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Using Polystyrene-block-poly(acrylic acid)-coated Metal Nanoparticles as Monomers for Their Homo- and Co-polymerization
Published on: July 9, 2015
Development of a novel method for the preparation of thiolated polyacrylic acid nanoparticles
Melanie Greindl1, Andreas Bernkop-Schnürch
1Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University Innsbruck, Innrain 52, Josef-Möller-Haus, 6020 Innsbruck, Austria.
Purpose:
To develop a novel method for the preparation of thiolated polyacrylic acid nanoparticles via ionic gelation.
Materials And Methods:
In a first step nanoparticles were generated by ionotropic gelation of polyacrylic acid (PAA) of three different molecular weights (100, 240 and 450 kDa) and various cations including Ca2+, Mg2+, Zn2+, Al3+ and Fe3+. Via in vitro characterization of the particles (particle size, size distribution and zeta potential) the optimal preparation conditions were established. Taking into consideration, that thiolated polyacrylic acid (PAA-Cys) displays higher mucoadhesive and permeation enhancing properties than unmodified PAA, PAA-Cys nanoparticles were produced in the same manner with Ca2+, as the most promising results concerning particle size and stability of particles could be achieved with this ionic crosslinker. The nanoparticles were stabilized via the formation of inter- and intrachain disulfide bonds within these particles due to oxidation with H2O2. Ca2+ was removed proximately by the addition of EDTA and exhaustive dialysis.
Results:
Using the preparation method described above PAA-Cys nanoparticles of a mean diameter of about 220 nm (PAA(100)-Cys), 250 nm (PAA(240)-Cys) and 295 nm (PAA(450)-Cys) can be generated. In comparison to PAA nanoparticles ionically crosslinked with Ca2+, the removal of the crosslinker Ca2+ from PAA-Cys particles led to a nearly three-fold decrease in the zeta potential, from about -7 up to -20 mV. Apart from this advantage, covalently crosslinked PAA-Cys nanoparticles were more firm as they remained stable when incubated in hydrochloride solution, whereas ionically crosslinked particles dissolved at pH lower than 5.
Conclusions:
This novel nanoparticulate delivery system seems to be a promising vehicle for the administration of therapeutic proteins, genes and antigens via mucosal membranes.
