Preparation and in vitro evaluation of topical formulations based on polystyrene-poly-2-hydroxyl methacrylate...

The skin disposition of topically applied nanoparticles with varying degrees of hydrophobicity, composed of different proportions of polystyrene (PS) and poly-(2-hydroxyethyl methacrylate) (HEMA), and of an associated, model "active" (Nile Red), was investigated. PS-HEMA copolymer nanoparticles were fluorescently labeled, via the covalent incorporation of a small quantity of fluorescein methacrylate, and characterized by dynamic light scattering, transmission electron microscopy and NMR. The fluorophore, Nile Red, was dispersed into the nanoparticles and its loading was determined by ultracentrifugation. Skin uptake was assessed in vitro following a 6 h application of the nanoparticle formulation, via stratum corneum (SC) tape-stripping and confocal microscopy. Nanoparticle diameters were below 100 nm. Progressive introduction of HEMA decreased particle hydrophobicity and reduced Nile Red loading. Uptake of Nile Red into the skin, as assessed both by the amounts extracted from the SC and by confocal microscopy, decreased as the percentage HEMA increased. Confocal microscopy confirmed that nanoparticles could not move beyond the superficial SC, but did show affinity for hair follicle openings. In conclusion, the loading of a lipophilic "active" into nanoparticles, and its subsequent release when these formulations are applied topically, are sensitive to the composition and relative hydrophobicity of the carrier.