Development of melatonin-loaded, human-serum-albumin nanoparticles formulations using different methods of preparation for ophthalmic administration

Abstract

The use of proteins such as human serum albumin (HSA) to form nanometric systems seems very promising since they are non-toxic, biodegradable and have no antigenic activity. This molecule is ideal to transport insoluble drugs such as melatonin (Mel), which has antiapoptotic and antioxidant properties and appears promising for the treatment of neurodegenerative eye diseases. The objective of this study was to obtain nanoparticulate systems loaded with Mel, improving the conventional desolvation method. Systems were stabilised using two different strategies: one through the use of Eudragit S100 as a cross-linking agent and the other through thermal stabilisation. The systems thus obtained (Np-HSA-Eu-Mel and Np-HSA-Mel, respectively) were characterised and compared in terms of physicochemical and pharmacotechnical parameters. Whitish colloidal dispersions of nanometric size (≈170 nm), spherical shape, and monodisperse population were obtained. Besides, the pH was close to neutrality reaching 20 % drug encapsulation whereas the process performance was higher than 80 %. In FT-IR studies, thermal analysis and X-ray diffraction (XRD), the incorporation of the drug in the cavities of the nanoparticles could be evidenced. Regarding the physical stability of nanoparticles, for Np-HSA-Eu-Mel instability was observed at pH > 7. However, Np-HSA-Mel was able to remain stable at different pH levels. Mel release from these systems was consequently affected, where the former released faster than the active compared to the last. On the other hand, it was observed that the drying process (lyophilization in this case) applied to the nanoparticles suspensions does not affect their original properties after redispersion over a three months period. Likewise, the formulation did not produce irritation when administered topically, whereas when administered subconjunctivally, only slight irritation was observed 24 h after administration. According to the result of this study, the Np-HSA-Mel formulation could achieve advantageous properties as a vehicle for the transport of insoluble drugs for the treatment of neurodegenerative diseases at the ocular level.