Preformulation screening of lipids using solubility parameter concept in conjunction with experimental research to develop ceftriaxone loaded nanostructured lipid carriers

Abstract Development of ceftriaxone loaded nanostructured lipid carriers to increase permeability of ceftriaxone across uninflamed meninges after parenteral administration. Lipids were selected by theoretical and experimental techniques and optimization of NLCs done by response surface methodology using Box-Behnken design. The Δδt for glyceryl monostearate and Capryol90 were 4.39 and 2.92 respectively. The drug had maximum solubility of 0.175% (w/w) in glycerol monostearate and 2.56g of Capryol90 dissolved 10mg of drug. The binary mixture consisted of glyceryl monostearate and Capryol90 in a ratio of 70:30. The optimized NLCs particle size was 130.54nm, polydispersity index 0.28, % entrapment efficiency 44.32%, zeta potential -29.05mV, and % drug loading 8.10%. In vitro permeability of ceftriaxone loaded NLCs was 5.06x10-6 cm/s; evidently, the NLCs pervaded through uninflamed meninges, which, was further confirmed from in vivo biodistribution studies. The ratio of drug concentration between brain and plasma for ceftriaxone loaded NLCs was 0.29 and that for ceftriaxone solution was 0.02. With 44.32% entrapment of the drug in NLCs the biodistribution of ceftriaxone was enhanced 7.9 times compared with that of ceftriaxone solution. DSC and XRD studies revealed formation of imperfect crystalline NLCs. NLCs improved permeability of ceftriaxone through uninflamed meninges resulting in better management of CNS infections.

Encapsulation of benznidazole in nanostructured lipid carriers and increased trypanocidal activity in a resistant Trypanosoma cruzi strain

Abstract Chagas disease is a neglected parasitic disease caused by Trypanosoma cruzi, whose treatment has remained unsatisfactory for over 50 years, given that it is limited to two drugs. Benznidazole (BZN) is an efficient antichagasic drug used as the first choice, although its poor water-solubility, irregular oral absorption, low efficacy in the chronic phase, and various associated adverse effects are limiting factors for treatment. Incorporating drugs with such characteristics into nanostructured lipid carriers (NLC) is a promising alternative to overcome these limiting obstacles, enhancing drug efficacy and bioavailability while reducing toxicity. Therefore, this study proposed NLC-BZN formulations in different compositions prepared by hot-melt homogenization followed by ultrasound, and the optimized formulation was characterized by FTIR, DRX, DSC, and thermogravimetry. Biological activities included in vitro membrane toxicity (red blood cells), fibroblast cell cytotoxicity, and trypanocidal activity against epimastigotes of the Colombian strain of T. cruzi. The optimized NLC-BZN had a small size (110 nm), negative zeta potential (-18.0 mV), and high encapsulation (1.64% of drug loading), as shown by infrared spectroscopy, X-ray diffraction, and thermal analysis. The NLC-BZN also promoted lower in vitro membrane toxicity (<3% hemolysis), and 50% cytotoxic concentration (CC50) for NLC-BZN in L929 fibroblast cells (110.7 µg/mL) was twice the value as the free BZN (51.3 µg/mL). Our findings showed that the NLC-BZN had higher trypanocidal activity than free BZN against the epimastigotes of the resistant Colombian strain, and this novel NLC-BZN formulation proved to be a promising tool in treating Chagas disease and considered suitable for oral and parenteral administration

Synthesis and characterization of Sophora alopecuroides L. green synthesized of Ag nanoparticles for the antioxidant, antimicrobial and DNA damage prevention activity

Abstract In this study, it was aimed to investigate the amount of antioxidant, protective properties against DNA damage and antibacterial properties against various pathogens after the interaction of Ag metal (Ag NPs/Sa) of Sophora alopecuroides L. (S. alopecuroides L) plant seed, which is grown in Igdir and used in the treatment of many diseases. The DPPH radical quenching activity of Ag NPs/Sa was performed by using Blois method, DNA damage prevention activity by gel electrophoresis and antibacterial property by disk diffusion method. With the green synthesis method, AgNPs obtained as a result of the reaction of the plant and Ag metal are UV visible spectrophotometer (UV-vis), fourier-transformed infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and scanning electron microscope (SEM). DPPH radical quenching activity of Ag NPs/Sa was investigated in the concentration range of 25-250 µg/ml. The radical quenching activity at a concentration of 250 µg/ml was 85,215 ± 0,101%, while this value was 93,018% for the positive control BHA. It has been observed that the protective property of pBR322 plasmid DNA damage against OH radicals originating from H2O2 increases with concentration. It has been observed that Ag NPs/Sa has significant antimicrobial properties against some pathogens (B. subtilis ATCC 6633 E. coli ATCC 25952, B. cereus ATCC 10876, P. aeruginosa ATCC 27853, E. faecalis ATCC 29212, S. aureus ATTC 29213 and C. albicans ATTC 90028) that cause disease and even some pathogens are more effective than antibiotics

