Targeted PLGA microparticles as a novel concept for treatment of lactose intolerance

BackgroundPeroral β-galactosidase preparations for the management of lactose intolerance need to be administered in large doses (1500 to 6000 U) immediately before or together with a lactose-containing meal.AimTherefore, this work aimed at developing an innovative long-acting formulation. For this purpose, biodegradable polymeric microcarriers were functionalized with β-galactosidase and targeted with wheat germ agglutinin (WGA) for bioadhesion and thus prolonged residence time in the small intestine.MethodsSpray-dried poly(d,l-lactide-co-glycolide) (PLGA) particles with 2.78 ± 1.05 µm in diameter were functionalized with β-galactosidase from Kluyveromyces lactis and WGA using different types of spacers (polyethyleneimine, hexamethylene diamine, 6-aminocaproic acid) and coupling methods (carbodiimide and glutaraldehyde). The particle-bound enzyme activity was determined, and the bioadhesive characteristics were assessed by interaction with mucin coatings and Caco-2 cell monolayers.ResultsUp to 1470 U β-galactosidase per gram PLGA were immobilized. The best results were obtained with hexamethylene diamine as a spacer applying the carbodiimide method. Thereby, a nearly 6-fold increase in enzyme activity was obtained as compared to particles without spacer. Upon targeting with WGA, binding to artificial human intestinal epithelium was increased considerably.ConclusionsFor the delivery of β-galactosidase WGA-targeted PLGA microparticles were prepared, which represent promising candidates for a convenient biomimetic treatment regimen of lactose intolerance.

Figure optionsDownload as PowerPoint slideBring it back to where it used to be: a biomimetic concept for longer-acting peroral lactase substitution based on lectin-mediated targeting of biodegradable enzyme carriers to the intestinal brush border.