Bullfrog oil is a natural product extracted from the Rana catesbeiana Shaw adipose tissue and used in folk medicine for the treatment of several diseases. The aim of this study was to evaluate the extraction process of bullfrog oil, to develop a suitable topical nanoemulsion and to evaluate its efficacy against melanoma cells. The oil samples were obtained by hot and organic solvent extraction processes and were characterized by titration techniques and gas chromatography mass spectrometry (GC-MS). The required hydrophile-lipophile balance and the pseudo-ternary phase diagram (PTPD) were assessed to determine the emulsification ability of the bullfrog oil. The anti-tumoral activity of the samples was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for normal fibroblast (3T3) and melanoma (B16F10) cell lines. Both extraction methods produced yielded around 60% and the oil was mainly composed of unsaturated compounds (around 60%). The bullfrog oil nanoemulsion obtained from PTPD presented a droplet size of about 390 nm and polydispersity = 0.05 and a zeta potential of about´25 mV. Both the bullfrog oil itself and its topical nanoemulsion did not show cytotoxicity in 3T3 linage. However, these systems showed growth inhibition in B16F10 cells. Finally, the bullfrog oil presented itself as a candidate for the development of pharmaceutical products free from cytotoxicity and effective for antineoplastic therapy.

Asthma, a disease classified as a chronic inflammatory disorder induced by airway inflammation, is triggered by a genetic predisposition or antigen sensitization. Drugs currently used as therapies present disadvantages such as high cost and side effects, which compromise the treatment compliance. Alternatively, traditional medicine has reported the use of natural products as alternative or complementary treatment. The aim of this review was to summarize the knowledge reported in the literature about the use of natural products for asthma treatment. The search strategy included scientific studies published between January 2006 and December 2017, using the keywords “asthma,” “treatment,” and “natural products.” The inclusion criteria were as follows: (i) studies that aimed at elucidating the antiasthmatic activity of natural-based compounds or extracts using laboratory experiments (in vitro and/or in vivo); and (ii) studies that suggested the use of natural products in asthma treatment by elucidation of its chemical composition. Studies that (i) did not report experimental data and (ii) manuscripts in languages other than English were excluded. Based on the findings from the literature search, aspects related to asthma physiopathology, epidemiology, and conventional treatment were discussed. Then, several studies reporting the effectiveness of natural products in the asthma treatment were presented, highlighting plants as the main source. Moreover, natural products from animals and microorganisms were also discussed and their high potential in the antiasthmatic therapy was emphasized. This review highlighted the importance of natural products as an alternative and/or complementary treatment source for asthma treatment, since they present reduced side effects and comparable effectiveness as the drugs currently used on treatment protocols.

Chloroquine diphosphate (CQ) is a hydrophilic drug with low entrapment efficiency in hydrophobic nanoparticles (NP). Herpes simplex virus type 1 (HSV-1) is an enveloped double-stranded DNA virus worldwide known as a common human pathogen. This study aims to develop chloroquine-loaded poly(lactic acid) (PLA) nanoparticles (CQ-NP) to improve the chloroquine anti- HSV-1 efficacy. CQ-NP were successfully prepared using a modified emulsification-solvent evaporation method. Physicochemical properties of the NP were monitored using dynamic light scattering, atomic force microscopy, drug loading efficiency, and drug release studies. Spherical nanoparticles were produced with modal diameter of <300 nm, zeta potential of −20 mv and encapsulation efficiency of 64.1%. In vitro assays of CQ-NP performed in Vero E6 cells, using the MTT-assay, revealed different cytotoxicity levels. Blank nanoparticles (B-NP) were biocompatible. Finally, the antiviral activity tested by the plaque reduction assay revealed greater efficacy for CQ-NP compared to CQ at concentrations equal to or lower than 20 µg mL−1 (p < 0.001). On the other hand, the B-NP had no antiviral activity. The CQ-NP has shown feasible properties and great potential to improve the antiviral activity of drugs.

