title: PLGA nanoparticles for peroral delivery: How important is pancreatic digestion and can we control it?
abstract: Biodegradable nanoparticles made of Poly(lactide-co-glycolide) are increasingly proposed for the improvement of oral drug absorption, but also as carriers for the treatment of colonic diseases. Unfortunately, our knowledge of the digestibility of PLGA-NPs is rather limited. Therefore, we investigated the impact of pancreatin on the digestibility of PLGA-NPs stabilized with different emulsifiers. The pancreatin induced degradation was monitored by the pH-stat method and an enzymatic l-lactic acid assay. A high digestibility was found for poloxamer 188 and polysorbate 80 stabilized PLGA-NPs. The digestion could be blocked by Orlistat, indicating a major role of pancreatic lipase. PLGA-NPs stabilized with Poly(vinyl alcohol) (=PVA) were not digested at comparable surfactant concentrations (0.6%). However, PLGA-NPs stabilized with very low amounts of PVA (0.1%) were digestible. In conclusion, PLGA-NPs are substrates for the pancreatic lipase. The digestibility can be enhanced or blocked by the proper selection of the surfactant composition and concentration.
authors.affiliation: Institute of Pharmacy, Faculty of Biosciences, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, D-06120 Halle (Saale), Germany. Electronic address: anika.mante@medizin.uni-leipzig.de.
authors.forename: Anika
authors.initials: A
authors.lastname: Mante
authors.affiliation: Institute of Pharmacy, Faculty of Biosciences, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, D-06120 Halle (Saale), Germany. Electronic address: martha.heider@pharmazie.uni-halle.de.
authors.forename: Martha
authors.initials: M
authors.lastname: Heider
authors.affiliation: Institute of Pharmacy, Faculty of Biosciences, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, D-06120 Halle (Saale), Germany. Electronic address: christin.zlomke@pharmazie.uni-halle.de.
authors.forename: Christin
authors.initials: C
authors.lastname: Zlomke
authors.affiliation: Institute of Pharmacy, Faculty of Biosciences, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, D-06120 Halle (Saale), Germany. Electronic address: http://pharmtech.pharmazie.uni-halle.de.
authors.forename: Karsten
authors.initials: K
authors.lastname: Mäder
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000737:chemistry*; D008049:Lipase / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology; D010194:Pancreatin / Q000737:chemistry; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry; D011142:Polyvinyl Alcohol / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry; D013552:Swine
chemical_list: D004337:Drug Carriers; D011108:Polymers; D011136:Polysorbates; D013501:Surface-Active Agents; D020442:Poloxamer; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D010194:Pancreatin; D011142:Polyvinyl Alcohol; D008049:Lipase
keywords: Biodegradable polymers; Lipase; Nanoparticles; Oral delivery; PLGA; Pancreatic lipase; Pancreatin, digestion; Peroral; Poly(lactide-co-glycolide)