Comparative in vivo study of poly(ethylene imine)/siRNA complexes for pulmonary delivery in mice

Hybrid pulmonary surfactant-coated nanogels mediate efficient in vivo delivery of siRNA to murine alveolar macrophages

“…On the other hand, the removal of excess surfactant vesicles had a negative impact on the gene silencing potential, which could possibly be related to the significantly lower intracellular siRNA levels in rAM of mice treated with the purified formulation at the early time points (4 h and 24 h). Notably, the surfactant-coated siNGs were able to induce an effective siRNA-mediated gene knockdown, reaching 70 % knockdown in the difficult to transfect rAM, at a lower instilled siRNA dose compared to earlier work [14]. Together with our in vitro findings in MH-S cells, where a strong downregulation of CD45 expression was maintained despite the hampered cellular uptake, these results jointly hint toward a beneficial effect of the pulmonary surfactant on cellular siRNA delivery.…”

“…Our results clearly revealed that excess of clinically approved pulmonary surfactant (Curosurf ® ) promoted a significant, yet conflicting impact on both the pro-inflammatory secretions and the cellular infiltrations. Although it is conceivable that the expression levels of inflammatory mediators can change as a function of time [14], we clearly observed that the decoration of NGs with a pulmonary surfactant outer layer already significantly reduced the acute cytokine and chemokine responses evoked by bare cationic NGs. Moreover, comparable expression levels were observed for both surfactant-coated NGs and purified surfactant-coated NGs corroborating the negligible proinflammatory responses upon aspiration of empty Curosurf ® vesicles, which is in agreement with earlier reports [39].…”

“…A multitude of novel siRNA nanocarriers has already been tested in vitro. Still, to date only a limited number of nanoparticles have been evaluated for local in vivo siRNA delivery to rAM, with variable success [14][15][16].…”

Screening of siRNA Nanoparticles for Delivery to Airway Epithelial Cells Using high-content Analysis

“…Previous research has demonstrated that cytotoxicity and biological activity in PEGylated PEI is dependent on both the level of PEGylation of the polymer and the molecular weight of the PEG in question [23,32]. Encouraging results have been encountered regarding both the production of genetic knockdown and the investigation of resulting toxicity of PEI-based nanoparticles [37,38]. These studies have shown that while PEGylation has the desired effect of reducing toxicity, the issue of the proinflammatory effects of the delivered particles remains a concern for future clinical applications.…”

Sistemas líquido cristalinos de geleificação in situ de administração intratumoral para liberação localizada de siRNA na terapia do câncer de pele

“…A complexação siRNA/carreador catiônico evita os problemas de repulsão pela membrana celular que tem carga residual negativa e diminui o tamanho dos ácidos nucléicos devido à condensação da molécula (BEYERLE et al, 2011;GÜNTHER et al, 2011;LIU et al, 2011;SCHROEDER et al, 2010;WONG;PELET;PUTNAM, 2007).…”