This study presents the toxicological effects of iron nanoparticles (NP Fe2O3) using in vitro and in vivo tests. Initially nanoparticles were characterized physic-chemically followed by evaluation of cell viability using different cell lines. Allium cepa test and comet assay (cell lines and Danio rerio) were used for evaluation of genotoxicity. Oxidative stress analyses were performed using D. rerio exposed to NP-Fe2O3, and the enzymatic activity of the enzymes catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST) were evaluated. The results showed that initially nanoparticles had 65.55 nm, 0.24 of polydispersity of and 11.4 mV of zeta potential. Regarding cell viability, it was observed that this did not reach the IC50 up to the concentration 1 x 1010 NP mL-1. The in vitro comet assay showed that in concentrations 1.96 x108 and 109 NPs mL-1 these presented toxicity, for Allium cepa evaluation in concentrations 19.6 and 39.0 x109 NPs mL-1 presented significant damages when compared to the control. Oxidative stress showed that the liver was the most affected organ when compared to the control. Although studies show that iron nanoparticles do not lead to changes, further studies are needed to make sure they do not lead to environmental changes.
The study of characteristics of nanoscale structures and applications now has great interest of researchers from different areas. In this regard, lipid carriers can improve the bioavailability of drugs and the reduction of possible toxicological effects. Thus, the development of nanostructured systems for the agricultural sector, aimed at combating parasites may reduce extensive damage caused to livestock producers and animal health. This study aimed to prepare and characterize lipid carrier systems, such as Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC), as well as evaluate the potential of cyto and genotoxicity of these systems in order to improve and produce alternatives to the use targeting these compounds in veterinary applications. Lipid nanoparticles had become spherical with an average size of 250 nm and remained stable over 120 days. The encapsulation efficiency was greater than 99% for both drugs and release tests showed a strong interaction between drugs and nanoparticles. Cyto- and genotoxicity tests show that nanoparticles made possible changes in cellular viability of the tested cells. Thus, the results showed that the nanoparticles had good colloidal characteristics without changes in its characteristics, enabling the development of carrier systems for these drugs , aiming veterinary applications.
Agrochemicals constitute the class of products most commonly found in water resources. Their high level of concentration is due to the fact that less than 0.1% of pesticides applied to crops reach their target. The present work aims to study the sorption of clomazone herbicide (associated or not with nanoparticles). The sorption tests, performed with the 2(4) factorial design, showed that the form of herbicide is the main factor for sorption of clomazone. The application of nanoparticles as delivery system for agrochemicals is a pressing area of study and can contribute for decrease in effects of clomazone in the environment.
In this study, polymeric nanocapsules of PCL containing the herbicide atrazine were prepared. In order to optimize the preparation conditions, a 2³ factorial design was performed using different formulations of nanocapsules, which investigated the influence of three variables at two levels. The factors varied were the quantities of PCL, Span 60 and Myritol. The results were evaluated considering the size, polydispersity, zeta potential and association rate and the measures of these parameters were taken immediately after preparation and after 30 days of preparation. The formulations with minimum level of polymer in the preparation showed better stability results.
The knowledge of the structure characteristic of the Organic Matter is important for the understanding of the natural process. In this context aquatic humic substances (principal fraction) were isolated from water sample collected from the two distinct rivers, using procedure recommended for International Humic Substances Society and characterized by elemental analysis, electron paramagnetic resonance and nuclear magnetic resonance (13C NMR). The results were interpreted using principal component analysis (PCA) and the statistical analyses showed different in the structural characteristics of the aquatic humic substances studied.
Cellulose acetate polymeric membranes had been prepared by a procedure of two steps, combining the method of phase inversion and the technique of hydrolysis-deposition. The first step was the preparation of the membrane, and together was organomodified with tetraethylortosilicate and 3-aminopropyltrietoxysilane. Parameters that exert influence in the complexation of the metallic ion, as pH, time of complexation, metal concentration, had been studied in laboratory using tests of metal removal. The membranes had presented resistance mechanics and reactivity to cations, being able to be an alternative for the removal, daily pay-concentration or in the study of the lability of metals complexed.
In this paper we describe the preparation poly (L-lactide) (PLA) nanocapsules as a drug delivery system for the local anesthetic benzocaine. The characterization and in vitro release properties of the system were investigated. The characterization results showed a polydispersity index of 0.14, an average diameter of 190.1± 3 nm, zeta potential of -38.5 mV and an entrapment efficiency of 73%. The release profile of Benzocaine loaded in PLA nanocapsules showed a significant different behavior than that of the pure anesthetic in solution. This study is important to characterize a drug release system using benzocaine for application in pain treatment.
The aim of this study was to determine the pharmacokinetic parameters of liposomal ropivacaine after dental anesthesia in 14 healthy volunteers. In this randomized, double-blind and crossover study, the volunteers received maxillary infiltration of liposome-encapsulated 0.5% ropivacaine and, 0.5% ropivacaine with 1:200,000 epinephrine in two different sessions. Blood samples were collected before and after (from 15 to 1440 min) the administration of either ropivacaine formulation. HPLC with UV detection was used to quantify plasma ropivacaine concentrations. The pharmacokinetic parameters AUC0-24 (area under the plasma concentration × time curve from baseline to 24 h), AUC0-∞ (area under the plasma concentration-time curve from baseline to infinity), Cmax (maximum drug concentration), CL (renal clearance), Tmax (maximum drug concentration time), t1/2 (elimination half-life) and Vd (volume of distribution) were analyzed using the Wilcoxon signed-rank test. No differences (p > 0.05) were observed between both formulations for any of the pharmacokinetic parameters evaluated and plasma ropivacaine concentrations, considering each period of time. Both formulations showed similar pharmacokinetic profiles, indicating that the liposomal formulation could be a safer option for use of this local anesthetic, due to the absence of a vasoconstrictor.
