title: pH-Triggered release from surface-modified poly(lactic-co-glycolic acid) nanoparticles.
abstract: Nanoparticles (NP) of poly(lactic-co-glycolic acid) (PLGA) represent a promising biodegradable drug delivery system. We suggest here a two-step release system of PLGA nanoparticles with a pH-tunable polymeric shell, providing an initial pH-triggered step, releasing a membrane-toxic cationic compound. PLGA nanoparticles are coated by polyelectrolytes using the layer-by-layer self-assembly technique, employing poly(acrylic acid) (PAA) as a pH-sensitive component and poly(diallyldimethylammonium chloride) (PDADMAC) as the releasable polycation. The pH during multilayer deposition plays a major role and influences the titration curve of the layer system. The pH-tunability of PAA is intensively investigated with regard to the pH region, in which the particle system becomes uncharged. The isoelectric point can be shifted by employing suitable deposition pH values. The release is investigated by quantitative (1)H NMR, yielding a pH-dependent release curve. A release of PDADMAC is initiated by a decrease of the pH value. The released amount of polymer, as quantified by (1)H NMR analysis, clearly depends on the pH value and thus on the state of deprotonation of the pH-sensitive PAA layer. Subsequent incubation of the nanoparticles with high concentrations of sodium chloride shows no further release and thus demonstrates the pH-driven release to be quantitative.
authors.affiliation: Institute of Physical Chemistry, University of Muenster, Corrensstraße 28/30, 48149 Münster, Germany; Institute of Pharmaceutical Technology and Biopharmacy, University of Muenster, Corrensstraße 48, 48149 Münster, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Häuser
authors.affiliation: Institute of Pharmaceutical Technology and Biopharmacy, University of Muenster, Corrensstraße 48, 48149 Münster, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Langer
authors.affiliation: Institute of Physical Chemistry, University of Muenster, Corrensstraße 28/30, 48149 Münster, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Schönhoff
keywords: PLGA nanoparticles; layer-by-layer self-assembly; pH-triggered release; polyelectrolyte multilayers; weak polyelectrolyte