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 drugs.Nanoparticles (NP) have emerged as a suitable vehicle able to overcome this kind of absorption barriers. There are a large variety of materials for the preparation of NP. 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. In this work, we used HAS-based NP as vehicle for Timolol Maleato (TM). TM is a nonselective ß-adrenergic receptor antagonist which acts by lowering the intraocular pressure (IOP). It is considered the ﬁrst-line drug for the treatment of glaucoma. The aim of this work was the design and elaboration of nanoparticles coated with Gantrez ES-425® for ocular delivery of TM. Besides, issues concerning the pharmacokinetic (concentration of drug in the aqueous humor) and in vivo efficacy (IOP decreasing) were also studied. Nanoparticles were prepared by a desolvation method, adding absolute ethanol to a solution of HSA, and stabilized with Gantrez ES-425® (0.5 mg/mg HSA). Then, the nanoparticles were puriﬁed by centrifugation and freeze-dried. The physico-chemical characteristics, pharmacokinetic studies and measurement of IOP were performed. The results indicate that NPs had a mean size of 210 nm, a zeta potential of -38.92 mV and a drug loading of 40%. Pharmacokinetics studies showed a maximum concentration of drug 30 min after administration and IOP results showed a maximum reduction in in one hour. In summary, Gantrez?coated HSA nanoparticles displayed adequate physico-chemical characteristics for ophthalmic delivery with high therapeutic effect. Keywords: nanoparticles, ophthalmic delivery, glaucoma, timolol.