Development and optimization of metoclopramide containing polymeric patches: impact of permeation enhancers

Abstract The study is aimed to develop a monolithic controlled matrix transdermal patches containing Metoclopramide as a model drug by solvent casting method. Eudragit L100, Polyvinylpyrrolidone K-30, and Methylcellulose were used in different ratios and Polyethylene glycol 400 added as a plasticizer. Resulting patches were evaluated for their physicochemical characters like organoleptic characters, weight variation, folding endurance, thickness, swelling index, flatness, drug content, swelling index, percentage erosion, moisture content, water vapor transmission rate and moisture uptake. Formed patches were also evaluated through Fourier transform spectroscopy (FT-IR), X-ray diffraction (XRD), Differential Scanning calorimetry (DSC) and Scanning Electron Microscopy (SEM). Results of SEM unveiled smooth surface of drug-loaded patches. In-vitro dissolution studies were conducted by using dissolution medium phosphate buffer saline pH 7.4. Effect of natural permeation enhancers was elucidated on two optimized formulations (Z4 and Z9). Different concentrations (5%-10 %) of permeation enhancers i.e. Olive oil, Castor oil and Eucalyptus oil were evaluated on Franz diffusion cell using excised abdominal rat skin. Z4-O2 (Olive oil 10%) had enhanced sustain effect and flux value (310.72) close to the desired flux value. Z4-O2 followed Higuchi release model (R2= 0.9833) with non-fickian diffusion release mechanism (n=0.612)

Curcumin solid dispersion based on three model acrylic polymers: formulation and release properties

Abstract To investigate structure-property relationship of polymer-based curcumin solid dispersion (SD), three acrylic polymers were used to formulate curcumin SD by solvent evaporation method. Curcumin Eudragit EPO SD (cur@EPO), curcumin Eudragit RS PO SD (cur@RSPO) and curcumin Eudragit RL PO SD (cur@RLPO) showed deep red, golden orange and reddish orange color, respectively. Cur@RSPO entrapped 15.42 wt% of curcumin followed by cur@RL PO and cur@EPO. FTIR spectra indicated that in cur@EPO, curcumin may transfer hydrogen to the dimethylaminoethyl methacrylate group and thus change its color to red. In contrast, curcumin may form hydrogen bonding with Eudragit RS PO and Eudragit RL. Curcumin exists in amorphous state in three SDs as proved by differential scanning calorimetry and X-Ray diffraction measurement. In vitro digestion presented that lower pH value in simulated gastric fluid (SGF) stimulates the curcumin release from cur@EPO while permeability influences the release profile in other two SDs. When in simulated intestinal fluid (SIF), first order release model governs the release behaviors of all three SDs which showed sustained release pattern. Our results are helpful to elucidate how structure of polymer may impact on the major properties of curcumin contained SD and will be promising to broaden its therapeutic applications.

Microbialite-like structures in Cladophora sp. (Ulvophyceae) mats from a subtropical Andean basin: ecological implications / Estructuras de tipo microbialito en Cladophora sp. (Ulvophyceae) de una cuenca andina subtropical: implicaciones ecológicas

Abstract The solubility equilibrium of calcite is influenced by physicochemical, climatic and biological factors. Annual cycles of exceptionally prolonged drought, in conjunction with naturally occurring diffuse organic pollution, generate the unique conditions for the precipitation of lithified carbonate structures (microbialites). The aim of this article is to analyze the possible implications of calcite precipitation produced in mats of Cladophora sp. in an Andean subtropical basin, considering it is the first time this phenomenon is described for the region. We collected samples from selected sites at the Lules River Basin, in four sampling dates between the years 2003 and 2004, within a monitoring work of 15 years. Samples were analyzed using an electron microscope and X-ray diffraction analysis. We found that Gomphonema sp. attached to Cladophora sp. contributes to precipitation of calcite and formation of microbialite like structures, in the studied area. This work presents an initial discussion of the discovery of microbialites-like structures attached to Cladophora sp. mats in a subtropical Andean stream and the environmental conditions that lead to their production, as well as the possible ecological implications of these microbialites.(AU)

