Anti-inflammatory effects of α-humulene and ß-caryophyllene on pterygium fibroblasts.

AIM: To investigate the anti-inflammatory effects of the sesquiterpenes α-humulene and ß-caryophyllene on pterygium fibroblasts. METHODS: Primary cultures of pterygium fibroblasts were established. Third passage pterygium fibroblasts were exposed to α-humulene and ß-caryophyllene separately and together. The cell viability was assessed by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay at 12, 24, 48, and 72h after exposure. The levels of the inflammatory cytokines interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor (TNF)-α and IL-10 in the conditioned culture medium were assessed by enzyme-linked immunosorbent assay (ELISA) at 12, 24 and 48h after exposure. Data were statistically analyzed using Friedman repeated measures analysis of variances on ranks. RESULTS: The 25 µmol/L ß-caryophyllene induced significant decrease in the IL-6 production by pterygium fibroblasts 48h after the exposure (P=0.041). The levels of IL-1ß, IL-8, IL-10, and TNF-α were very low and had no statistically significant variations after exposure to α-humulene, ß-caryophyllene, or both compounds together. CONCLUSION: The exposure to 25 µmol/L of ß-caryophyllene significantly reduce the production of IL-6 by pterygium fibroblasts after 48h. This sesquiterpene may be a potential alternative adjuvant agent for the treatment of pterygium.

Inhalation of dimethyl fumarate-encapsulated solid lipid nanoparticles attenuate clinical signs of experimental autoimmune encephalomyelitis and pulmonary inflammatory dysfunction in mice.

RATIONALE: The FDA-approved Dimethyl Fumarate (DMF) as an oral drug for Multiple Sclerosis (MS) treatment based on its immunomodulatory activities. However, it also caused severe adverse effects mainly related to the gastrointestinal system. OBJECTIVE: Investigated the potential effects of solid lipid nanoparticles (SLNs) containing DMF, administered by inhalation on the clinical signs, central nervous system (CNS) inflammatory response, and lung function changes in mice with experimental autoimmune encephalomyelitis (EAE). MATERIALS AND METHODS: EAE was induced using MOG35-55 peptide in female C57BL/6J mice and the mice were treated via inhalation with DMF-encapsulated SLN (CTRL/SLN/DMF and EAE/SLN/DMF), empty SLN (CTRL/SLN and EAE/SLN), or saline solution (CTRL/saline and EAE/saline), every 72 h during 21 days. RESULTS: After 21 days post-induction, EAE mice treated with DMF-loaded SLN, when compared with EAE/saline and EAE/SLN, showed decreased clinical score and weight loss, reduction in brain and spinal cord injury and inflammation, also related to the increased influx of Foxp3+ cells into the spinal cord and lung tissues. Moreover, our data revealed that EAE mice showed signs of respiratory disease, marked by increased vascular permeability, leukocyte influx, production of TNF-α and IL-17, perivascular and peribronchial inflammation, with pulmonary mechanical dysfunction associated with loss of respiratory volumes and elasticity, which DMF-encapsulated reverted in SLN nebulization. CONCLUSION: Our study suggests that inhalation of DMF-encapsulated SLN is an effective therapeutic protocol that reduces not only the CNS inflammatory process and disability progression, characteristic of EAE disease, but also protects mice from lung inflammation and pulmonary dysfunction.

Cellulose Nanofibers Improve the Performance of Retrograded Starch/Pectin Microparticles for Colon-Specific Delivery of 5-ASA.

