Nanotechnology as a Tool for Optimizing Topical Photoprotective Formulations Containing Buriti Oil (Mauritia flexuosa) and Dry Aloe vera Extracts: Stability and Cytotoxicity Evaluations.

Human beings are actively exposed to ultraviolet (UV) radiation, which is associated with skin cancer. This has encouraged the continuous search for more effective and safer photoprotective formulations. Along with the application of traditional organic sunscreens, there is a growing interest in "green products" containing natural compounds such as plant extracts and oils. This trend is combined with the use of nanotechnology as a tool for optimizing the vehicles of such compounds. Nanoemulsions (NEs) are suitable for the encapsulation of natural compounds, which improves topical treatment. Therefore, we have developed oil-in-water (O/W) nanoemulsions containing 3% buriti oil (BO), incorporated in a 10% vegetal extract of Aloe vera (AV) by means of ultrasonic processing to improve the chemical characteristics of this component and, consequently, its efficacy and safety in pharmaceutical and cosmetic formulations. The composition of the formulation was initially defined in a preliminary study on surfactants where the concentrations of Tween® 80 and Span® 20 were evaluated in relation to particle size and the polydispersity index (PDI). The nanoemulsion was prepared and then chemical sunscreens were incorporated with the aim of developing a sunscreen nanoemulsion called NE-A19. This nanoemulsion was found to be the best formulation due to its stability, droplet size (146.80 ± 2.74), and PDI (0.302 ± 0.088), with a monomodal size distribution. The stability was evaluated over 90 days and showed a low growth in particle size at the end of the study. NE-A19 exhibited good viscosity and organoleptic properties, in addition to an occlusion factor indicating an interesting and higher water holding capacity when compared with a NE without AV (p < 0.05). The in vitro efficacy and safety studies of NE-19A were promising. Its average in vitro sun protection factor value was 49, with a critical wavelength (λc) of 369.7 nm, satisfactory UVA protection, and a UVA/UVB ratio of 0.40, indicating broad spectrum protection against UVA and UVB radiation. Furthermore, NE-19A displayed a good safety profile in dermal keratinocytes. It can be concluded that NE-19A is a promising formulation for carrying natural products, such as buriti oil and AV, associated with synthetic filters in lower concentrations.

Toxicological Effects of Copaiba Oil (Copaifera spp.) and Its Active Components.

Vegetable oils are among the most important traditional resources of Amazonia. Oleoresins are a type of oil that have interesting characteristics and highly bioactive properties with pharmacological potential. Oleoresins produced in the trunks of Copaifera (Fabaceae) spp. trees, known as copaiba oils, are made up of terpenes from the sesquiterpene (volatile) and diterpene (resinous) classes, but in amounts that vary between species and depending on several factors, such as soil type. Despite being used for medicinal purposes, via topical and oral application, the toxic effects of copaiba oils and their constituents are little known. The current paper reviews the toxicological studies, both in vitro and in vivo, described in the literature for copaiba oils, as well as the cytotoxic characteristics (against microorganisms and tumor cells) in in silico, in vitro and in vivo models for the sesquiterpenes and diterpenes that make up these oils.

Development and characterization of a nanoemulsion containing propranolol for topical delivery.