Understanding the factors that can modify the drug release profile of a drug from a Drug-Delivery-System (DDS) is a mandatory step to determine the effectiveness of new therapies. The aim of this study was to assess the Amphotericin-B (AmB) kinetic release profiles from polymeric systems with different compositions and geometries and to correlate these profiles with the thermodynamic parameters through mathematical modeling. Film casting and electrospinning techniques were used to compare behavior of films and fibers, respectively. Release profiles from the DDSs were performed, and the mathematical modeling of the data was carried out. Activation energy, enthalpy, entropy and Gibbs free energy of the drug release process were determined. AmB release profiles showed that the relationship to overcome the enthalpic barrier was PVA-fiber > PVA-film > PLA-fiber > PLA-film. Drug release kinetics from the fibers and the films were better fitted on the Peppas–Sahlin and Higuchi models, respectively. The thermodynamic parameters corroborate these findings, revealing that the AmB release from the evaluated systems was an endothermic and non-spontaneous process. Thermodynamic parameters can be used to explain the drug kinetic release profiles. Such an approach is of utmost importance for DDS containing insoluble compounds, such as AmB, which is associated with an erratic bioavailability.

Melanoma is the most aggressive and lethal type of skin cancer, with a poor prognosis because of the potential for metastatic spread. The aim was to develop innovative powder formulations for the treatment of metastatic melanoma based on micro- and nanocarriers containing 5-fluorouracil (5FU) for pulmonary administration, aiming at local and systemic action. Therefore, two innovative inhalable powder formulations were produced by spray-drying using chondroitin sulfate as a structuring polymer: (a) 5FU nanoparticles obtained by piezoelectric atomization (5FU-NS) and (b) 5FU microparticles of the mucoadhesive agent Methocel™ F4M for sustained release produced by conventional spray drying (5FU-MS). The physicochemical and aerodynamic were evaluated in vitro for both systems, proving to be attractive for pulmonary delivery. The theoretical aerodynamic diameters obtained were 0.322 ± 0.07 µm (5FU-NS) and 1.138 ± 0.54 µm (5FU-MS). The fraction of respirable particles (FR%) were 76.84 ± 0.07% (5FU-NS) and 55.01 ± 2.91% (5FU-MS). The in vitro mucoadhesive properties exhibited significant adhesion efficiency in the presence of Methocel™ F4M. 5FU-MS and 5FU-NS were tested for their cytotoxic action on melanoma cancer cells (A2058 and A375) and both showed a cytotoxic effect similar to 5FU pure at concentrations of 4.3 and 1.7-fold lower, respectively.

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Bullfrog oil (BO), a natural product obtained from recycling of adipose tissue from the amphibian Rana catesbeiana Shaw, has been recently evaluated as a therapeutic activity ingredient. This work aimed to evaluate the long-term and accelerated thermal oxidative stabilities of this product, which is a promising raw material for emulsion technology development. BO was extracted from amphibian adipose tissue at 70 °C with a yield of 60% ± 0.9%. Its main fatty acid compounds were oleic (30.0%) and eicosapentaenoic (17.6%) acids. Using titration techniques, BO showed peroxide, acid, iodine and saponification indices of 1.92 mEq·O2/kg, 2.95 mg·KOH/g oil, 104.2 g I2/100 g oil and 171.2 mg·KOH/g oil, respectively. In order to improve the accelerated oxidative stability of BO, synthetic antioxidants butylhydroxytoluene (BHT) and buthylhydroxyanisole (BHA) were used. The addition of BHT increased the oxidation induction time compared to the pure oil, or the oil containing BHA. From the results, the best oil-antioxidant mixture and concentration to increase the oxidative stability and allow the oil to be a stable raw material for formulation purposes was derived.

Abstract. Carapa guianensis, a popular medicinal plant known as "Andiroba" in Brazil, has been used in traditional medicine as an insect repellent and anti-inflammatory product. Additionally, this seed oil has been reported in the literature as a repellent against Aedes aegypti. The aim of this work is to report on the emulsification of vegetable oils such as "Andiroba" oil by using a blend of nonionic surfactants (Span 80® and Tween 20®), using the critical hydrophilic-lipophilic balance (HLB) and pseudo-ternary diagram as tools to evaluate the system's stability. The emulsions were prepared by the inverse phase method. Several formulations were made according to a HLB spreadsheet design (from 4.3 to 16.7), and the products were stored at 25°C and 4°C. The emulsion stabilities were tested both long-and short-term, and the more stable one was used for the pseudo-ternary diagram study. The emulsions were successfully obtained by a couple of surfactants, and the HLB analysis showed that the required HLB of the oil was 16.7. To conclude, the pseudo-ternary diagram identified several characteristic regions such as emulsion, micro-emulsion, and separation of phases.