Improvement of wound tissue repair by chitosan films containing (-)-borneol, a bicyclic monoterpene alcohol, in rats.

The aim of this study was to investigate the wound-healing activity of (-)-borneol (BOR) incorporated in chitosan film on healing protocol in rodents. To assess the BOR wound-healing potential, male Wistar rats were subjected to a full-thickness excisional wound. The animals were divided into three groups: dressed with chitosan-based film (QUIN); dressed with chitosan-based film containing 0·5% BOR (QUIBO05); or dressed with chitosan-based film containing 1% BOR (QUIBO1). Dressing the wound areas and histological analysis were performed on the 3rd, 7th, 14th, and 21st days. The myeloperoxidase (MPO) activity was assessed on the third and seventh days after surgical procedures. Wounds dressed with chitosan-based film containing BOR reduced significantly the MPO activity (P < 0·001), showed significantly larger wound retraction rates (7 days, P < 0·05), improved the granulation reaction, and also provided better collagenisation density and arrangement during wound healing. It is suggested that BOR modulates the wound-healing process and is a promising compound to be used in wound care. This product may be quite useful in improving wound healing and could be a new biotechnological product with healing properties and clinical application. Further ongoing studies will enable us to understand the precise mechanisms whereby BOR improves the wound-healing process.

Encapsulation of Citrus sinensis essential oil and R-limonene in lipid nanocarriers: A potential strategy for the treatment of leishmaniasis.

Leishmaniases, a group of neglected tropical diseases caused by an intracellular parasite of the genus Leishmania, have significant impacts on global health. Current treatment options are limited due to drug resistance, toxicity, and high cost. This study aimed to develop nanostructured lipid carriers (NLCs) for delivering Citrus sinensis essential oil (CSEO) and its main constituent, R-limonene, against leishmaniasis. The influence of surface-modified NLCs using chitosan was also examined. The NLCs were prepared using a warm microemulsion method, and surface modification with chitosan was achieved through electrostatic interaction. These nanocarriers were characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), transmission electron microscopy, and dynamic light scattering (DLS). In vitro cytotoxicity was assessed in L929 and RAW 264.7 cells, and leishmanicidal activity was evaluated against promastigote and amastigote forms. The NLCs were spherical, with particle sizes ranging from 97.9 nm to 111.3 nm. Chitosan-coated NLCs had a positive surface charge, with zeta potential values ranging from 45.8 mV to 59.0 mV. Exposure of L929 cells to NLCs resulted in over 70 % cell viability. Conversely, surface modification significantly reduced the viability of promastigotes (93 %) compared to free compounds. Moreover, chitosan-coated NLCs presented a better IC50 against the amastigote forms than uncoated NLCs. Taken together, these findings demonstrate the feasibility of using NLCs to overcome the limitations of current leishmaniasis treatments, warranting further research.

Carvacrol loaded nanostructured lipid carriers as a promising parenteral formulation for leishmaniasis treatment.

Leishmaniasis are a group of neglected infectious diseases caused by protozoa of the genus Leishmania with distinct presentations. The available leishmaniasis treatment options are either expensive and/or; cause adverse effects and some are ineffective for resistant Leishmania strains. Therefore, molecules derived from natural products as the monoterpene carvacrol, have attracted interest as promising anti-leishmania agents. However, the therapeutic use of carvacrol is limited due to its low aqueous solubility, rapid oxidation and volatilization. Thus, the development of nanostructured lipid carriers (NLCs) was proposed in the present study as a promising nanotechnology strategy to overcome these limitations and enable the use of carvacrol in leishmaniasis therapy. Carvacrol NLCs were obtained using a warm microemulsion method, and evaluated regarding the influence of lipid matrix and components concentration on the NLCs formation. NLCs were characterized by DSC and XRD as well. In addition, to the in vitro carvacrol release from NLCs, the in vitro cytotoxicity and leishmanicidal activity assays, and the in vivo pharmacokinetics evaluation of free and encapsulated carvacrol were performed. NLCs containing carvacrol were obtained successfully using a warm microemulsion dilution method. The NLCs formulation with the lowest particle size (98.42 ± 0.80 nm), narrowest size distribution (suitable for intravenous administration), and the highest encapsulation efficiency was produced by using beeswax as solid lipid (HLB=9) and 5% of lipids and surfactant. The in vitro release of carvacrol from NLCs was fitted to the Korsmeyer and Peppas, and Weibull models, demonstrating that the release mechanism is probably the Fickian diffusion type. Moreover, carvacrol encapsulation in NLCs provided a lower cytotoxicity in comparison to free carvacrol (p<0.05), increasing its in vitro leishmanicidal efficacy in the amastigote form. Finally, the in vivo pharmacokinetics of carvacrol after IV bolus administration suggests that this phenolic monoterpene undergoes enterohepatic circulation and therefore presented a long half-life (t1/2) and low clearance (Cl). In addition, C0, mean residence time (MRT) and Vdss of encapsulated carvacrol were higher than free carvacrol (p < 0.05), favoring a higher distribution of carvacrol in the target tissues. Thus, it is possible to conclude that the developed NLCs are a promising delivery system for leishmaniasis treatment.

Lippia gracilis essential oil in ß-cyclodextrin inclusion complexes: an environmentally safe formulation to control Aedes aegypti larvae.

BACKGROUND: One of the most efficient ways to prevent arboviruses, such as dengue fever, yellow fever, chikungunya and Zika, is by controlling their vector, the Aedes aegypti. Because this vector is becoming resistant to most larvicides used, the development of new larvicides should be considered. ß-Cyclodextrin (ß-CD) complexes have been investigated as an interesting way of enabling the use of essential oils in water as larvicides. This study comprised the development of Lippia gracilis essential oil (LGEO) and ß-CD inclusion complexes for control of Ae. aegypti. RESULTS: Thermal analysis clearly showed the formation of complexes using kneading and co-evaporation methods. Gas chromatography analysis showed that kneading without co-solvent (KW) gave the highest content (∼ 15%) of the LGEO major component. Moreover, KW showed that the complex had a 50% lethal concentration (LC50 ; 33 ppm) lower than that of pure LGEO (39 ppm); in other words, complexing LGEO with ß-CD improved the larvicidal activity. In addition, LGEO complexed with ß-CD (KW) was not harmful to non-target organisms at the concentrations needed to control Ae. aegypti larvae. CONCLUSION: The inclusion complex with LGEO was a feasible formulation, being economically viable, easy-to-apply and without impact on non-target organisms and, therefore, is a potential alternative larvicide for Ae. aegypti control. © 2018 Society of Chemical Industry.