Gene expression mediated by dendrimer/DNA complexes encapsulated in biodegradable polymer microspheres

Area of Science:

• Biomaterials Science
• Gene Delivery Systems
• Nanotechnology

Background:

• Gene therapy requires efficient and safe delivery vectors.
• Polyamidoamine (PAMAM) dendrimers are promising non-viral gene carriers.
• Protecting DNA complexes is crucial for maintaining bioactivity.

Purpose of the Study:

• To develop a novel method for fabricating gene-loaded microspheres.
• To evaluate the gene transfection efficiency of protected PAMAM/DNA complexes.
• To assess the degradation properties and DNA bioactivity preservation.

Main Methods:

• Fabrication of microspheres using an ultrasonic dispersion method.
• Encapsulation of polyamidoamine (PAMAM) dendrimer/DNA complexes protected by poly-alpha,beta-[N-(2-hydroxyethyl)-L-aspartamide] (PHEA).
• Utilizing cholic acid functionalized star poly(DL-lactide) for microsphere matrix, enabling surface erosion.

Main Results:

• The ultrasonic method produced microspheres without toxic organic solvents.
• PHEA-protected PAMAM/DNA complexes demonstrated significantly higher in vitro gene transfection activity.
• Effective gene expression (pGL3-Luc) was observed in HEK293 cells using the microspheres.

Conclusions:

• The ultrasonic dispersion method is a convenient and effective technique for fabricating gene-loaded microspheres.
• PHEA protection enhances the transfection efficacy of PAMAM/DNA complexes.
• The developed microspheres are suitable for gene delivery, preserving DNA bioactivity and offering controlled release via surface erosion.