Design and in vitro characterization of a novel melatonin delivery system

IMPERIALE J.C.; ACOSTA G.; SOSNIK, A.

Congreso; Reunión Conjunta de sociedades de biociencias.; 2017

Reunión Conjunta de sociedades de biociencias.

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. These disadvantages can be approached through the encapsulation of the drug in muco-adhesive polymeric nanoparticles in form of solution that enhances melatonin stability and prolongs the residence time. Melatonin loaded Eudragit® RLPO nanoparticles were produced by nanoprecipitation technique using acetone as solvent. It was effectively extracted as was confirmed by gas chromatography. The hydrodynamic diameter, determined by dynamic light scattering, ranged from 10 to 100 nm with polydispersity index of 0.118 ± 0.005 and Zeta potential of 54.7 ± 1.8 mV. The high value of Zeta potential predicts the physical colloidal stability. In fact, nanoparticles maintained its size and superficial charge for two months. Transmission electron microscopy evidenced the spherical morphology of nanoparticles. The encapsulation efficiency was close to 100%, as determined by UV-Vis spectrophotometry (λ = 278 nm). The muco-adhesiveness was characterized by mucin solution method showing a significant increase in size after incubation in mucin solution and a significant reduction in Zeta potential. To sum up, we have successfully developed a novel melatonin delivery system with potential advantages to be administered in solution form that enable to cover pediatric and adult treatments. Remarkably, its muco-adhesive properties would permit to prolong the residence time and therefore bioavailability and duration of action.