Rogéria de Souza Nunes

Toxicidade aguda do extrato aquoso de folhas de Erythrina velutina em animais experimentais

The aim of this work was to evaluate the acute toxicity of the aqueous extract of Erythrina velutina leaves, which is frequently used in folk medicine as a tranquilizer. The experimental design followed the Guide for Preclinical Toxicity Studies of Herbal Medicines from the Agencia Nacional de Vigilância Sanitaria (Anvisa, 2004). Adult Wistar rats were treated per os with the limit dose of 5g/kg of the extract and then observed for 14 consecutive days. No animals died and no signs of toxicity were detected either during the behavioral observations or at the autopsies, what indicates a reasonable lack of toxicity for the extract.

Compatibility study of hydroxypropylmethylcellulose films containing zidovudine and lamivudine using thermal analysis and infrared spectroscopy

Zidovudine (AZT) and lamivudine (3TC) are drugs commonly used in the treatment of acquired immune deficiency syndrome; however, these drugs have low bioavailability and short biological half-life. These factors contribute to the emergence of various side effects and lack of patient adherence to treatment. Therefore, the study of drug delivery systems is of extreme interest. In this context, this study intends to develop hydroxypropylmethylcellulose films (HPMC) containing AZT and films containing 3TC, and assess the existence of drug/polymer interactions by means of thermal analysis techniques [differential scanning calorimetry (DSC) and thermogravimetry (TG)/derivative TG (DTG)], Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD), contributing to the optimization of antiretroviral therapy. The films produced showed drying uniformity and drug distribution. DSC curves indicated that these drugs may be in an amorphous form dispersed in the polymeric matrix. Thermal decomposition profiles obtained in the TG/DTG studies of films containing drugs showed similarities with the curves of their respective physical mixtures. The FTIR spectra showed the characteristic bands conservation of AZT and 3TC isolated in the films with drugs. The results indicate that these drugs did not undergo a process of degradation or chemical interaction with the polymer that would lead to the modification or alteration of their chemical structures. XRD studies confirmed that these drugs were homogenously dispersed in the polymeric matrix. These results also showed that there was no drug/polymer incompatibility in HPMC films.

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.

An environmentally safe larvicide against Aedes aegypti based on in situ gelling nanostructured surfactant systems containing an essential oil

HYPOTHESIS Liquid crystalline precursors, which are in situ gelling nanostructured surfactant systems, can undergo phase transition in aqueous solution and become more structured aggregates, controlling release of larvicides and acting as biotechnology alternatives for dengue control. Such systems can contain bioactive substances as Citrus sinensis essential oil (CSEO) which exhibits biological activity against Aedes aegypti (Ae. aegypti) larvae. EXPERIMENTS The formulations were composed by fixed concentration of CSEO stabilized by Polyoxypropylene (5) Polyoxyethylene (20) Cetyl Ether (PPG-5 CETETH-20): oleic acid (OA) 2:1, increasing water content. The phase diagram was established and systems structure was evaluated by polarized light microscopy (PLM), small angle X-ray scattering (SAXS) and rheology. Median lethal concentration was determined against Ae. aegypti larvae. FINDINGS The phase diagram exhibited four regions: liquid crystal (LC), emulsion, microemulsion (ME) and phase separation. The PLM and SAXS distinguished microemulsions, lamellar and hexagonal LC structures. Flow and oscillatory tests showed that increasing water content increases elasticity from Newtonian to non-newtonian behavior confirming the in situ gelation behavior. The larvicidal activity of formulations indicates that these nanostructured systems improved the oil solubility in aqueous medium and in addition are potential environmental larvicide against Ae. aegypti larvae.

Larvicidal activity of Syzygium aromaticum (L.) Merr and Citrus sinensis (L.) Osbeck essential oils and their antagonistic effects with temephos in resistant populations of Aedes aegypti

Environmentally friendly botanical larvicides are commonly considered as an alternative to synthetic larvicides against Aedes aegypti Linn. In addition, mosquito resistance to currently used larvicides has motivated research to find new compounds acting via different mechanisms of action, with the goal of controlling the spread of mosquitos. Essential oils have been widely studied for this purpose. This work aims to evaluate the larvicidal potential of Syzygium aromaticum and Citrus sinensis essential oils, either alone or in combination with temephos, on Ae. aegypti populations having different levels of organophosphate resistance. The 50% lethal concentration (LC50) of the essential oils alone and in combination with temephos and the influence of essential oils on vector oviposition were evaluated. The results revealed that essential oils exhibited similar larvicidal activity in resistant populations and susceptible populations. However, S. aromaticum and C. sinensis essential oils in combination with temephos did not decrease resistance profiles. The presence of the evaluated essential oils in oviposition sites significantly decreased the number of eggs compared to sites with tap water. Therefore, the evaluated essential oils are suitable for use in mosquito resistance management, whereas their combinations with temephos are not recommended. Additionally, repellency should be considered during formulation development to avoid mosquito deterrence.

