Delivery of antiangiogenic and antioxidant drugs of ophthalmicinterest through a nanoporous inorganic filter

[摘要] Purpose: We propose a novel method of administration ofantiangiogenic and antioxidant drugs, with potential clinicalapplication in the treatment of proliferative diabetic retinopathy (PDR)and age-related macular degeneration (AMD). We suggest the encapsulationof drugs in implantable sustained release devices, limited by membraneswith pores in the tens of nanometers diameter range, which display aslower, quasi-linear release kinetics, and a better selectivity thanother membranes. In this paper we explored the feasibility of thisapproach by testing in vitro several key elements of the nanofiltersystem: diffusion of drugs of interest, efficacy in producing desirableeffects on cells, and biocompatibility of used material with some of thecells encountered in the ocular cavity.Methods: We used an aluminum oxide filter (AnoporeTM) with pores of20 nm as a limiting medium for the administration of drugs. First, weinduced an oxidative stress in human retinal endothelial cells (HREC) bytreating them with hydrogen peroxide diffused across the filter, in theabsence or in the presence of catalase. HREC attached to the cultureplate, or emerging as angiogenic sprouts from aggregates embedded incollagen gels, were also exposed to vitamin C or to endostatin deliveredacross the nanoporous filter. Direct exposure of the cells to the agentsserved as positive controls. Growth of cells on the filter wasconsidered an indication for biocompatibility.Results: Catalase diffused across the nanoporous membranecounteracted the cytotoxic effect of hydrogen peroxide on HREC. We alsofound that vitamin C, acting directly or after diffusion across thefilter, up to concentrations physiologically present in the eye, was aconcentration dependent modulator of HREC's ability to survive andsprout. Additionally, we confirmed the ability of endostatin to blockthe growth of HREC either attached or sprouting from cell aggregates,after diffusion across the AnoporeTM nanofilter.Conclusions: The drug delivery method based on the administration ofangiostatic and antioxidant agents across the inorganic aluminum oxidenanoporous filter passed the key in vitro tests for diffusibility andbiocompatibility, opening the way for medical applications.

[学科分类] 生物化学/生物物理