O objetivo do presente estudo foi determinar os parâmetros farmacocinéticos da ropivacaína encapsulada em lipossomas após anestesia local em 14 voluntários sadios. Neste estudo randomizado, cruzado e duplo-cego, os voluntários receberam anestesia infiltrativa na maxila de ropivacaína a 0,5% encapsulada em lipossomas e ropivacaína 0,5% com epinefrina a 1:200.000 em duas sessões distintas. Amostras de sangue foram coletadas antes e após (de 15 a 1440 min) a administração das formulações de ropivacaína. A quantificação da concentração plasmática de ropivacaína foi feita por meio de HPLC com detecção por UV. Os parâmetros farmacocinéticos AUC0-24 (área sob a curva de concentração × tempo do tempo 0 até 24 horas) , AUC0-∞ (área sob a curva de concentração x tempo do tempo 0 até o infinito), Cmax (concentração máxima da droga), CL (clearance renal), Tmax (tempo em que ocorre a concentração máxima); t1/2 (meia vida de eliminação) e Vd (volume de distribuição) foram analisados pelo teste de Wilcoxon. Nenhuma diferença (p > 0,05) foi observada entre as duas formulações em cada parâmetro farmacocinético avaliado e as concentrações plasmáticas de ropivacaína, considerando cada período de tempo. Ambas as formulações apresentaram perfil farmacocinético semelhante, indicando que a formulação lipossomal poderia ser uma opção mais segura para o uso deste anestésico local, devido à ausência de vasoconstritor.
In this paper, we describe the preparation of alginate nanoparticles as a delivery system for the herbicide clomazone. Two different methods were investigated and characterized by size distribution, zeta potencial, pH and in vitro release. The alginate/AOT nanoparticles had higher rates of association of the herbicide clomazone than alginate/chitosan nanoparticles. Clomazone release profile, showed a significant difference in release behavior of pure herbicide in solution when compared with herbicide loaded in both alginate nanoparticles. This study is important to construct a biodegradable release system using herbicide for later release into more specific targets, avoiding contamination of environmental matrices.
Bupivacaine (S75-R25, NovaBupi®) is an amide type local anesthetic widely used. The present work consists of the development and validation of analytical methodology for evaluation of NovaBupi® content in the poly-lactide-co-glycolide nanospheres (PLGA-NS) by high performance liquid chromatography. The separation was made using the reversed-phase column LC-18, acetonitrile/phosphate buffer 85:15 v/v as mobile phase and detection at 220 nm. The results obtained show that the analytical methodology is accurate, reproducible, robust and linear over the concentration range 10-220.0 g/mL of NovaBupi®. The method was applied to determine the encapsulation efficiency and evaluate the release profile of NovaBupi®, showing good results.
Many theories about the mechanism of action of local anesthetics (LA) are described in the literature. Two types of theories can be distinguished: those that focus on the direct effects of LA on their target protein in the axon membranes, i.e. the voltage-gated sodium channel and the ones that take into account the interaction of anesthetic molecules with the lipid membrane phase for the reversible nerve blockage. Since there is a direct correlation between LA hydrophobicity and potency, it is crucial to take this physico-chemical property into account to understand the mechanism of action of LA, be it on the sodium channel protein, lipid(s), or on the whole membrane phase.
Hydroxymethylnitrofurazone (NFOH) is a prodrug that is active against Trypanosoma cruzi. It however presents low solubility and high toxicity. Hydroxypropyl-beta-cyclodextrin (HP-beta-CD) can be used as a drug-delivery system for NFOH modifying its physico-chemical properties. The aim of this work is to characterize the inclusion complex between NFOH and HP-beta-CD. The rate of NFOH release decreases after complexation and thermodynamic parameters from the solubility isotherm studies revealed that a stable complex is formed (deltaGº= 1.7 kJ/mol). This study focuses on the physico-chemical characterization of a drug-delivery formulation that comes out as a potentially new therapeutic option for Chagas disease treatment.
Characteriza of the inclusion complex ropivacaine: beta-cyclodextrin. Ropivacaine (RVC) is a widely used local anesthetic. The complexation of RVC with beta-cyclodextrin (beta-CD) is of great interest for the development of more efficient local anesthetic formulations. The present work focuses on the characterization of the RVC:beta-CD complex by nuclear magnetic resonance (NMR). The stoichiometry of the complex is 1:2 RVC:beta-CD. DOSY-NMR shows that the association constant is 55.5 M-1. Longitudinal relaxation time results show that RVC changes its mobility in the presence of beta-CD. This study is focused on the physicochemical characterization of inclusion complexes that are potentials options for pain treatment.
S(-) Bupivacaine (S(-)BVC) and Lidocaine (LDC) are widely used local anesthetics (LA). Hydroxypropyl beta-cyclodextrin (HP-beta-CD) is used as a drug-carrier system. The aim of this work was to characterize inclusion complexes between LA and HP-beta-CD. The affinity constants determined at different pHs show favourable complexation. The release kinetics experiments showed that S(-)BVC and LDC changed the released profiles in the presence of HP-beta-CD. Nuclear magnetic resonance experiments gave information about the interaction between LA and the cyclodextrin cavity. This study focused on the physicochemical characterization of drug-delivery formulations that come out as potentially new therapeutic options for pain treatment.