Cellulose nanofibers (CNF) were employed as the nanoreinforcement of a retrograded starch/pectin (RS/P) excipient to optimize its colon-specific properties. Although starch retrogradation ranged from 32 to 73%, CNF addition discretely disfavored the RS yield. This result agrees with the finding that in situ CNF reduces the presence of the RS crystallinity pattern. A thermal analysis revealed that the contribution of pectin improves the thermal stability of the RS/CNF mixture. Through a complete factorial design, it was possible to optimize the spray-drying conditions to obtain powders with high yield (57%) and low moisture content (1.2%). The powders observed by Field Emission Gum Scanning Electron Microscopy (FEG-SEM) had 1-10 µm and a circular shape. The developed methodology allowed us to obtain 5-aminosalicilic acid-loaded microparticles with high encapsulation efficiency (16-98%) and drug loading (1.97-26.63%). The presence of CNF in RS/P samples was responsible for decreasing the burst effect of release in simulated gastric and duodenal media, allowing the greatest mass of drug to be targeted to the colon. Considering that spray-drying is a scalable process, widely used by the pharmaceutical industry, the results obtained indicate the potential of these microparticles as raw material for obtaining other dosage forms to deliver 5-ASA to the distal parts of gastrointestinal tract, affected by inflammatory bowel disease.

A Functional Wound Dressing as a Potential Treatment for Cutaneous Leishmaniasis.

Cutaneous leishmaniasis (CL) is a parasitic disease characterized by progressive skin sores. Currently, treatments for CL are limited to parenteral administration of the drug, which presents severe adverse effects and low cure rates. Therefore, this study aimed to develop poly(vinyl-alcohol) (PVA) hydrogels containing Amphotericin B (AmB) intended for topical treatment of CL. Hydrogels were evaluated in vitro for their potential to eliminate promastigote forms of Leishmania spp., to prevent secondary infections, to maintain appropriate healing conditions, and to offer suitable biocompatibility. AmB was incorporated into the system in its non-crystalline state, allowing it to swell more and faster than the system without the drug. Furthermore, the AmB release profile showed a continuous and controlled behavior following Higuchi´s kinetic model. AmB-loaded-PVA-hydrogels (PVA-AmB) also showed efficient antifungal and leishmanicidal activity, no cytotoxic potential for VERO cells, microbial impermeability and water vapor permeability compatible with the healthy skin's physiological needs. Indeed, these results revealed the potential of PVA-AmB to prevent secondary infections and to maintain a favorable environment for the healing process. Hence, these results suggest that PVA-AmB could be a suitable and efficient new therapeutic approach for the topical treatment of CL.

An analytical GC-MS method to quantify methyl dihydrojasmonate in biocompatible oil-in-water microemulsions: physicochemical characterization and in vitro release studies.

Microemulsions (MEs) loaded with methyl dihydrojasmonate (MJ) were developed to improve the aqueous solubility of this drug. The composition of the formulations ranged according to the oil/surfactant ratio (O/S). The MEs were characterized according to diameter of droplets, X-ray diffraction and polarized light microscopy. The MJ identification and quantification was performed by gas chromatography-mass spectrometry (GC-MS). The MJ showed a retention time of ∼16.7 min for all samples. The obtained correlation coefficient from the calibration graph was 0.991. The developed analytical method was effective enough to quantify low and high concentrations of MJ. The increase of the O/S ME ratio led to a reduction of the droplet diameter. All formulations showed an amorphous structure and the behavior varied between isotropic and anisotropic systems. A decrease in the release of MJ with the increase of the O/S ratio in the formulations was observed. The analytical method developed for the quantitative determination of MJ is suitable to detect and quantify the drug compound from different compositions of MEs in the in vitro release test, and by analogy in other prolonged effects related to the drug reservoir effect of these systems was observed, revealing that ME can be a promising nanocarrier for MJ delivery to tumor cells.

Understanding Drug Release Data through Thermodynamic Analysis.

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.

Development and Characterization of a Microemulsion System Containing Amphotericin B with Potential Ocular Applications.

