Diosmetin, a novel transient receptor potential vanilloid 1 antagonist, alleviates the UVB radiation-induced skin inflammation in mice.

UVB radiation-mediated inflammation and the oxidative process involve the transient receptor potential vanilloid 1 (TRPV1) channel activation in neuronal and non-neuronal cells. Once diosmetin has been identified as a novel TRPV1 antagonist, we evaluated the action of diosmetin from the inflammatory [ear oedema, myeloperoxidase (MPO) activity, histological changes, and cytokines levels] and oxidative [nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and SOD activities] parameters in mice exposed to UVB radiation (0.5 j/cm2). We also verified the action of diosmetin on UVB radiation-induced inflammatory parameters after cutaneous nerve fibers denervation by RTX (50 µg/kg s.c.). The topical treatment with the novel TRPV1 antagonist, diosmetin (1%; 15 mg/ear), reduced ear oedema, MPO activity, and MIP-2 and IL-1ß cytokines levels by 82 ± 8%, 59 ± 10%, 40 ± 12%, and 85 ± 9%, respectively. The action of diosmetin on ear oedema and inflammatory cell infiltration was histologically confirmed. Topical diosmetin (1%) also reduced NADPH oxidase activity by 67 ± 10% and reverted SOD activity by 81 ± 13%. After cutaneous nerve fibers denervation using RTX, diosmetin reduced ear oedema, but not the inflammatory cell infiltration in mice exposed to UVB radiation. Diosmetin can be a promising molecule against skin inflammatory disorders as a result of sunburn induced by UVB radiation exposure.

Neuronal and non-neuronal transient receptor potential ankyrin 1 mediates UVB radiation-induced skin inflammation in mice.

AIMS: Neuronal and non-neuronal TRPA1 channel plays an active role in the pathogenesis of several skin inflammatory diseases. Although a recent study identified the TRPA1 channel activation upon UVB exposure, its role in inflammatory, oxidative, and proliferative processes underlying UVB radiation-induced sunburn was not yet fully understood. We evaluated the TRPA1 channel contribution in inflammatory, oxidative, and proliferative states on skin inflammation induced by UVB radiation in mice. MAIN METHODS: TRPA1 role was evaluated from inflammatory (ear edema, myeloperoxidase, and N-acetyl-ß-D-glycosaminidase activities, histological changes, and cytokines levels), proliferative (epidermal hyperplasia, PCNA, and TRPA1 levels), and oxidative (reactive oxygen intermediates measure, H2O2 quantification, and NADPH oxidase activity) parameters caused by UVB radiation single (0.5 J/cm2) or repeated (0.1 J/cm2) exposure. We verified the contribution of non-neuronal and neuronal TRPA1 on UVB radiation-induced inflammatory parameters using RTX-denervation (50 µg/kg s.c.). KEY FINDINGS: TRPA1 blockade by the selective antagonist Lanette® N HC-030031 reduced all parameters induced by UVB radiation single (at concentration of 1%) or repeated (at concentration of 0.1%) exposure. We evidenced an up-regulation of the TRPA1 protein after UVB radiation repeated exposure, which was blocked by topical Lanette® N HC-030031 (0.1%). By RTX-denervation, we verified that non-neuronal TRPA1 also interferes in some inflammatory parameters induction. However, cutaneous nerve fibers seem to be most needed in the development of UVB radiation-induced inflammatory processes. SIGNIFICANCE: We propose the TRPA1 channel participates in the UVB radiation-induced sunburn in mice, and it could be a promising therapeutic target to treat skin inflammatory disorders.

Improved photostability and cytotoxic effect of coenzyme Q10 by its association with vitamin E acetate in polymeric nanocapsules.

The present study showed the development of nanocapsules containing the association of the coenzyme Q10 and vitamin E acetate and the evaluation of their effect on in vitro cells culture of malignant glioma and melanoma. In order to investigate if nanocapsules are able to protect coenzyme Q10 from degradation under UVC radiation, a photostability study was carried out. For this, three concentrations of vitamin E acetate were evaluated (1%, 2%, or 3%). Nanocapsules presented suitable physicochemical characteristics and were able to protect coenzyme Q10 from photodegradation. In addition, this protection was influenced by higher vitamin E acetate concentrations, attributing to this oil an important role on coenzyme Q10 photostabilization. Regarding to in vitro citotoxicity assay, nanocapsules containing coenzyme Q10 and 2% vitamin E significantly reduced glioma and melanoma cell viability in 61% and 66%, respectively. In this sense, these formulations represent interesting platforms for the delivery of coenzyme Q10 and vitamin E acetate, presenting effect on the reduction of malignant cells viability.

Nanoencapsulation of coenzyme Q10 and vitamin E acetate protects against UVB radiation-induced skin injury in mice.

This study aimed to investigate the feasibility of producing semisolid formulations based on nanocapsule suspensions containing the association of the coenzyme Q10 and vitamin E acetate by adding gellan gum (2%) to the suspensions. Furthermore, we studied their application as an alternative for the treatment of inflammation induced by ultraviolet B (UVB) radiation. For this, an animal model of injury induced by UVB-radiation was employed. All semisolids presented pH close to 5.5, drug content above 95% and mean diameter on the nanometric range, after redispersion in water. Besides, the semisolids presented non-Newtonian flow with pseudoplastic behavior and suitable spreadability factor values. The results also showed that the semisolid containing coenzyme Q10-loaded nanocapsules with higher vitamin E acetate concentration reduced in 73±8% the UVB radiation-induced ear edema. Moreover, all formulations tested were able to reduce inflammation parameters evaluated through MPO activity and histological procedure on injured tissue and the semisolids containing the nanoencapsulated coenzyme Q10 reduced oxidative parameters assessment through the non-protein thiols levels and lipid peroxidation. This way, the semisolids based on nanocapsules may be considered a promising approach for the treatment and prevention of skin inflammation diseases.

Formulation and in vitro evaluation of coconut oil-core cationic nanocapsules intended for vaginal delivery of clotrimazole.

The objective of this work was to propose coconut oil-core nanocapsules prepared from Eudragit(®) RS100, a cationic polymer, and to evaluate their potential for vaginal delivery of clotrimazole in candidiasis. Nanocapsule suspensions loaded with clotrimazole at 1.0 and 3.0mg/mL were prepared by interfacial deposition of Eudragit(®) RS100. The physicochemical characterization showed average diameter lower than 200 nm, low polydispersity index, positive zeta potential (+10.94 to +14.57 mV), acid pH values (5.4-5.7) and encapsulation efficiencies close to 100%. After 60 days of storage at room temperature and protected from light, the nanocapsules were reasonably stable. Photodegradation studies showed that nanoencapsulation improved clotrimazole stability against UV radiation. The in vitro drug release at pH 4.5 was characterized by a prolonged release with no burst effect. The nanocapsules were more active than free clotrimazole against Candida albicans and Candida glabrata strains susceptible and resistant to fluconazole. Hence, clotrimazole-loaded coconut oil-core nanocapsules represent promising alternatives to the treatment of vulvovaginal candidiasis.