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

Abstract

The development of delivery systems based on cell penetrating peptides represents an incredible asset and may deeply contribute for the evolution of therapies efficacy. In this context, we explore the plasmid DNA (pDNA) condensation ability of TAT peptide to produce a suitable intracellular delivery platform. The nanoparticles were formed at various ratios of nitrogen to phosphate groups (N/P) and the variation of polyplexes properties with this parameter was studied. Beyond the large size exhibited by these carriers, their low pDNA immobilization profile instigates the need for an additional compacting agent. To maximize the performance of this peptide delivery system, a series of alkyl trimethyl ammonium bromide surfactants (CnTAB) were employed to further condense pDNA. In general, not only this strategy promotes the formation of lower sized vectors, but also greatly enhances particle characteristics such as surface charge and pDNA encapsulation. The magnitude of this effect is intimately dependent on surfactant chain length. Furthermore, the known cytotoxicity of cationic surfactants has been dramatically reduced by their incorporation into TAT/pDNA complexes. The release kinetics can be tailored and optimized to promote the controlled/sustained release of pDNA. Following this, the surfactant alkyl chain length and the N/P ratio are important controlling parameters. In addition, doxorubicin and paclitaxel can be efficiently loaded and encapsulated into peptide/pDNA/surfactant carriers. The presented platform reveals a great potential for therapeutic payloads loading and controlled release open advanced and new approaches in the design/formulation of innovative biomedical systems towards clinical translation.