Surface modification of microspheres with steric stabilizing and cationic polymers for gene delivery

Area of Science:

• Biomaterials Science
• Vaccine Technology
• Nanotechnology

Background:

• Poly( D,L-lactide- co-glycolide) (PLG) microspheres are investigated for DNA vaccine delivery.
• Surface modification is crucial for improving DNA loading and cellular interaction.

Purpose of the Study:

• To develop surface-modified PLG microspheres for DNA vaccine applications.
• To optimize the incorporation of cationic functionalities for enhanced DNA surface loading.

Main Methods:

• Utilized the oil-in-water solvent evaporation method for PLG microsphere fabrication.
• Introduced various polycations (PEI, poly( L-lysine), trimethyl chitosan, (dimethylamino)ethyl methacrylate) into the water phase.
• Systematically evaluated production variables including polycation type, molecular weight, and concentration.

Main Results:

• Achieved microsphere properties suitable for antigen-presenting cell uptake and good colloidal stability.
• Demonstrated that polycation molecular weight and concentration influence surface polycation content and DNA binding.
• Attained nearly 100% DNA loading efficiency under optimized conditions in physiologically acceptable buffers.
• Observed increased aggregation with decreased microsphere size and higher polycation content.
• Confirmed successful internalization of surface-loaded DNA into target cells via endocytosis.

Conclusions:

• Surface modification of PLG microspheres with polycations is a viable strategy for DNA vaccine development.
• Optimized conditions yield microspheres with high DNA loading efficiency and cellular uptake.
• Further increases in DNA loading may lead to incomplete charge neutralization, potentially affecting in vivo stability.