BACKGROUND: Propranolol (PPN) is a therapeutic option for the treatment of infantile hemangiomas. This study aimed at the development of nanoemulsion (NE) containing 1% PPN, characterization of the system, and safety studies based on ex vivo permeation, cytotoxicity, and biodistribution in vivo. METHODS: The formulation was developed and characterized in relation to the droplet size, polydispersity index (PDI), pH, zeta potential, and electronic microscopy. Ex vivo permeation studies were used to evaluate the cutaneous retention of PPN in the epidermis and dermis. Cytotoxicity studies were performed in fibroblasts, macrophages, and keratinocytes. In vivo biodistribution assay of the formulations was performed by means of labeling with technetium-99m. RESULTS: NE1 exhibited droplet size of 26 nm, PDI <0.4, pH compatible with the skin, and zeta potential of -20 mV, which possibly contributes to the stability. Electron microscopy showed that the NE presented droplets of nanometric size and spherical shape. NE1 provided excellent stability for PPN. In the ex vivo cutaneous permeation assay, the NE provided satisfactory PPN retention particularly in the dermis, which is the site of drug action. In addition, NE1 promoted cutaneous permeation of the PPN in small amount. In vivo biodistribution showed that the radiolabeled formulation remained in the skin and a small amount reached the bloodstream. NE1 presented low cytotoxicity to fibroblasts, macrophages, and keratinocytes in the concentrations evaluated in the cytotoxicity assay. CONCLUSION: We concluded that the formulation is safe for skin administration; however, cutaneous irritation studies should be performed to confirm the safety of the formulation before clinical studies in patients with infantile hemangiomas.

Characterization and evaluation of poly(epsilon-caprolactone) nanoparticles containing 2-ethylhexyl-p-methoxycinnamate, octocrylene, and benzophenone-3 in anti-solar preparations.

Ultraviolet radiation can bring both harm and benefits to human health. Among those harms are erythemas, photosensitivity, photoaging, and the most worrying, skin cancer. Nanoencapsulation of sunscreen agents (SA) by using a biocompatible and biodegradable polymer such as poly(epsilon-caprolactone) (PCL) is advantageous as it increases the retention of UV absorbers in the skin, avoids systemic absorption, and consequently, improves water resistance and stability of the preparation. The aim of this work is to develop, characterize, and study the encapsulation of 3 different SA: 2-ethylhexyl-p-methoxycinnamate, benzophenone-3, and octocrylene in PCL nanoparticles (Nps). Nps were prepared by the solvent emulsification and evaporation method. The process yield was calculated, and the Nps were characterized in terms of size, polydispersity index (PI), morphology, zeta potential (ZP), encapsulation efficiency (EE) (%), and sunscreen agent content (SAC). The final formulations were submitted to the hen's egg test-chorioallantoic membrane (HET-CAM), chorioallantoic membrane-trypan blue staining (CAM-TBS), red blood cell (RBC), Draize tests, in vitro release, in vitro sun protection factor (SPF), UVA protection factor (PF-UVA), and photostability. All the Nps were in the nanometric scale. PI showed monodisperse systems. ZP became more negative as the Np were lyophilized and were added to the formulations. EE varied from 84 to 90%. The SAC went from 44 to 65 microg of sunscreen agents by milligram of Np. The process yield went from 60 to 76%. Nps were predominantly spherical and elliptical forms. The addition of Np diminished the release of the SA. The SPF increased with Np presence and helped to maintain the PF-UVA after irradiation. The HET-CAM assay evaluated the formulation as slightly irritant, CAM-TBS and RBC tests as non irritant, and the Draize test as moderately irritant.

Improving the topical delivery of zinc phthalocyanine using oleic acid as a penetration enhancer: in vitro permeation and retention.

Topical photodynamic therapy with zinc phthalocyanine (ZnPc), second-generation photosensitizer, can be an alternative method for the treatment of skin cancer. However, ZnPc has poor penetration in the skin. This study was aimed at investigating whether the presence of oleic acid (chemical enhancer) in propylene glycol can improve the topical delivery of ZnPc. The topical (to the skin) and transdermal (across the skin) delivery of ZnPc were evaluated in vitro using suine ear skin mounted in Franz diffusion cell. Photosensitizer was quantified by fluorescence emission, which is a sensitive and selective method. At 5 and 10%, oleic acid increased the topical and transdermal delivery significantly. When the concentration of oleic acid was further increased (20-60% w/w), the topical delivery of ZnPc was still elevated, but its transdermal delivery was substantially reduced. It was concluded that oleic acid (in propylene glycol formulations) can promote the topical delivery of ZnPc, with reduced transdermal delivery. This approach can be effective for the treatment of skin cancer by topical photodynamic therapy.