the nasal mucosa as well as mechanisms by which these molecules are absorbed. Studies were then initiated to investigate the role of nasal mucosa in the transport of biomolecules such as amino acids and peptides. With a technique involving in situ perfusion of the rat nasal cavity, aromatic amino acids like phenylalanine and tyrosine were found to be absorbed by saturable transport processes. The systems appeared to be more effective for the L-amino acids than for the D-enantiomers. At least one common carrier system was present for active, Na$\sp+$-dependent transport of L-Tyr and L-Phe. On the other hand, nasal absorption of dipeptides was very poor even in the absence of enzymatic degradation and thus required certain types of absorption promoters. Adjuvants like mixed micelles containing bile salt and unsaturated polar lipids significantly enhanced nasal absorption of (DArg$\sp2$) -Kyotorphin, an enzymatically stable model dipeptide. The promoting effect appeared to be synergistic and reversible. In addition, in vivo nasal absorption of insulin, a pancreatic peptide hormone, was also found to be significantly improved in the presence of mixed micelles with a concomitant hypoglycemic effect. Histopathologic examination revealed that the extent of mucosal alterations caused by mixed micelles was mild to moderate and appeared to be repairable. With further optimization, the use of adjuvant combination such as the ones studied may show promise as a safe and effective means to promote nasal absorption of peptides and proteins.

Degree

Ph.D.

Advisors

Mitra, Purdue University.

Subject Area

Pharmaceuticals

COinS