A highly stable Yarrowia lipolytica lipase formulation for the treatment of pancreatic exocrine insufficiency.
Yarrowia lipolytica lipase has been assumed to be a good candidate for the treatment of fat malabsorption in patients with pancreatic insufficiency. Nevertheless, no systematic studies on its stability under physiological conditions pertaining to the human GI (gastrointestinal) tract have been published. Stability of various Y. lipolytica lipase powder formulations at various physiological pH values as well as the effect of digestive proteases and bile salts on enzyme activity were investigated. Results were compared with those obtained from another competing fungal lipase sourced from Candida rugosa. Among the studied formulations, Y. lipolytica lipase stabilized with gum arabic and skimmed milk powder was the most promising powder formulation. Under acidic conditions (pH 3-5), this formulation showed higher stability than those observed with the other Y. lipolytica lipase formulations and C. rugosa lipase. In addition, in the presence of gum arabic and skimmed milk powder as additives, Y. lipolytica lipase exhibited markedly higher resistance to pepsin, trypsin and chymotrypsin actions. Resistance to proteolytic degradation by digestive proteases was also by far higher than that observed with C. rugosa lipase. Similar behaviour was, however, observed when these two fungal lipases were incubated with increased concentrations of bile salts. Residual lipase activity of both fungal lipases showed a slight decrease in NaTDC (sodium taurodeoxycholate) concentration above 4 mM. Consequently, Y. lipolytica lipase formulated with gum arabic and milk powder seemed to have great potential for use as a therapeutic tool for patients with pancreatic insufficiency.
Turki
Saoussen
S
Fermentation Unit, Institut Pasteur de Tunis, 1002 Tunis Belvédère, Tunisia.
Mrabet
Ghada
G
Jabloun
Zeineb
Z
Destain
Jacqueline
J
Thonart
Philippe
P
Kallel
Héla
H
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D002175:Candida / Q000201:enzymology; D002626:Chemistry, Pharmaceutical; D002918:Chymotrypsin / Q000378:metabolism; D056947:Enzyme Replacement Therapy / Q000379:methods*; D004795:Enzyme Stability; D010188:Exocrine Pancreatic Insufficiency / Q000188:drug therapy* / Q000201:enzymology; D006170:Gum Arabic / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008049:Lipase / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D008892:Milk / Q000378:metabolism; D010434:Pepsin A / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism; D025062:Yarrowia / Q000201:enzymology*
D001647:Bile Acids and Salts; D006170:Gum Arabic; D008049:Lipase; D002918:Chymotrypsin; D014357:Trypsin; D010434:Pepsin A