Effect of Ouratea sp. butter in the crystallinity of solid lipids used in nanostructured lipid carriers (NLCs)

The aim of this work was to evaluate the effect of Ouratea sp. butter (OB) on crystallinity of solid lipids used in nanostructured lipid carriers systems. Firstly, the composition of fatty acids in OB was evaluated by transesterification reaction for gas chromatography fatty acid methyl ester analysis. The solid lipids such as stearic acid (SA), beeswax (BW) and carnauba wax (CW) were submitted to recrystallization process (heating–cooling). Moreover, binary mixtures between solid lipids and OB were prepared in ratio 1:1 (w/w) by heating of the components above the melting point followed by cooling at room temperature. Thus, the samples were characterized by differential scanning calorimetry (DSC), thermogravimetry (TG), X ray diffraction (XRD) and hot-stage polarized optical microscopy (HSPOM). DSC curves showed a shift of the melting point to lower temperatures in the lipid mixtures with OB. TG data suggested a thermal stability reduction in the lipid mixtures containing SA and CW and an increase thermal stability in the mixture containing BW. XRD data confirmed DSC results, showing a reduction in intensity of main diffraction peaks of the lipid mixtures and a presence of the amorphous portion in angle 2θ: 22°. Finally, HSPOM demonstrated that the microstructures of solid lipids decreased in size and thickness in the mixtures containing OB at room temperature and slightly before the melting point, confirming previous characterizations. These results suggest that lipid mixtures with OB present a lower crystallinity, and it is expected that amorphous portion facilitates drug incorporation, for example.

Skin permeation, biocompatibility and antitumor effect of chloroaluminum phthalocyanine associated to oleic acid in lipid nanoparticles

The objective of this study was to develop and characterize lipid nanoparticles (LNs) containing chloroaluminum phthalocyanine (ClAlPc) to reduce the aggregation of the drug and improve its skin penetration and its antitumor effect. LNs were prepared and characterized by using stearic acid (SA) as solid lipid and oleic acid (OA) as liquid lipid in different proportions. in vitro and in vivo skin penetration was evaluated using modified Franz diffusion cells and fluorescence microscopy, respectively. in vitro biocompatibility and Photodynamic Therapy (PDT) were performed using L929-fibroblasts cell line and A549 cancer cell line and melanoma BF16-F10, respectively. OA promoted the increase in the encapsulation efficiency and drug loading, reaching values of 95.8% and 4%, respectively. The formulation with 40% OA (NLC 40) showed a significantly higher (p < 0.01) amount of drug retained in the skin compared to other formulations. All formulations developed were considered biocompatible. PDT evidenced the antitumor efficacy of NLC 40 with reduced cell viability for approximately 10% of cancer cells, demonstrating that the presence of OA in the NLC seems to potentialize this antitumor effect. PDT in BF16-F10 melanoma using NLC 40 resulted in a reduction in mean cell viability of approximately 99%. According to the results obtained, the systems developed may be promising for the incorporation of ClAlPc in the treatment of skin cancer by photodynamic therapy.

Chitosan/pvp-based mucoadhesive membranes as a promising delivery system of betamethasone-17-valerate for aphthous stomatitis

Mucoadhesive membranes were proposed in this study as drug delivery system for betamethasone-17-valerate (BMV) in the treatment of recurrent aphthous stomatitis (RAS). The membranes were obtained by using the polymers chitosan (CHI) in both presence and absence of polyvinilpyrrolidone (PVP), following the solvent evaporation method. The presence of PVP in the membranes causes significant modifications in its thermal properties. Changes in the thermal events at 114 and 193 °C (related to BMV melting point), and losses in mass (39.38 and 30.68% for CH:PVP and CH:PVP-B, respectively), suggests the incorporation of BMV in these membranes. However, the morphological aspects of the membranes do not change after adding PVP and BMV. PVP causes changes in swelling ratios (>80%) of the membranes, and it is suggested that the reorganization of the polymer mesh was highlighted by the chemical interactions between the polymers leading to different percentages of BMV released ∼40% and ∼80% from CH-B and CH:PVP-B. BMV release profile follows Korsmeyer and Peppas model (n > 0.89) which suggests that the diffusion of the drug in the swollen matrix is driven by polymer relaxation. In addition, the membranes containing PVP (higher swelling ability) present high rates of tensile strength, and therefore, higher mucoadhesion. Moreover, given the results presented, the developed mucoadhesive membranes are a promising system to deliver BMV for the treatment of RAS.

Third-Generation Transdermal Delivery Systems Containing Zidovudine: Effect of the Combination of Different Chemical Enhancers and a Microemulsion System

ABSTRACTThis study aimed to examine the influence of the combination of chemical enhancers and a microemulsion on the transdermal permeation of zidovudine (AZT). Ethanol, 1,8-cineole, and geraniol were incorporated in a microemulsion. The droplet size, zeta potential, rheology, and SAXS analysis were performed. The permeation enhancer effect was evaluated using pig ear skin. Snake skin (Boa constrictor) treated with the formulations was also used as a stratum corneum model and studied by attenuated total reflectance-infrared spectroscopy. As a result, it was observed that the incorporation of the chemical enhancers promoted a decrease of the droplet size and some rheological modifications. The 1,8-cineole associated with the microemulsion significantly increased the permeated amount of AZT. Conversely, ethanol significantly increased the quantity of the drug retained in the skin. The probable mechanism for the cineole and ethanol effects was respectively: fluidization and increasing of the diffusion coefficient, and increasing of the partition coefficient. Surprising, geraniol + microemulsion drastically decreased both the permeated and the retained amount of AZT into the skin. Thus, the adequate association of microemulsion and chemical enhancers showed to be a crucial step to enable the topical or transdermal use of drugs.