title: Stability of bovine lactoferrin in luminal extracts and mucosal homogenates from rat intestine: a prelude to oral absorption.
abstract: Oral delivery is the most common method for bovine lactoferrin (bLf) administration. However, the presence of proteolytic enzymes in the stomach and intestine limits the effective absorption of bLf within the gastrointestinal (GI) tract. To determine the extent of bLf proteolysis, several digestion models were developed using luminal extracts and mucosal homogenates isolated from four regions of rat intestine: duodenum, jejunum, ileum, and proximal colon. The kinetics of bLf degradation followed a pseudo-first-order rate, and almost complete hydrolysis of bLf was observed in the luminal extracts, indicating that bLf is more susceptive to luminal peptidases rather than mucosal enzymes. Moreover, a significant reduction in bLf proteolysis was observed in the presence of soybean trypsin inhibitor (SBTI), bestatin, and bacitracin, suggesting that there exist trypsin-like and aminopeptidase-like proteases, which play a key role in the degradation of bLf in the intestine. Lactoferrin was then encapsulated in several lipid-based delivery systems including liposomes and solid lipid particles (SLPs) with polymer modification, showing at least 50% of intact bLf remaining after 6 h of digestion compared with native bLf. These findings suggest that particle encapsulation may modulate protein digestion and possibly achieve sufficient oral bioavailability of bLf.
authors.affiliation: Faculty of Medical and Health Science, School of Pharmacy, The University of Auckland, Auckland, 1142, New Zealand.
authors.forename: Xudong
authors.initials: X
authors.lastname: Yao
authors.forename: Craig
authors.initials: C
authors.lastname: Bunt
authors.forename: Jillian
authors.initials: J
authors.lastname: Cornish
authors.forename: Siew-Young
authors.initials: SY
authors.lastname: Quek
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Wen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000201:enzymology / Q000378:metabolism*; D007700:Kinetics; D007781:Lactoferrin / Q000008:administration & dosage / Q000032:analysis / Q000378:metabolism*; D008297:Male; D055550:Protein Stability / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004791:Enzyme Inhibitors; D007781:Lactoferrin
keywords: bovine lactoferrin; enzyme inhibitor; particulate delivery system; proteolysis; pseudo-first-order rate