Anti-inflammatory effect of anti-tnf- α cationic phosphorous dendrimers nanocomplexes administered intranasally in a murine acute lung injury model.

ANTI-INFLAMMATORY EFFECT OF ANTI-TNF-α CATIONIC PHOSPHOROUS DENDRIMERS NANOCOMPLEXES ADMINISTERED INTRANASALLY IN A MURINE ACUTE LUNG INJURY MODEL. Biomacromolecules. 2017 Jun 22;: Authors: Bohr A, Tsapis N, Andreana I, Chamarat A, Foged C, Delomenie C, Noiray M, El Brahmi N, Majoral JP, Mignani S, Fattal E Abstract Inflammation is an essential component of many lung diseases, including asthma, chronic obstructive pulmonary disease (COPD) or acute lung injury. Our purpose was to design efficient carriers for lung delivery of small interfering RNA (siRNA) targeting tumor necrosis factor (TNF-α) in an acute lung injury model. To achieve this goal, two different types of phosphorus-based dendrimers with either pyrrolidinium or morpholinium as terminal protonated amino groups were selected for their better biocompatibility compared to other dendrimers. Dendriplexes containing pyrrolidinium surface groups demonstrated a stronger siRNA complexation, a higher cellular uptake and enhanced in vitro silencing efficiency of TNF-α in the lipopolysaccharide (LPS)-activated mouse macrophage cell line RAW264.7, compared to morpholinium-containing dendriplexes. The better performance of the pyrrolidium dendriplexes was attributed to their higher pKa value leading to a stronger siRNA complexation and improved protection against enzymatic degradation resulting in a higher cellular uptake. The superior silencing effect of the pyrrolidinium dendriple...
Source: Biomacromolecules - Category: Biochemistry Authors: Tags: Biomacromolecules Source Type: research