Abstract
AbstractThis paper deals with a concept to improve the loading capability of cationic nanohydrogel particles with siRNA. For this purpose, a new tetrafunctional crosslinker is synthesized via a peptide coupling approach using lysine and spermine derivatives. Applying this four‐arm crosslinker to the particle synthesis makes it possible to perform the crosslinking with an excess or a deficit of the crosslinker. This allows for varying numbers of cationic groups per cationic core and its crosslinking density while the stability of the carrier system remains. The obtained cationic nanohydrogel particles are narrowly distributed in size as determined by dynamic light scattering measurements. Zeta potential measurements confirm the cationic nature of these carriers (ζ > +30 mV) and the ability to form complex anionic siRNA (agarose gel electrophoresis). As a result, it becomes possible to increase the siRNA loading by a factor of four by varying the composition of the crosslinked core. Such an increased siRNA loading should lead to an improved therapeutic gene knockdown effect.
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