Stability of Bovine Lactoferrin in Luminal Extracts and Mucosal Homogenates from Rat Intestine: A Prelude to Oral Absorption |
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Authors: | Xudong Yao Craig Bunt Jillian Cornish Siew‐Young Quek Jingyuan Wen |
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Affiliation: | 1. Faculty of Medical and Health Science, School of Pharmacy, The University of Auckland, , Auckland, 1142 New Zealand;2. Faculty of Agriculture and Life Science, Lincoln University, , Lincoln, 7647 New Zealand;3. Faculty of Medical and Health Science, School of Medicine, The University of Auckland, , Auckland, 1142 New Zealand;4. School of Chemical Science, The University of Auckland, , Auckland, 1142 New Zealand |
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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. |
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Keywords: | bovine lactoferrin enzyme inhibitor particulate delivery system proteolysis pseudo‐first‐order rate |
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