Sabrina Sepulveda Rivas
Universidad de Chile
My name is Sabrina Sepúlveda Rivas, Medical Technology and PhD (C) in Pharmacology with focus in cardiovascular nanomedicine at the University of Chile.
During my PhD I develop an effective drug delivery system that can transport and controlled drug release. Also I evaluate the influence of our recently developed Eudragit E-alginate (EE-Alg) nanoparticles on cell viability and cell morphology. Then, I investigate the colloidal stability and the release profiles of a peptide with excellent properties for cardiovascular therapy. In order to increase our understanding of its potential biomedical applications.
Introduction
Angiotensin-(1-9) has been reported as a peptide of renin-angiotensin system (RAS) and a novel anti-cardiac hypertrophy agent (1). The clinical application of Angiotensin-(1-9) is restricted due to its pharmacokinetic properties including a short half-life in vivo attributed to enzymatic metabolism. Nanoparticles are promising vehicles that can provide protection, controlled drug release, improving bioavailability, and transport of numerous bioactive molecules (2). The aim of this study was to prepare nanohybrids as a carrier system for angiotensin-(1-9), and then to investigate the colloidal stability and the release profiles.
Methods
Nanohybrids which consists in the mixture of Eudragit E (EE), Alginate (Alg), gold nanoparticles (AuNPs) and Angiotensin-(1-9) (EE/Alg/AuNPs/Ang-(1-9)) were obtained by coacervation of aqueous EE (polycation) and Alg (polyanion) solutions and then loaded with gold nanoparticles and angiotensin-(1-9). Controlling the amounts of charges in play during the coacervation process, we evaluated negatively charged systems. Size, polydispersity index and zeta potential of nanohybrids were characterized by dynamic light scattering and laser Doppler electrophoresis in a Zetasizer Nano ZS. Nanoparticle tracking analysis (NTA) were performed using a NanoSight NS300 instrument. The stability parameters were studied at different temperatures (room temperature or 37°C), media (phosphate buffer pH 7.4, DMEM/M199 and plasma) and time. For determining encapsulation efficiency and in vitro drug release, angiotensin-(1-9) was quantified by HPLC Flexar (Perkin Elmer) detecting at a 220 nm wavelength.
Results
All studied conditions allowed the formation of nanohybrids by coacervation of [EE/Alg/AuNPs/Ang-(1-9)]. Hydrodynamic diameters and zeta potential of nanohybrids were media, temperature and time. Nanohybrids showed high encapsulation efficiencies (>68%), providing further evidence of the high affinity of the nanocarriers for the encapsulated peptide. Release studies showed a rapid release of the peptide during the first minutes, 75% after 15 minutes and the release was 100% at 105 minutes. These results provide evidence of the capacity of these nanohybrids, which could act as a protective vehicle for this peptide.
Discussion
Overall, these data suggest that the nanohybrids developed are promising nanocarriers for the delivery of angiotensin-(1-9), providing the insights of the application of nanohybrids as delivery systems of angiotensin-(1-9) for cardiovascular therapy.
