Mixed protein carriers for modulating DNA release.

Aqueous mixtures of oppositely charged polyelectrolytes undergo associative phase separation, resulting in coacervation, gelation, or precipitation. This phenomenon has been exploited in forming DNA gel particles by interfacial diffusion. We report here the formation of DNA gel particles by mixing solutions of double-stranded DNA with aqueous solutions containing two cationic proteins, lysozyme and protamine sulfate. The effect of the lysozyme/protamine ratio on the degree of DNA entrapment, surface morphology, swelling-deswelling behavior, and kinetics of DNA release has been investigated. By mixing the two proteins, we obtain particles that display higher loading efficiency and loading capacity values, in comparison to those obtained in single-protein systems. Examination of the release profiles has shown that in mixed protein particles, complex, dual-stage release kinetics is obtained. The overall release profile is dependent on the lysozyme/protamine ratio. The obtained profiles, or segments of them, are accuratelly fitted using the zero-order and first-order models, and the Weibull function. Fluorescence microscopy studies have suggested that the formation of these particles is associated with the conservation of the secondary structure of DNA. This study presents a new platform for controlled release of DNA from DNA gel particles formed by interfacial diffusion.