CONICET | Buscador de Institutos y Recursos Humanos

Topical ocular application is a common route for drug administration. However, the protective mechanisms of the eye dramatically decrease the bioavailability of drug. Nanoparticles (Nps) have emerged as a suitable vehicle for drugs administration. There are a large variety of materials for the preparation of NPs. Among them, natural biopolymers present more advantages than synthetic materials. In this context, human serum albumin (HSA) offers a number of advantages including its biodegradability and acceptation by Regulatory agencies. The aim of this work was to prepare and evaluate HSA nanoparticles coated with Gantrez ES-425® for ocular delivery of timolol (TM). Nanoparticles were prepared by a desolvation method, adding absolute ethanol to a solution of HSA, and stabilized with either glutaraldehyde (1.5 ug/mg HSA) or Gantrez ES-425® (0.5 mg/mg HSA). Then, the nanoparticles were puriﬁed by centrifugation and freeze-dried. The physico-chemical characteristics and the in-vitro release profiles of the different systems were studied. The results indicate that the interaction between the COO- groups of Gantrez ES-425® and NH3+ of the protein was adequate to stabilize the surface of the nanoparticles. In addition, these nanoparticles displayed a similar stability than NPs cross-linked with glutaraldehyde. Regarding the use of these NPs as carriers for timolol, the nanoparticles stabilized with glutaraldehyde displayed a size of about 160 nm and zeta potential of -35.42 mV with a TM loading of 30%. On the other hand, nanoparticles coated with Gantrez showed a mean size of 210 nm, a zeta potential of -38.92 mV and a drug loading of 40%. In both cases, the in-vitro released profiles showed that after 24 hours, 75% of the TM encapsulated was released. In summary, Gantrez?coated HSA nanoparticles displayed adequate physico-chemical characteristics for ophthalmic delivery and appropriated controlled release properties for the ocular delivery of timolol maleate.