In situ forming implants (ISI) prepared from biodegradable polymers such as poly(D,L-lactide) (PLA) and biocompatible solvents can be used to obtain sustained drug release after parenteral administration. The aim of this work was to study the effect of several biocompatible solvents with different physico-chemical properties on the release of ivermectin (IVM), an antiparasitic BCS II drug, from in situ forming PLA-based implants. The solvents evaluated were N-methyl-2-pyrrolidone (NMP), 2-pyrrolidone (2P), triacetine (TA) and benzyl benzoate (BB). Hansen's solubility parameters of solvents were used to explain polymer/solvent interactions leading to different rheological behaviours. The stability of the polymer and drug in the solvents were also evaluated by size exclusion and high performance liquid chromatography, respectively. The two major factors determining the rate of IVM release from ISI were miscibility of the solvent with water and the viscosity of the polymer solutions. In general, the release rate increased with increasing water miscibility of the solvent and decreasing viscosity in the following order NMP>2P>TA>BB. Scanning electron microscopy revealed a relationship between the rate of IVM release and the surface porosity of the implants, release being higher as implant porosity increased. Finally, drug and polymer stability in the solvents followed the same trends, increasing when polymer-solvent affinities and water content in solvents decreased. IVM degradation was accelerated by the acid environment generated by the degradation of the polymer but the drug did not affect PLA stability.
Ivermectin (IVM) is a BCS II drug with potent antiparasitic activity in veterinary applications. In this study, poly(lactide-co-glycolide) (PLGA) and poly(DL-lactide) (PLA) Ivermectin-loaded microparticles were prepared by the simple emulsion (O/W) solvent evaporation method in order to obtain sustained release formulations for parenteral applications. The effects of polymer end-groups (ester or free acid) and the addition of the hydrophilic polyvinylpyrrolidone polymer (PVP) in in vitro drug release profiles were also studied. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analysis showed that IVM was present in an amorphous state or as a molecular dispersion within the polymers or theirs mixtures with PVP and that a PVP-drug complex was formed. Drug entrapment efficiency in the microparticles (>90%) was independent of the polymer composition, the end groups and the presence of PVP. However, microscopic (SEM) observations showed that the addition of PVP led to more porous microparticles accompanied by the increased rates of drug release.
RESUMO Estudos demonstram que a utilização do cloro em estações de tratamento de água (ETA) pode contribuir para a formação de subprodutos orgânicos halogenados indesejados, tais como os trialometanos (TAM), quando há presença de matéria orgânica algogênica, composta de algas e cianobactérias. A Microcystis aeruginosa é uma espécie de cianobactéria com frequentes registros em eventos de florações no país e é relacionada com a formação de TAM durante a cloração da água. Desse modo, este estudo teve como objetivo o desenvolvimento e a validação do método analítico por extração líquido-líquido para detecção e quantificação de TAM por cromatografia gasosa acoplada à espectrometria de massas (ELL-CG-EM), bem como a aplicação deste para avaliar a formação de TAM em ensaios de cloração de células de Microcystis aeruginosa, simulando situações em ETA. O método obteve baixo tempo de análise (< 12 minutos), excelente seletividade, precisão, repetitividade e sensibilidade, com possibilidade de aplicação para análises de rotina em detrimento de outras técnicas consideradas mais automatizadas. Foram observadas alta demanda de cloro durante os ensaios e elevada concentração dos subprodutos quando submetida à dose de cloro gasoso (Cl2) de 2,5 e 5 mg.L-1, com destaque para o triclorometano, sendo outras espécies de monitoramento obrigatório não detectadas ou não formadas, o que pode ser justificado pela ausência de bromo.
Constructed wetlands are one of the most appropriate wastewater treatment systems in mountain areas, where altitude, slope and climate constitute major environmental and economic constraints for infrastructure construction and subsequent management. In order to protect mountain natural wetland habitats that are sensitive to ecological equilibrium disruption, instead of the more commonly used macrophytes, plant species native to upland wetlands should be preferentially implemented as a contribution to biodiversity conservation and for the creation of more efficient, more resilient and better-adapted constructed wetlands. Carex paniculata is a key macrophyte in several European mountain aquatic habitats, and one of the few high-biomass producers that can grow at sea level and at altitudes of up to 2,600 m. In this paper, the results of a 2-year investigation demonstrate the efficacy of Carex paniculata for the treatment of the mixed stormwater, sewage and livestock wastewater effluents from a typical rural settlement at 825 m above sea level in the Cantabrian Mountains. The year-round suitability of Carex paniculata for the treatment of wastewater with seasonally variable flow and composition in mountain areas is demonstrated.
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