Design and in vitro characterization of a novel melatonin delivery system.

IMPERIALE, JULIETA C.; A SOSNICK; ACOSTA GB

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias.; 2017

SAFE, SAIC, SAI, SAFIS,

DESIGN AND IN VITRO CHARACTERIZATION OF A NOVEL MELATONIN DELIVERY SYSTEM Melatonin is a hormone used for treating circadian rhythm disorders such as jet-lag and insomnia. Also, it has shown anti-tumoral properties on various types of cancers and neuroprotective effects in diseases like Alzheimer and glaucoma. Although it belongs to Class 1 according to the Biopharmaceutical Classification System (high permeability, high solubility), melatonin has low bioavailability (≈15%) due to an extensive hepatic first pass. Furthermore, it exhibits a low dissolution rate and stability problems in aqueous solutions. We hypothesize that these biopharmaceutical disadvantages can be approached through the encapsulation of the drug in muco-adhesive polymeric nanoparticles that undergo intestinal absorption or by their localized administration. In this work, we present the encapsulation of melatonin in Eudragit® RLPO nanoparticles by a nanoprecipitation technique using acetone as solvent. The hydrodynamic diameter, determined by dynamic light scattering (DLS), ranged from 10 to 100 nm with polydispersity index of 0.118 ± 0.005 and zeta-potential of +54.7 ± +1.8 mV due to the polycationic nature of the polymeric carrier. The high value of zeta- potential predicts good physical stability. In fact, nanoparticles maintained their size and superficial charge for at least two months. Transmission electron microscopy evidenced the spherical morphology of nanoparticles. The encapsulation efficiency was approximately 100%, as determined by UV-Vis spectrophotometry (λ = 278 nm). The muco-adhesiveness in vitro was characterized by mucin solution method by DLS where a significant increase in size and a significant reduction in zeta-potential were observed. Overall, these preliminary results suggest that a platform of melatonin-loaded nanoparticles could be capitalized to improve the delivery of this active molecule by a variety of mucosal routes. Keywords: Melatonin, nanoparticles, improved delivery