posted on 2013-11-11, 00:00authored byBuddhadev Layek, Jagdish Singh
The major goal of this study is to
design, synthesize, and evaluate
linoleic acid and penetratin dual-functionalized chitosan (CS-Lin-Pen)
as a nonviral gene carrier. The amphiphilic CS-Lin-Pen self-assembles
to form cationic micelles in an aqueous environment. These polymeric
micelles exhibited excellent hemocompatibility and cell viability,
as evaluated by in vitro hemolysis and MTT assay, respectively. When
CS-Lin-Pen micelles were added to plasmid DNA (pDNA) solution, the
electrostatic interaction between the cationic micelles and anionic
pDNA led to the formation of stable CS-Lin-Pen/pDNA polyplexes with
∼100 nm in size. The resultant polyplexes demonstrated ∼5-fold
higher cellular uptake as compared to unmodified chitosan. Furthermore,
CS-Lin-Pen micelles showed efficient protection of pDNA from DNase
I attack and exhibited ∼34–40-fold higher transfection
in comparison with unmodified chitosan in HEK 293, CHO, and HeLa cells.
These findings illustrate that the CS-Lin-Pen micelles could be exploited
as a potential nonviral vector for efficient gene therapy.