BACKGROUND: Amphotericin B eye drops are widely used in the treatment of ocular infections. However, amphotericin's toxicity leads to low patient compliance and aggravation of symptoms. This work describes the development of a microemulsion system containing amphotericin B, aiming for its use in ocular applications. METHODS: The microemulsion was developed by the titration technique. The physicochemical characteristics were determined with both loaded and unloaded amphotericin B-microemulsion. The nanostructures were analyzed by polarized light microscopy. The microdilution method was used to establish the minimum inhibitory concentration against fungal strains, and, therefore, evaluate the microemulsion activity. Additionally, in order to evaluate the microemulsion toxicity an in vitro toxicity assay against red blood cells was performed. RESULTS: The performed studies showed that the presence of amphotericin B loaded into the system did not induce serious changes in the physicochemical properties of the microemulsion when compared to the unloaded system. The spectrophotometric studies depicted amphotericin B-self-associated species, which allow predicting its behavior in vitro. The high pressure liquid chromatography results revealed high drug content entrapment in the microemulsion droplet. Finally, the amphotericin B-microemulsion in vitro susceptibility test showed high activity against Candida strains and a low toxicity profile against red blood cells when compared to Fungizone®. CONCLUSION: The physicochemical characterization of the microemulsion demonstrated that its characteristics are compatible with the topical ocular route, making it eligible for consideration as a new and interesting amphotericin B-deliverydosage form to be used as eye drop formulation.

Development and Characterization of a Biocompatible Soybean Oil-Based Microemulsion for the Delivery of Poorly Water-Soluble Drugs.

The aim of this work was the development and characterization of a biocompatible microemulsion (ME) containing soybean oil (O), phosphatidylcholine/sodium oleate/Eumulgin®HRE40 as the surfactant mixture (S) and water or buffer solution as the aqueous phase (W), for oral delivery of the poorly water-soluble drugs sulfamerazine (SMR) and indomethacin (INM). A wide range of combinations to obtain clear oil-in-water (o/w) ME was observed from pseudo-ternary phase diagrams, which was greater after the incorporation of both drugs, suggesting that they acted as stabilizers. Drug partition studies indicated a lower affinity of the drugs for the oil domain when they were ionized and with increased temperature, explained by the fact that both drugs were introduced inside the oil domain, determined by nuclear magnetic resonance. High concentrations of SMR and INM were able to be incorporated (22.0 and 62.3 mg/mL, respectively). The ME obtained presented an average droplet size of 100 nm and a negative surface charge. A significant increase in the release of SMR was observed with the ME with the highest percentage of O, because of the solubilizing properties of the ME. Also, a small retention effect was observed for INM, which may be explained by the differences in the partitioning properties of the drugs.

Multifunction hexagonal liquid-crystal containing modified surface TiO2 nanoparticles and terpinen-4-ol for controlled release.

Multifunctional products have been developed to combine the benefits of functional components and terpinen-4-ol (TP) delivery systems. In this way, p-toluene sulfonic acid modified titanium dioxide (TiO2) nanoparticles and TP, an antioxidant, have been incorporated in liquid-crystalline formulations for photoprotection and controlled release of the TP, respectively. By X-ray powder diffraction and diffuse reflectance spectroscopy, we noted that using p-toluene sulfonic acid as a surface modifier made it possible to obtain smaller and more transparent TiO2 nanoparticles than those commercially available. The liquid-crystalline formulation containing the inorganic ultraviolet filter was classified as broad-spectrum performance by the absorbance spectroscopy measurements. The formulations containing modified TiO2 nanoparticles and TP were determined to be in the hexagonal phase by polarized light microscopy and small-angle X-ray scattering, which makes possible the controlled released of TP following zero-order kinetics. The developed formulations can control the release of TP. Constant concentrations of the substance have been released per time unit, and the modified TiO2 nanoparticles can act as a transparent inorganic sunscreen.

Oil-in-water biocompatible microemulsion as a carrier for the antitumor drug compound methyl dihydrojasmonate.

