Nanoemulsões de nitrosilo complexos de rutênio(II) como moduladores para a entrega de óxido nítrico

Abstract

Nitric oxide (NO) and derivatives are involved in many physiological processes with remarkable importance in vasodilation and inflammation processes. Nitrosyl ruthenium complexes have been studied as an alternative to that along with relevant potential use in the treatment of various pathologies, including cardiovascular disorders. Lipid nanoemulsions could optimize the delivery of these compounds, increasing their stability and bioavailability. Nanoemulsions were prepared with different formulations using as oil phase the oleic acid and Pluronic F-127 or Tween 80 as surfactants, while the metal complex cis- [Ru(bpy)2SO3(NO)]PF6] was employed as a bioactive. Employing 2k factorial design with central point repetition, different formulations were prepared by varying the concentrations of the oil phase and surfactants. Two formulations were selected based on the variables of stability response, hydrodynamic diameter (Dh), polydispersity index (PdI) and zeta potential (ζ). Two formulations were selected for further studies, NanoPlu9 and NanoTw2. Nanoemulsions with the incorporated complex were called NanoPluNO and NanoTwNO. For NanoPluNO, values of Dh = 235.0 ± 6.4 nm, PdI = 0.094 ± 0.022 and ζ = -24.7 ± 0.4 mV were obtained, while NanoTwNO yielded the values Dh = 163.0 ± 2.4 nm, PdI = 0.138 ± 0.010 and ζ = -33.5 ± 0.4 mV. The final complex concentrations in the nanoemulsions were 6.51 mmol L-1 and 2.98 mmol L-1 for NanoPluNO and NanoTwNO, respectively. These nanoemulsions showed interesting values of encapsulation efficiency at 92.6 ± 5.3% and 93.2 ± 8.5% for NanoPluNO and NanoTwNO, respectively. They also behaved as a non-Newtonian pseudo-plastic fluid. The two nanoemulsions showed expressive stability looking at physical parameters during 90 days. Beyond this, the in vitro release of the nitrosyl complex was investigated using an artificial blood plasma (ABP) and under gastric conditions solution as a receptor, whose behavior was quite distinct of a free compound as expected. The profile of the nitrosyl complex release was long lasting within the nanoemulsion following Peppas-Sahlin model for the two nanoemulsions, which indicates an anomalous mass transport by swelling. These interesting behaviors are going to be further explored in biological studies.