Interface-targeted drug release driven by photoresponsive polyelectrolyte-surfactant complexes

Using micellar nanocarriers of a photoresponsive arylazopyrazole (AAP) surfactant, the drug release to the air-water interface, as a simple model for an aqueous-hydrophobic interface has been recently demonstrated. In this work, we use a biopolymer poly-l-lysine (PLL) to form surfactant-polyelectrolyte complexes that can enhance the release of the chemotherapeutic drug doxorubicin (Dox). Strong binding between the negatively charged AAP and the positively charged PLL is leading to complexes with a low net charge at equimolar ratios. Combining measurements of the electrophoretic mobility and size of the complexes in the bulk solution with vibrational sum-frequency generation (SFG) spectroscopy of the interface, we determine the optimal PLL concentration that maximizes light-induced drug release to the interface. At PLL/AAP molar ratios >0.9, the complexes exhibit low net charges and a poor colloidal stability, preventing the release of Dox from the bulk solution to the interface. In contrast, at lower PLL/AAP ratios such as 0.5, the system remains colloidally stable due to a significant negative net charge of PLL/AAP complexes, while the release of Dox to the interface is remarkably enhanced and exceeds the release of Dox from AAP micelles in the absence of PLL. This is attributed to the formation of stable PLL/AAP complexes in the bulk solution, which reduce the number of free AAP surfactants and thereby minimize competitive adsorption between free AAP and Dox moieties at the interface. As a result, the adsorption rate of Dox to the air-water interface is accelerated by a factor of ∼6.