Pluronic-based cationic block copolymer for forming pDNA polyplexes with enhanced cellular uptake and improved...

Area of Science:

• Biomaterials Science
• Gene Therapy
• Polymer Chemistry

Background:

• Cationic polymers are explored as non-viral gene delivery vectors, forming polyplexes with DNA.
• PEGylation enhances polyplex stability but often reduces transfection efficiency due to poor cellular uptake and endosomal escape.

Purpose of the Study:

• To investigate if Pluronic block copolymers can improve the transfection efficiency of gene delivery polyplexes.
• To compare the gene delivery performance of Pluronic P85-based and PEG-based cationomers.

Main Methods:

• Synthesis of Pluronic P85- and PEG-based cationomers with poly{N-[N-(2-aminoethyl)-2-aminoethyl] aspartamide} (P[Asp(DET)]) cationic blocks.
• Formation and characterization of polyplexes with plasmid DNA (pDNA).
• Evaluation of polyplex stability, cellular internalization, and transfection efficiency in vitro.

Main Results:

• Pluronic P85-based polyplexes demonstrated significantly higher transfection efficiency compared to PEG-based polyplexes.
• PEG-based polyplexes exhibited greater stability than P85-based polyplexes.
• Enhanced gene delivery by P85-based polyplexes correlated with increased cellular internalization.

Conclusions:

• Pluronic P85 incorporation into cationic polymers can enhance gene delivery by promoting cellular uptake.
• Pluronic P85-based polyplexes represent a viable alternative to PEGylated systems for improved gene therapy efficacy.
• The trade-off between stability and transfection efficiency highlights the importance of polymer design in gene delivery systems.