Pullulan film incorporated with nanocapsules improves pomegranate seed oil anti-inflammatory and antioxidant effects in the treatment of atopic dermatitis in mice.

This study aimed to prepare pullulan films containing pomegranate seeds oil (PSO) based nanocapsules, and evaluate the formulation efficacy in the treatment of atopic dermatitis (AD)-like lesions induced by 2,4-dinitrochlorobenzene (DNCB). The Eudragit RS 100® nanocapsules (PSONC) were prepared by the interfacial precipitation of preformed polymer, whereas the films were produced by the solvent casting method. Pomegranate seed oil nanoemulsions (PSONE) were prepared by the spontaneous emulsification method for comparative reasons. Both nanosystems presented adequate mean diameter (248 ± 16 nm for PSONE and 181 ± 6 nm for PSONC), polydispersity index (below 0.2), zeta potential (-25.63 ± 1.1 mV for PSONE and + 43.13 ± 0.7 mV for PSONC) and pH in the acid range (6.77 ± 0.27 and 5.31 ± 0.17, PSONE and PSONC). By a pre-formulation study, sorbitol (6.5%) and PEG 400 (1.5%) were considered the most suitable plasticizers for developing pullulan films (6%) intending topical application. In general, pullulan films were classified as flexible and hydrophilic, with high occlusive properties, 57.6 ± 0.8%, 64.6 ± 0.8% for vehicle, PSONCF (pullulan film containing PSONC), respectively. All formulations (films and nanocarriers) presented no irritant potential in the chorioallantoic membrane test. In the in vivo model, the treatments with free PSO and PSONCF attenuated the skin injury as well as the mechanical hypernociceptive behavioral induced by DNCB exposure to mice. Importantly, the biochemical analyses provided evidence that only the treatment with PSONCF modulated the inflammatory and the oxidative stress parameters evaluated in this study. In conclusion, these data lead us to believe that PSONC incorporation into a pullulan film matrix improved the biological properties of the PSO in this AD-model.

Pomegranate seed oil nanoemulsions with selective antiglioma activity: optimization and evaluation of cytotoxicity, genotoxicity and oxidative effects on mononuclear cells.

CONTEXT: Glioma is a malignant brain tumor with rapid proliferation, infiltrative growth, poor prognosis and it is chemoresistent. Pomegranate seed oil (PSO) has antioxidant, anti-inflammatory and antitumor properties. This study showed the optimization of PSO nanoemulsions (NEs) as an alternative for glioma treatment. OBJECTIVE: The study aimed to evaluate PSO NEs cytotoxicity on human blood cells and antiglioma effects against C6 cells. MATERIALS AND METHODS: NEs were prepared by the spontaneous emulsification method, using PSO at 1.5 and 3.0%, and were evaluated regarding their physical stability and antioxidant activity. Toxicity evaluations in human blood cells were performed in terms of cell viability, genotoxicity, lipid peroxidation, protein carbonylation, catalase activity and hemolysis at 0.1, 0.25 and 0.5 mg/mL PSO, after a 72-h incubation period. In vitro antitumor effect was determined against glioma cells after 24 and 48 h, and astrocytes were used as a non-transformed cell model. RESULTS: Formulations presented droplet size below 250 nm, low polydispersity index, negative zeta potential and pH in the acid range. NEs and PSO had scavenging capacity around 30% and promoted a proliferative effect in mononuclear cells, increasing about 50% cell viability. No genotoxic and oxidative damage was observed in lipid peroxidation, protein carbonylation and catalase activity evaluations for NEs. Hemolysis study showed a hemolytic effect at high concentrations. Moreover, formulations reduced only tumor cell viability to 47%, approximately. DISCUSSION AND CONCLUSION: Formulations are adequate and safe for intravenous administration. Besides, in vitro antitumor activity indicates that NEs are promising for glioma treatment.