Resumen La fase sólida de las sales de los cuerpos de agua juega un papel importante en la concentración de los elementos mayoritarios. El equilibrio de solubilidad de la calcita está influenciado por factores fisicoquímicos, climáticos y biológicos. Los ciclos anuales de sequía excepcionalmente prolongada, junto con la contaminación orgánica difusa de origen natural, generan condiciones únicas para la precipitación de estructuras de carbonato litificado (microbialitos). El objetivo de este artículo es analizar las posibles implicaciones de la precipitación de calcita producida en Cladophora sp. en una cuenca subtropical andina, considerando que es la primera vez que se describe este fenómeno para la región. Recolectamos muestras en sitios seleccionados en la Cuenca del Río Lules, en cuatro fechas de muestreo entre 2003 y 2004, en el marco de un trabajo de monitoreo de quince años. Usamos red Surber para realizar los muestreos. Las muestras de algas, una vez libres de macroinvertebrados, se secaron y pesaron. Analizamos utilizando microscopía electrónica y difracción de rayos X. Encontramos que Gomphonema sp. unido a Cladophora contribuye a la precipitación de calcita y la formación de estructuras similares a microbialitos, en el área estudiada. Este trabajo presenta una discusión inicial sobre el descubrimiento de estructuras similares a microbialitos unidas a filamentos de Cladophora sp. en una cuenca andina subtropical y las condiciones ambientales que conducen a su producción, así como las posibles implicaciones ecológicas de lo mencionado anteriormente.(AU)

Biologically Synthesized Silver Nanoparticles for Enhancing Tetracycline Activity Against Staphylococcus aureus and Klebsiella pneumoniae

Abstract Phytochemical content of plant extracts can be used effectively to reduce the metal ions to nanoparticles in one-step green synthesis process. In this study, six plant extracts were used for the synthesis of silver nanoparticles (AgNPs). Biologically synthesized AgNPs was characterized using UV-Vis Spectrophotometer, Field Emission Scanning Electron Microscope (FE-SEM), X-ray diffraction (XRD), Energy Dispersive X-ray spectroscopy (EDX) and Fourier Transform Infrared (FTIR) spectroscopy. The individual and combined effects of AgNPs and tetracycline against S. aureus and K. pneumoniae were assessed. Ginger, onion and sidr extracts supported AgNPs formation while arak, garlic and mint extracts failed to convert the silver ions to AgNPs. The present findings revealed significant differences between the tested plant extracts in supporting AgNPs synthesis. AgNPs synthesized by ginger showed the highest individual and combined activity against tested strains followed by AgNPs prepared by sidr then that synthesized by onion. AgNPs significantly enhanced tetracycline activity (p≤0.05) against S. aureus and K. pneumoniae. The results of this study demonstrated that the combination of tetracycline and biologically synthesized AgNPs presented a useful therapeutically method for the treatment of bacterial infection and counterattacking bacterial resistance.

Uma exposição acidental aos raios X de um difratômetro / Accidental exposure to the X-ray of a diffractometer

As mãos de três trabalhadores foram irradiadas acidentalmente numa indústria em Camaçari, Estado da Bahia, Brasil. O diagnóstico clínico de radiodermite aguda foi possível, antes mesmo da confirmação dosimétrica da ocorrência, em virtude das manifestações cutâneas exibidas, precedidas por um eritema, e também pelas histórias ocupacionais. As avaliações das doses recebidas pelos acidentados, usando-se restituições com dosímetros termoluminescentes, tiveram boa correlação com as doses estimadas em função das manifestações clínicas. A causa imediata do acidente foi a má manutenção do equipamento que levou a sua janela posterior a ficar permanentemente aberta, porém foram fatores contributórios importantes a falta de informação dos empregados sobre os possíveis efeitos biológicos das radiações ionizantes e o não seguimento dos procedimentos operacionais corretos. A descrição deste acidente é importante, face ao grande número de difratômetros existentes em laboratórios, universidades, centros de pesquisa e indústrias. Tais aparelhos são considerados "virtualmente isentos de risco ocupacional", o que não é verdadeiro, como comprova a ocorrência que descrevemos. A evolução médica dos pacientes tem sido satisfatória, especialmente em virtude da baixa energia do feixe de raios X do difratômetro e, em conseqüência, da sua pequena penetração tissular.