Methyl dihydrojasmonate (MJ) has been studied because of its application as an antitumor drug compound. However, as MJ is a poorly water-soluble compound, a suitable oil-in-water microemulsion (ME) has been studied in order to provide its solubilization in an aqueous media and to allow its administration by the parenteral route. The ME used in this work was characterized on the pseudo-ternary phase diagram by dynamic light scattering and rheological measurements. Regardless of the drug presence, the droplet size was directly dependent on the oil/surfactant (O/S) ratio. Furthermore, the drug incorporation into the ME significantly increased the ME diameter, mainly at low O/S ratios. The rheological evaluation of the systems showed that in the absence of drug a Newtonian behavior was observed. On the other hand, in the presence of MJ the ME systems revealed pseudoplastic behavior, independently of the O/S ratio. The in vivo studies demonstrated that not only was the effect on the tumor inhibition inversely dependent on the MJ-loaded ME administered dose, but also it was slightly higher than the doxorubicin alone, which was used as the positive control. Additionally, a small antiangiogenic effect for MJ-loaded ME was found at doses in which it possesses antitumor activity. MJ revealed to be nontoxic at doses higher than 350 mg/kg, which was higher than the dose that provides tumor-inhibition effect in this study. Because the MJ-loaded ME was shown to have anticancer activity comparable to doxorubicin, the ME described here may be considered a suitable vehicle for parenteral administration of MJ.

Solubility and release modulation effect of sulfamerazine ternary complexes with cyclodextrins and meglumine.

This study investigated the effect on solubility and release of ternary complexes of sulfamerazine (SMR) with ß-(ßCD), methyl-(MßCD) and hydroxypropyl-ß-cyclodextrin (HPßCD) using meglumine (MEG) as the ternary component. The combination of MEG with MßCD resulted the best approach, with an increased effect (29-fold) of the aqueous solubility of SMR. The mode of inclusion was supported by 2D NMR, which indicated that real ternary complexes were formed between SMR, MEG and MßCD or HPßCD. Solid state analysis was performed using Fourier-transform infrared spectroscopy (FT IR), differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD), which demonstrated that different interactions occurred among SMR, MEG and MßCD or HPßCD in the ternary lyophilized systems. The ternary complexes with ßCD and MßCD produced an additional retention effect on the release of SMR compared to the corresponding binary complexes, implying that they were clearly superior in terms of solubility and release modulation.

Development and characterization of biocompatible isotropic and anisotropic oil-in-water colloidal dispersions as a new delivery system for methyl dihydrojasmonate antitumor drug.

Microemulsions (MEs) are colloidal systems that can be used for drug-delivery and drug-targeting purposes. These systems are able to incorporate drugs modifying bioavailability and stability and reducing toxic effects. The jasmonate compounds belong to a group of plant stress hormones, and the jasmonic acid and its methyl ester derivative have been described as having anticancer activity. However, these compounds are very poorly water-soluble, not allowing administration by an intravenous route without an efficient nanostructured carrier system. In this work, biocompatible MEs of appropriate diameter size for intravenous route administration, loaded and unloaded with methyl dihydrojasmonate (MJ), were developed and described in a pseudo-ternary phase diagram. The compositions of the MEs were carefully selected from their own regions in the pseudo-ternary phase diagram. The formulations were analyzed by light scattering, polarized light microscopy, and X-ray diffraction. Also, a study on rheological profile was performed. The results showed that the droplet size decreased with both MJ incorporation and oil phase/surfactant ratio. All compositions of the studied MEs showed rheological behavior of pseudoplastic fluid and amorphous structures. In the absence of MJ, most of the studied MEs had thixotropic characteristics, which became antithixotropic in the presence of the drug. Almost all MJ-unloaded MEs presented anisotropic characteristics, but some formulations became isotropic, especially in the presence of MJ. The results of this study support the conclusion that the studied system represents a promising vehicle for in vivo administration of the MJ antitumor drug.

Producing xylan/Eudragit® S100-based microparticles by chemical and physico-mechanical approaches as carriers for 5-aminosalicylic acid.

