Despite their wide variety of applications, efficacy of nano-sized drug delivery systems is severely limited by different barriers inside the body. One major obstacle is the extracellular matrix (ECM). Here, small, neutral and hydrophilic nanoparticles are advantageous regarding particle transport [1]. Our aim is to develop a model gene carrier system based on anionic nanoparticles with a coating of branched poly(ethylene imine) (brPEI) which is able to complex nucleic acids [2]. We focus on modifying surface properties of these nanoparticles through a neutral poly(ethylene glycol) (PEG) shielding to improve their mobility in charged matrices.Anionic silica nanoparticles were coated with one layer of brPEI or fluorescein isothiocyanate (FITC)-labeled brPEI. PEGylation of PEI-coated particles took place in borate buffer using methoxy PEG succinimidyl active esters with different molecular weights. Subsequently, particle characterization was performed by dynamic light scattering (DLS). To estimate the mobility of nanoparticles, fluorescence recovery after photobleaching (FRAP) was conducted in various ECM-like gels.According to our DLS measurements the size of brPEI-coated particles increased rapidly after the first day of storage, whereby PEGylated particles exhibited steady diameters for at least seven days. Furthermore, lower polydispersity indices were observed for PEGylated samples. Regarding the zeta-potential a decrease from positive to neutral values was measured depending on the degree of PEGylation. In our FRAP experiments we could show that fluorescence recovery was more effective for higher PEGylation degrees.We proved that the PEG shielding of brPEI-coated particles prevented colloidal instability and aggregation. The surface charge decreased as a function of the amount of bound PEG molecules on the particles. In addition, surface properties were successfully modified to achieve higher particle mobilities in ECM.[1] S. L�lu et al.: Biomolecules (2011), 12, 3656-3665[2] S. Bauhuber et al.: JConRel (2012), 162, 446-455

Influence of PEGylation degree on the mobility of polycationic nanoparticles

248th National Meeting (2014)

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