A co-delivery platform based on plasmid DNA peptide-surfactant complexes: formation, characterization and release...

Area of Science:

• Biomedical Engineering
• Drug Delivery Systems
• Nanotechnology

Background:

• Cell-penetrating peptides, like TAT, show promise for intracellular delivery.
• Plasmid DNA (pDNA) delivery faces challenges with particle size and pDNA immobilization.
• Optimizing delivery systems is crucial for advancing therapeutic efficacy.

Purpose of the Study:

• To investigate the pDNA condensation ability of TAT peptide for intracellular delivery.
• To enhance the performance of TAT peptide-based delivery systems using surfactants.
• To evaluate the potential of the developed platform for therapeutic payload delivery and controlled release.

Main Methods:

• Formation of polyplexes using TAT peptide and pDNA at various nitrogen to phosphate (N/P) ratios.
• Incorporation of alkyl trimethyl ammonium bromide (CnTAB) surfactants to further condense pDNA.
• Characterization of polyplex properties, including size, surface charge, and pDNA encapsulation efficiency.
• Assessment of cytotoxicity and drug loading/release kinetics for doxorubicin and paclitaxel.

Main Results:

• TAT peptide alone formed large carriers with low pDNA immobilization.
• Co-condensation with CnTAB surfactants significantly reduced vector size and improved surface charge and pDNA encapsulation.
• Surfactant chain length critically influenced vector characteristics.
• Cytotoxicity of surfactants was substantially reduced upon complexation.
• Controlled/sustained release of pDNA was achievable, tunable by surfactant chain length and N/P ratio.
• Efficient loading of doxorubicin and paclitaxel into the TAT/pDNA/surfactant carriers was demonstrated.

Conclusions:

• TAT peptide/surfactant complexes offer a promising platform for pDNA delivery.
• This system enhances therapeutic payload encapsulation and enables controlled release.
• The tunable nature of the platform supports innovative biomedical system design for clinical translation.