Xylan is a biopolymer found in a variety of cell wall plants. Eudragit® S-100 (ES100), a pH-dependent polymer, is used as a coating material in gastroresistant delivery systems. In this study, microparticles based on both polymers were produced by interfacial cross-linking polymerisation and/or spray-drying technique in order to investigate feasibility and stability of the systems. Size and morphology of the microparticles were characterised by optical and SEM while FT-IR, thermal analysis (TG/DTA), and X-ray diffraction (XRD) evaluated the drug-polymer interactions and the thermal behaviour of the systems. FT-IR confirmed the absence of chemical interaction between the polymers. TG/DTA analysis showed a higher stability for spray-dried microparticles and XRD data proved the amorphous feature of both carriers. The results reveal that xylan/ES100 microparticles can be produced by chemical or physico-mechanical ways, the latter being the best option due to the lack of toxic cross-linking agents and easy scale-up.

Aspectos fundamentais no desenvolvimento de sistemas microemulsionados contendo anfotericina B para uso oftálmico / An overview of the development of microemulsion systems containing amphotericin B for ophthalmic use

A exemplo do que ocorre com outros fármacos, a biodisponibilidade da anfotericina B (AmB) através da via ocular repreesenta um grande desafio para a pesquisa científica. Na verdade, a baixa biodisponibilidade apresentada por tal molécula é devido, principalmente, a presença das barreiras oculares que impedem a absorção deste fármaco para os tecidos internos. A toxicidade associada a este fármaco, assim como a sua baixa capacidade em permear a córnea íntegra também consiste em um problema associado ao seu uso clínico. Novos veículos seguros e eficazes para a liberação ocular da AmB são, portanto, necessários. As microemulsões (MEs) aparecem como um interessante sistema devido à sua transparência, estabilidade termodinâmica e favorável viscosidade. O conhecimento do processo de formação das MEs contendo AmB, assim como a compreensão de toda a sua caracterização físico-química correspondem a aspectos importantes para se determinar as condições favoráveis para que estes sistemas venham a ser empregados como colírios. Esta revisão tem como objetivo, portanto, abordar este tema enfatizando os principais aspectos relacionados com a utilização de MEs como sistemas de liberação para a AmB através da via tópica oftálmica.

As occurs with a number of drugs, the bioavailability of amphotericin B (AmB) used to treat fungal infections by the ocular route remains a great challenge to research scientists. In fact, the poor bioavailability of AmB is due mainly to the corneal barrier, which leads to a precorneal loss and consequent decrease in the absorption of this drug into the intraocular tissues. The toxicity associated with this molecule, together with its poor ability to penetrate the intact corneal epithelium, also represents a major drawback to its clinical use. New effective and safe drug vehicles for ocular delivery of AmB are therefore urgently needed. Microemulsions (MEs) seem to be an interesting system, owing to their transparent appearance, thermodynamic stability and favorable viscosity. Knowledge of the process of formation of AmB-containing MEs, as well as a good understanding of the physical chemistry of such systems, would provide reliable information on the best conditions for the use of these systems as eye drops. The goal of this research was thus to make an approach to this subject by reviewing the main studies on the use of MEs as delivery systems for AmB in topical eye treatment.

Diagnosis of public programs focused on herbal medicines in Brazil / Diagnóstico de los programas de fitoterapia, inscrita en el sistema de salud pública en Brasil

The present study is aimed to diagnose the current public programs focused on herbal medicine in Brazil where the following results can be observed. The main purpose of implementation of these programs was the demand of the users of medicinal plants and herbal medicines. The initiative of the implementation of these programs was related to the managers (58 percent). The difficulties in this implementation were due to lack of funding (90 percent) of the programs. In 80 percent of the programs, the physicians did not adhere to herbal medicine services due to lack of knowledge in the subject. Training courses were proposed (70 percent) to increase the adhesion of prescribers to the system. Some municipalities use information obtained from patients to assess the therapeutic efficiency of medicinal plants and herbal medicines. Of the programs underway, cultivation of medicinal plants was observed in 50 percent, and 67 percent of the programs adopted quality control. In most programs, this control is not performed in accordance with the legal requirements.

