Development of bioadhesive amino-pegylated poly(anhydride) nanoparticles designed for oral DNA delivery

Abstract

Amino-pegylated poly(methyl vinyl ether-co-maleic anhydride) nanoparticles were prepared applying a solvent displacement method. The surface charge of the resulting pegylated particles was considerably higher (−2.7 mV) than that of the non-pegylated (−33.5 mV). After oral administration to rats the amino-pegylated nanoparticles exhibited great ability for bioadhesive interactions with the gastrointestinal mucosa. Furthermore, fluorescence microscopy revealed that the amino-pegylated were able to cross the cellular membrane of the absorptive enterocytes. Genomic salmon testes DNA was associated to the amino-pegylated poly(anhydride) particles by applying two procedures: (i) incubation of aqueous DNA solution with the freshly formed amino-pegylated particles; and (ii) initial incubation of DNA and DAP-PEG simultaneously, followed by blending with preformed non-pegylated particles. Gel electrophoresis showed that both methods were safe and DNA integrity was not affected. Based on the results describing their adhesive properties and intracellular transport, the amino-pegylated nanoparticles were considered as a suitable carrier for DNA.