کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1425511 | 986768 | 2010 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Targeted PLGA microparticles as a novel concept for treatment of lactose intolerance Targeted PLGA microparticles as a novel concept for treatment of lactose intolerance](/preview/png/1425511.png)
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.
Journal: Journal of Controlled Release - Volume 147, Issue 2, 15 October 2010, Pages 187–192