The present work reports a nanotechnology strategy to prepare a low-viscosity poly(acrylic acid) (PAAc)-based tear substitute with enhanced efficacy and compliance. Specifically, nanogels composed of PAAc and polyvinylpyrrolidone (PVP) were prepared by adapting an ionizing radiation method. For this purpose, different aqueous systems: PVP/PAAc nanoparticulate complexes, PVP/acrylic acid (AAc), N-vinylpyrrolidone (N-VP)/PAAc, and N-VP/AAc were exposed to gamma rays. The dynamic light scattering technique showed that stable nanogels are only produced in a relatively high yield from the PVP/AAc system. Nanogel formation was driven by the hydrogen-bonding complexation between PVP and PAAc (formed in situ) as well as the radiation-induced cross-linking. Transparency, viscosity and mucoadhesiveness of emerged nanogels were optimized by controlling the feed composition and irradiation dose. Furthermore, neutralized nanogels were topically applied in a dry eye model and compared with a PAAc-based commercial tear substitute, namely Vidisic® Gel. The results of Schirmer's test and tear break-up time demonstrated that nanogels prepared from AAc-rich feed solutions at 20 kGy enhanced markedly the dry eye conditions. The histopathological analysis also ensured the competence of PAAc-rich nanogels to completely return the corneal epithelium to its normal state.
Keywords: Dry eye; Gamma rays; Mucoadhesion; Nanogel; Poly(acrylic acid); Tear substitute.
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