Specific Loading and in Vitro Controlled Release of a Ru-Based Hydrophobically Encapsulated Model Anticancer Drug inside Nanoassemblies toward Stimuli-Responsive Drug Delivery

Abstract

Stimuli-responsive water-dispersible and structurally robust nanoassemblies find tremendous importance in the biomedical domain for delivery of therapeutically active hydrophobic drugs and bioimaging applications. Herein we have demonstrated the loading of a hydrophobic model anticancer drug, [(p-cymene)Ru(curcuminato)Cl] (Ru-Cur), inside hydrophobic compartments of different nanoassemblies, namely, micelles, liposomes, and coacervate nanodroplets, and studied the in vitro pH- and temperature-dependent controlled-release profiles. In the present study, both carbon-dot and adenosine triphosphate (ATP)-based coacervate nanodroplets have been fabricated in the presence of poly(diallyldimethylammonium chloride) (PDADMAC). It has been observed that the coacervate nanodroplets provide an ideal microenvironment for efficient loading (loading content = 31.2%, and encapsulation efficiency = 99.6%) and sustained release of the hydrophobic drug. The tailorability in the structure and physicochemical properties of coacervate nanodroplets along with high drug loading and negligible drug leakage at physiological conditions makes them ideal nanocarriers over other conventional nanoassemblies. Experimental release profiles for Ru-Cur-loaded ATP nanodroplets at different pH values fit well with a semiempirical power law model. The fitted parameters reveal diffusion- and swelling-controlled-release mechanism in the pH range between 7.4 and 6 and diffusion- and erosion-controlled-release mechanism at pH 5. Moreover, it has been found that the temperature has a profound influence on the drug-release profiles. The present study provides fundamental insight into the pH-responsive disassembly mechanism and highlights the potential importance of these Ru-Cur-loaded coacervates toward various theranostic applications. ©