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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.
This review gives a short overview of the physical processes involved in the formation of the polyelectrolyte multilayers (PEMs) and their destruction. These two processes are vital for the formation of PEMs with desired physical and chemical structures, and for loading them with active substances and their spatial controlled release. It includes a survey of the physical and chemical properties that are key points for controlling film nanostructure in relation to biological processes and different possibilities for controlling cell behavior by means of film composition, bioactivity, mechanical properties, and three-dimensional organization.