TY  - JOUR
U1  - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed)
A1  - Guțoaia, Andra
A1  - Schuster, Liane
A1  - Margutti, Simona
A1  - Laufer, Stefan
A1  - Schlosshauer, Burkhard
A1  - Krastev, Rumen
A1  - Stoll, Dieter
A1  - Hartmann, Hanna
T1  - Fine-tuned PEGylation of chitosan to maintain optimal siRNA-nanoplex bioactivity
JF  - Carbohydrate polymers
N2  - Polyethylene glycol (PEG) is a widely used modification for drug delivery systems. It reduces undesired interaction with biological components, aggregation of complexes and serves as a hydrophilic linker of ligands for targeted drug delivery. However, PEGylation can also lead to undesired changes in physicochemical characteristics of chitosan/siRNA nanoplexes and hamper gene silencing.
To address this conflicting issue, PEG-chitosan copolymers were synthesized with stepwise increasing degrees of PEG substitution (1.5% to 8.0%). Subsequently formed PEG-chitosan/siRNA nanoplexes were characterized physicochemically and biologically. The results showed that small ratios of chitosan PEGylation did not affect nanoplex stability and density. However, higher PEGylation ratios reduced nanoplex size and charge, as well as cell uptake and final siRNA knockdown efficiency.
Therefore, we recommend fine-tuning of PEGylation ratios to generate PEG-chitosan/siRNA delivery systems with maximum bioactivity. The degree of PEGylation for chitosan/siRNA nanoplexes should be kept low in order to maintain optimal nanoplex efficiency.
KW  - chitosan
KW  - PEGylated chitosan
KW  - siRNA-delivery
KW  - nanoplex functionality
KW  - gene silencing
Y1  - 2016
SN  - 0144-8617
SS  - 0144-8617
U6  - https://doi.org/10.1016/j.carbpol.2016.01.010
DO  - https://doi.org/10.1016/j.carbpol.2016.01.010
VL  - 143
SP  - 25
EP  - 34
S1  - 10
PB  - Elsevier
CY  - Amsterdam
ER  -