PEGylated gene carriers in serum under shear flow

Area of Science:

• Biomaterials Science
• Nanotechnology
• Biophysics

Background:

• The behavior of drug/gene carriers in blood under shear stress is not well understood.
• Understanding these dynamics is crucial for designing effective gene delivery systems.

Purpose of the Study:

• To investigate the dynamic behavior of poly(ethylene glycol)-b-poly(l-lysine) (PEG-PLL)/DNA complexes under shear flow in fetal bovine serum (FBS).
• To elucidate the role of PEG layer length in the shear-induced aggregation of gene carriers.

Main Methods:

• Complexes of DNA with PEG-PLL of varying PEG lengths were subjected to different shear rates in the presence of FBS.
• Dynamic behavior and aggregation were analyzed at shear rates mimicking blood flow conditions.

Main Results:

• PEG5k-PLL/DNA complexes showed shear-dependent aggregation, with initial disturbance of the PEG layer followed by core exposure and serum-induced aggregation.
• Aggregation dynamics varied with PEG length: insufficient PEG (PEG2k-PLL/DNA) led to pre-shear aggregation, while excessive PEG (PEG10k-PLL/DNA) prevented tertiary aggregation.
• The DNA/PLL core demonstrated resilience to shear forces up to 500 s-1, undergoing reorganization and tertiary aggregation.

Conclusions:

• The length and stability of the PEG layer critically influence the shear-induced aggregation of PEG-PLL/DNA complexes in serum.
• These findings provide insights into the mechanism of shear effects on gene carriers, aiding in the design of more efficacious delivery systems.