Dermal quercetin lipid nanocapsules: Influence of the formulation on antioxidant activity and cellular protection against hydrogen peroxide.

Quercetin is a plant flavonoid with strong antioxidant and antiinflammatory properties interesting for skin protection. However, its poor water solubility limits its penetration and so its efficiency on skin. For this purpose, quercetin lipid nanocapsules were formulated implementing phase inversion technique wherein several modifications were introduced to enhance quercetin loading. Quercetin lipid nanocapsules were formulated with two particle size range, (50nm and 20nm) allowing a drug loading of 18.6 and 32mM respectively. The successful encapsulation of quercetin within lipid nanocapsules increased its apparent water solubility by more than 5000 fold (from 0.5µg/ml to about 5mg/ml). The physicochemical properties of these formulations such as surface charge, stability and morphology were characterized. Lipid nanocapsules had spherical shape and were stable for 28days at 25°C. Quercetin release from lipid nanocapsules was studied and revealed a prolonged release kinetics during 24h. Using DPPH assay, we demonstrated that the formulation process of lipid nanocapsules did not modify the antioxidant activity of quercetin in vitro (92.3%). With the goal of a future dermal application, quercetin lipid nanocapsules were applied to THP-1 monocytes and proved the cellular safety of the formulation up to 2µg/ml of quercetin. Finally, formulated quercetin was as efficient as the crude form in the protection of THP-1 cells from oxidative stress by exogenous hydrogen peroxide. With its lipophilic nature and occlusive effect on skin, lipid nanocapsules present a promising strategy to deliver quercetin to skin tissue and can be of value for other poorly water soluble drug candidates.

Ocular toxicity in low-dose tamoxifen: a prospective study.

PURPOSE: To look at the incidence, symptomatology, course and reversibility of low-dose tamoxifen ocular toxicity. METHODS: Sixty-five women with breast cancer, on tamoxifen oral therapy (20 mg/day), and a totally normal eye examination, were prospectively followed up. A full ophthalmic evaluation was done every 6 months, for a median of 30 months (range 4-79 months). Any sign of toxicity in the cornea, lens, retina or optic nerve was looked for, whether associated with a change in visual acuity or not. RESULTS: Ocular toxicity was documented in 8 patients, giving an incidence of 12%. Seven patients had keratopathy in the form of subepithelial deposits, whorls and linear opacities. Three of these patients had a concurrent symptomatic bilateral pigmentary retinopathy that warranted discontinuation of therapy. One patient developed bilateral optic neuritis that left her with optic nerve pallor and a decrease in vision. The patients who had the toxicity had a significantly higher tamoxifen cumulative dose (p = 0.03), and were longer on treatment (p = 0.04), than the non-affected ones. The keratopathy changes were reversible upon discontinuation of the drug. CONCLUSION: Prompt reporting of symptoms and yearly ophthalmic examinations are mandatory in patients on tamoxifen to detect toxic effects while these are still reversible.