SVILUPPO E PROGETTAZIONE DI SISTEMI FOTOATTIVABILI PER TERAPIE OFTALMICHE

The general goal of the research is the design, characterization and potential industrial scale-up of photoactivatable systems including nanoparticles, gels and thin films for innovative ophthalmic therapies. In particular, this project aims to develop innovative constructs incorporating suitable photo-precursors generating nitric oxide (NO) and/or singlet oxygen (1O2) under visible light stimuli. If produced with accurate spatio-temporal control, these species, can act as “unconventional” therapeutics against infections, glaucoma and macular degeneration. In addition, they also offer two great advantages compared to conventional therapeutic agents: i) absence of multidrug resistance and ii) short lifetimes which avoid typical undesired systemic effects. The purpose is to improve the therapeutic efficacy using the photodynamic action of the above transient species through different mechanisms of action either with or without the use of conventional drugs in order to maximize the therapeutic effect and minimize the side effects of drugs. Photons represent an ideal tool in this context as they are easily manipulated in terms of intensity, duration, and wavelength and do not influence the physiological parameters of pH, temperature and ionic strength. Appropriate NO-photodonors (NOPD), activatable by visible light, already developed in the research group, constitute a solid starting point for their suitable modifications to improve the photobehavior and encapsulation capability, in order to develop systems with multimodal therapeutic strategy. The use of prodrugs based on the NOPD can be applied in ophthalmic field, for the antibacterial properties and for the capability of lowering the intraocular pressure (IOP) in glaucoma. This latter is a strategy of increasing interest on the market of ophthalmic drugs for the accurate spatio-temporal control of the NO release and the accessibility of the eye to the light. The photoactivatable systems using designed using already approved FDA polymeric materials and precursors, such us, Pluronics® or cyclodextrin based polymers. The systems will be designed in such a way as to preserve the properties of the components in the nanocarrier, considering the biological barriers that it must overcome to reach the specific target. All systems are characterized in terms of their chemical-physical (shape, size, surface charge), photo-chemical and photo-physical properties (quantum yields of NO and 1O2 release) and biological effects. The development and the combination of new polymers and photo-receptors both offer space for innovation and for the development of new potential photo-nanomedicine.