Improvement in Solubility-Permeability Interplay of Psoralens from Brosimum gaudichaudii Plant Extract upon Complexation with Hydroxypropyl-ß-cyclodextrin.

Psoralen (PSO) and 5-methoxypsoralen (5-MOP) are widely used drugs in oral photochemotherapy against vitiligo and major bioactive components of root bark extract of Brosimum gaudichaudii Trécul (EBGT), previously standardized by LC-MS. However, the exceptionally low water solubility of these psoralens can cause incomplete and variable bioavailability limiting their applications and patient adherence to treatment. Therefore, the purpose of this work was to investigate the effects of 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) inclusion complex on the solubility and jejunal permeability of PSO and 5-MOP from EBGT. Characterization of inclusion complexes were evaluated by current methods in nuclear magnetic resonance studies on aqueous solution, Fourier transform infrared spectroscopy, thermal analysis, and scanning electron microscopy in solid state. Ex vivo rat jejunal permeability was also investigated and compared for both pure psoralens and plant extract formulation over a wide HP-ß-CD concentration range (2.5 to 70 mM). Phase solubility studies of the PSO- and 5-MOP-HP-ß-CD inclusion complex showed 1:1 inclusion complex formation with small stability constants (Kc < 500 M−1). PSO and 5-MOP permeability rate decreased after adding HP-ß-CD by 6- and 4-fold for pure standards and EBGT markers, respectively. Nevertheless, the complexation with HP-ß-CD significantly improved solubility of PSO (until 10-fold) and 5-MOP (until 31-fold). As a result, the permeability drop could be overcome by solubility augmentation, implying that the HP-ß-CD inclusion complexes with PSO, 5-MOP, or EBGT can be a valuable tool for designing and developing novel oral drug product formulation containing these psoralens for the treatment of vitiligo.

Efficacy of nanoemulsion with Pterodon emarginatus Vogel oleoresin for topical treatment of cutaneous leishmaniasis.

Cutaneous leishmaniasis (CL) is a neglected tropical skin disease caused by the protozoan genus Leishmania. The treatment is restricted to a handful number of drugs that exhibit toxic effects, limited efficacy, and drug resistance. Additionally, developing an effective topical treatment is still an enormous unmet medical challenge. Natural oils, e.g. the oleoresin from P. emarginatus fruits (SO), contain various bioactive molecules, especially terpenoid compounds such as diterpenes and sesquiterpenes. However, its use in topical formulations can be impaired due to the natural barrier of the skin for low water solubility compounds. Nanoemulsions (NE) are drug delivery systems able to increase penetration of lipophilic compounds throughout the skin, improving their topical effect. In this context, we propose the use of SO-containing NE (SO-NE) for CL treatment. The SO-NE was produced by a low energy method and presented suitable physicochemical characteristic: average diameter and polydispersity index lower than 180 nm and 0.2, respectively. Leishmania (Leishmania) amazonensis-infected BALB/c mice were given topical doses of SO or SO-NE. The topical use of a combination of SO-NE and intraperitoneal meglumine antimoniate reduced lesion size by 41 % and tissue regeneration was proven by histopathological analyses. In addition, a reduction in the parasitic load and decreased in the level of IFN-γ in the lesion may be associated, as well as a lower level of the cytokine IL-10 may be associated with a less intense inflammatory process. The present study suggests that SO-NE in combination meglumine antimoniate represents a promising alternative for the topical treatment of CL caused by L. (L.) amazonensis.

Is it possible to obtain nanodispersions with jaboticaba peel's extract using low energy methods and absence of any high cost equipment?

Jaboticaba (Myrciaria cauliflora) is considered a "super fruit" due to its remarkable phenolic content and antioxidant capacity. Despite the great potential of its peels, to our knowledge the investigation of novel nanostructured systems with this natural raw material, still considered an industrial residue, is scarce. The present study aimed to obtain nanodispersions with its peel's extract through a low energy method. Antioxidant assays were performed, showing positive results for DPPH (IC50 = 0.89 µg/mL) and FRAP (225.53 µmol equivalent ferrous sulphate/g). The chemical characterization in terms of flavonoids (2.56%) and total monomeric anthocyanins (0.80%) contents were also performed. Overall, the nanodispersion prepared with the non-ionic surfactant polysorbate 85 and the hydroalcoholic extract standardized in ellagic acid (129 µg/mL) presented the best properties regarding particle size distribution and zeta potential. Thus, it opens perspectives for the generation of novel food-grade nanodispersions through an ecofriendly approach that is in accordance to sustainable concepts.