Este trabajo tiene como objetivo diagnosticar los programas de fitoterapia en actividad en Brasil, donde se pudo verificar los siguientes resultados. El motivo principal para la implantación de los programas fue la demanda de los usuarios de plantas medicinales y fitoterápicos. La iniciativa de la implantación de los programas está relacionada a los gestores (58 por ciento). Las dificultades en la implantación o están relacionadas a la falta de recursos financieros (90 por ciento) de los programas. En 80 por ciento de los programas, los médicos no adhirieron a los servicios de fitoterapia por falta de conocimiento del asunto. Cursos de capacitación fueron propuestos (70 por ciento) para aumentar la concordancia de los prescriptores al sistema. Parte de los municipios utiliza informaciones de los pacientes para la evaluación de la eficiencia terapéutica de las plantas medicinales y fitoterápicos. De los programas en actividad, 50 por ciento cultivan plantas medicinales y 67 por ciento realizan control de calidad. En la mayoría de los programas ese control no atiende a la legislación vigente.

Trends in rheumatic fever: clinical aspects and perspectives in prophylactic treatments.

INTRODUCTION: Rheumatic fever (RF), a systemic illness that may occur following Group A beta-hemolytic streptococcal (GABHS) pharyngitis in children, is a major problem in countries with limited resources. Because of its long track record and low cost, an injection of benzathine penicillin G (BPG) suspension every 3 or 4 weeks has been used as secondary prophylaxis. Despite its excellent in vitro efficacy, the inability of BPG to eradicate GABHS has been frequently reported. AREAS COVERED: This work reviews the possible causes of failure, as well as the inconvenience of the current prophylactic treatment of acute RF and suggests a new pharmacotherapeutic system that could replace the current one. EXPERT OPINION: RF is a major problem concerning only countries with limited resources and could be considered as a neglected disease. The dose regimen using BPG suspension results in failures, which could be avoided by the use of nanocarrier-based systems. To meet this ultimate goal, the research should be transposed from the laboratory scale to an industrial and clinical application level. This research should be conducted to produce a pharmaceutical dosage form that will be commercially available, consumed by and affordable for patients. However, health, environmental and socioeconomic hazards should be considered.

Structural properties induced by the composition of biocompatible phospholipid-based microemulsion and amphotericin B association.

Anionic microemulsions (MEs) containing soya phosphatidylcholine, Tween-20, sodium oleate as surfactant, and cholesterol as oil phase were investigated as drug carriers for amphotericin B. Depending on the composition of the microemulsion, various structures, which differently interact with amphotericin B, can be formed. The nanostructured systems were characterized by photon correlation spectroscopy, rheological behavior, and polarized light microscopy. The results reveal that the droplet diameters increased with amphotericin B incorporation for all ranges of surfactant and oil phase. For both amphotericin B-unloaded and amphotericin B-loaded microemulsions, the profile of the oil droplet diameter decreased with increasing the surfactant concentration, demonstrating the stabilizing effect of the surfactant. The increase in the oil phase proportions led to the growth of the droplet diameter, clearly demonstrating the limit of the surfactant organization in the oil-water interface. The amphotericim B incorporation into microemulsion increased with the fraction volume of the oil phase and the surfactant concentration reaching a plateau at high contents. This profile could be quantitatively analyzed by the framework of the pseudo-phase model that considers the amphotericim B distribution between the oil and the aqueous phases. The rheological analysis showed a pseudoplastic behavior with little thixotropic characteristic. Under polarized light, the system of interest showed a dark background characteristic of dispersed droplets. However, for both amphotericim B-loaded and amphotericim B unloaded microemulsions, the increase in the O/S ratio led to the formation of ordered structures with lamellar arrangements.

How can micelle systems be rebuilt by a heating process?

