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.