Pterodon emarginatus oleoresin-based nanoemulsion as a promising tool for Culex quinquefasciatus (Diptera: Culicidae) control.

BACKGROUND: Preparation of nanoformulations using natural products as bioactive substances is considered very promising for innovative larvicidal agents. On this context, oil in water nanoemulsions develop a main role, since they satisfactorily disperse poor-water soluble substances, such as herbal oils, in aqueous media. Pterodon emarginatus, popularly known as sucupira, has a promising bioactive oleoresin. However, to our knowledge, no previous studies were carried out to evaluate its potential against Culex quinquefasciatus, the main vector of the tropical neglected disease called lymphatic filariasis or elephantiasis. Thus, we aimed to investigate influence of different pairs of surfactants in nanoemulsion formation and investigate if a sucupira oleoresin-based nanoemulsion has promising larvicidal activity against this C. quinquefasciatus. We also evaluated morphological alteration, possible mechanism of insecticidal action and ecotoxicity of the nanoemulsion against a non-target organism. RESULTS: Among the different pairs of surfactants that were tested, nanoemulsions obtained with polysorbate 80/sorbitan monooleate and polysorbate 80/sorbitan trioleate presented smallest mean droplet size just afterwards preparation, respectively 151.0 ± 2.252 and 160.7 ± 1.493 nm. They presented high negative zeta potential values, low polydispersity index (<0.300) and did not present great alteration in mean droplet size and polydispersity index after 1 day of preparation. Overall, nanoemulsion prepared with polysorbate 80/sorbitan monooleate was considered more stable and was chosen for biological assays. It presented low LC50 value against larvae (34.75; 7.31-51.86 mg/L) after 48 h of treatment and some morphological alteration was observed. The nanoemulsion did not inhibit acetylcholinesterase of C. quinquefasciatus larvae. It was not toxic to green algae Chlorella vulgaris at low concentration (25 mg/L). CONCLUSIONS: Our results suggest that optimal nanoemulsions may be prepared with different surfactants using a low cost and low energy simple method. Moreover, this prototype proved to be effective against C. quinquefasciatus, being considered an ecofriendly novel nanoproduct that can be useful in integrated control programs of vector control.

Multiresponse optimization of an extraction procedure of carnosol and rosmarinic and carnosic acids from rosemary.

A green solvent-based optimization for rosmarinic acid (RA), carnosol (COH), and carnosic acid (CA) extraction, the three main antioxidants from rosemary, was performed. The conventional solid-liquid extraction was optimized using a central composite design (CCD) followed by the desirability approach. In the CCD analysis the quantitative effects of extraction time (4.8-55.2min), liquid-to-solid ratio (4.6-21.4mLg(-1)), and ethanol content (44.8-95.2% v/v) were determined for the extracted amount of antioxidants, their concentrations in the extract, and the extraction yield. Samples were analyzed by HPLC and the antioxidants were identified by comparison with pure standard retention times and UV spectra. The desirability function that simultaneously maximizes the antioxidants extraction and their concentrations in the final product was validated. The extraction using a hydroalcoholic solution 70% v/v, at low liquid-to-solid ratio (5mLg(-1)), and after 55-min yielded an antioxidant recovery rate of 89.8%, and a final product 4.75 times richer in the main antioxidants than the raw material.

Development of a Larvicidal Nanoemulsion with Pterodon emarginatus Vogel Oil.

Pterodon emarginatus Vogel is a Brazilian species that belongs to the family Fabaceae, popularly known as sucupira. Its oil has several biological activities, including potent larvicidal property against Aedes aegypti. This insect is the vector of dengue, a tropical disease that has been considered a critical health problem in developing countries, such as Brazil. Most of dengue control methods involve larvicidal agents suspended or diluted in water and making active lipophilic natural products available is therefore considered a technological challenge. In this context, nanoemulsions appear as viable alternatives to solve this major problem. The present study describes the development of a novel nanoemulsion with larvicidal activity against A. aegypti along with the required Hydrophile Lipophile Balance determination of this oil. It was suggested that the mechanism of action might involve reversible inhibition of acetylcholinesterase and our results also suggest that the P. emarginatus nanoemulsion is not toxic for mammals. Thus, it contributes significantly to alternative integrative practices of dengue control, as well as to develop sucupira based nanoproducts for application in aqueous media.