Biodegradable nanoparticles modified by branched polyethylenimine for plasmid DNA delivery

Area of Science:

• Biomaterials Science
• Nanotechnology
• Gene Delivery Systems

Background:

• Poly(lactic-co-glycolic)-acid (PLGA) nanoparticles are promising for gene delivery.
• Comparing different PLGA nanoparticle formulations is crucial for optimizing transfection efficiency.
• Understanding pDNA interaction with PLGA nanoparticles impacts gene delivery efficacy.

Purpose of the Study:

• To comparatively evaluate two PLGA nanoparticle (NP)-based gene delivery systems: plasmid DNA (pDNA) encapsulated PLGA NPs (PLGA-E) and surface adsorbed pDNA on PLGA-BPEI NPs (PLGA-BPEI).
• To determine the optimal formulation for transfection efficiency.
• To investigate pDNA internalization, intracellular release, and colloidal stability.

Main Methods:

• Formulation of PLGA-E and PLGA-BPEI nanoparticles.
• Characterization using zeta-potential, particle size, and DNase I protection assays.
• In vitro pDNA release studies at pH 7.4 and pH 5.0.
• In vitro gene transfection efficiency studies in NIH3T3 and HEK293 cells.
• Cell viability (MTT assay) and intracellular localization (confocal microscopy) assessments.

Main Results:

• BPEI chain length significantly influenced pDNA loading, condensation, and protection in PLGA-BPEI NPs.
• PLGA-BPEI NPs showed enhanced pDNA protection and pH-triggered release compared to PLGA-E.
• Time-dependent transfection efficiencies varied with cell type and serum presence, with PLGA-BPEI generally showing higher efficacy.
• Colloidal stability was dependent on serum concentration.

Conclusions:

• PLGA-BPEI nanoparticles offer superior pDNA protection and enhanced gene delivery compared to PLGA-E formulations.
• The BPEI component plays a critical role in optimizing PLGA-based gene delivery systems.
• These findings provide valuable insights for developing effective nanoparticle-based gene therapies.