The aim of this work was to evaluate how an aqueous micellar system containing Amphotericin B (AmB) and sodium deoxycholate (DOC) can be rebuilt after heating treatment. Also, a review of the literature on the physicochemical and biological properties of this new system was conducted. Heated (AmB-DOC-H) and unheated (AmB-DOC) micelles were then diluted at four different concentrations (50 mg · L(-1), 5 mg · L(-1), 0.5 mg · L(-1), and 0.05 mg · L(-1)) to perform physicochemical studies and a pharmacotoxicity assay, in which two cell models were used for the in vitro experiments: red blood cells (RBC) from human donors and Candida parapsilosis (Cp). While potassium (K(+)) and hemoglobin leakage from RBC were the parameters used to evaluate acute and chronic toxicity, respectively, the efficacy of AmB-DOC and AmB-DOC-H were assessed by K(+) leakage and cell survival rate from Cp. The spectral study revealed a slight change in the AmB-DOC aggregate peak from 327 nm to 323 nm, which is the peak for AmB-DOC-H. Although AmB-DOC and AmB-DOC-H exhibited different behavior for hemoglobin leakage, AmB-DOC produced higher leakage than AmB-DOC-H at high concentrations (from 5 mg · L(-1)). For K(+) leakage, both AmB-DOC and AmB-DOC-H showed a similar profile for both cell models, RBC and Cp (P < 0.05). AmB-DOC-H and AmB-DOC also revealed a similar profile of activity against Cp with an equivalent survival rate. In short, AmB-DOC-H showed much less toxicity than AmB-DOC, but remained as active as AmB-DOC against fungal cells. The results highlight the importance of this new procedure as a simple, inexpensive, and safe way to produce a new kind of micelle system for the treatment of systemic fungal infections.

Physical factors affecting plasmid DNA compaction in stearylamine-containing nanoemulsions intended for gene delivery.

Cationic lipids have been used in the development of non-viral gene delivery systems as lipoplexes. Stearylamine, a cationic lipid that presents a primary amine group when in solution, is able to compact genetic material by electrostatic interactions. In dispersed systems such as nanoemulsions this lipid anchors on the oil/water interface confering a positive charge to them. The aim of this work was to evaluate factors that influence DNA compaction in cationic nanoemulsions containing stearylamine. The influence of the stearylamine incorporation phase (water or oil), time of complexation, and different incubation temperatures were studied. The complexation rate was assessed by electrophoresis migration on agarose gel 0.7%, and nanoemulsion and lipoplex characterization was done by Dynamic Light Scattering (DLS). The results demonstrate that the best DNA compaction process occurs after 120 min of complexation, at low temperature (4 ± 1 °C), and after incorporation of the cationic lipid into the aqueous phase. Although the zeta potential of lipoplexes was lower than the results found for basic nanoemulsions, the granulometry did not change. Moreover, it was demonstrated that lipoplexes are suitable vehicles for gene delivery.

Diagnosis of public programs focused on herbal medicines in Brazil.

The present study is aimed to diagnose the current public programs focused on herbal medicines in Brazil by means of in loco visits to 10 programs selected by means of questionnaires sent to 124 municipalities that count on herbal medicine services. The main purpose of the implementation of program programs is related to the development of medicinal herbs. 70% of them are intended for the production of herbal medicines and 50% are aimed to ensure the access of the population to medicinal plants and or herbal medicines. The initiative of the implementation of these programs was related to the managers (60%). The difficulties in this implementation were due to the lack of funding (100%) of the programs. In 60% of the programs, the physicians did not adhere to herbal medicine services due to the lack of knowledge of the subject. Training courses were proposed (80%) to increase the adhesion of prescribers to the system. Some municipalities use information obtained from patients to assess the therapeutic efficiency of medicinal plants and herbal medicines. Of the programs underway, cultivation of medicinal plants was observed in 90% and 78% of them adopt quality control. In most programs, this control is not performed in accordance with the legal requirements. The programs focused on medicinal plants and herbal medicines implemented in Brazil face some chronic problems of infrastructure, management, operational capacity and self-sustainability, which can be directly related to the absence of a national policy on medicinal plants and herbal medicines.