Obtenção e caracterização de sistemas particulados de quitosana para liberação gástrica de amoxicilina

The infection caused by Helicobacter pylori (H. pylori) is associated with gastroduodenal inflammation can lead to the development of gastritis, gastric or duodenal ulcer and gastric cancer (type 1 carcinogen for stomach cancer). Amoxicillin is used as first-line therapy in the treatment of H. pylori associated to metronidazole or clarithromycin, and a proton pump inhibitor. However, the scheme is not fully effective due to inadequate accumulation of antibiotics in gastric tissue, inadequate efficacy of ecological niche of H. pylori, and other factors. In this context, this study aimed to obtaining and characterization of particulate systems gastrorretentivos chitosan - amoxicillin aiming its use for treatment of H. pylori infections. The particles were obtained by the coacervation method / precipitation using sodium sulfate as precipitating agent and crosslinking and two techniques: addition of amoxicillin during preparation in a single step and the sorption particles prior to amoxycillin prepared by coacervation / precipitation and spray drying. The physicochemical characterization of the particles was performed by SEM, FTIR, DSC, TG and XRD. The in vitro release profile of amoxycillin free and incorporated in the particles was obtained in 0.1 N HCl (pH = 1.2). The particles have higher encapsulation efficiency to 80% spherical shape with interconnected particles or adhered to each other, the nanometric diameter to the systems obtained by coacervation / precipitation and fine for the particles obtained by spray drying. The characterization by FTIR, DSC and XRD showed that the drug was incorporated into the nanoparticles dispersed in the polymeric matrix. Thermal analysis (TG and DSC) indicated that encapsulation provides greater heat stability to the drug. Amoxicillin encapsulated in nanoparticles had slower release compared to free drug. The particles showed release profile with a faster initial stage (burst effect) reaching a maximum at 30 minutes 35% of amoxicillin for the system in 1: 1 ratio relative to the polymer and 80% for the system in the ratio 2: 1. Although simple and provide high encapsulation efficiency of amoxicillin, the process of coacervation, precipitation in one step using sodium sulfate as precipitant / cross-linker must be optimized in order to adjust the release kinetics according to the intended application.

Nanopartículas catiônicas de poli (ácido lático) para liberação modificada de peptídios da peçonha do escorpião Tityus serrulatus

Reported accidents involving the poisoning scorpions are still frequent in Brazil, mainly caused by Tityus serrulatus, known as yellow scorpion. Although antivenom sera are produced routinely by various government laboratories, the effectiveness of its use depends on how quickly treatment is initiated and efficiency in the production of antibodies by the immunized animals. In this study, the development of cationic polymeric nanoparticles of poly(lactic acid) aimed to create a modified delivery system for peptides and proteins of T. serrulatus venom, able to enhance the production of serum antibodies against the scorpion toxins. The cationic nanoparticles were obtained by a low energy nanoprecipitation, after study of the parameters’ variations effects over the physicochemical properties of the particles. The surface functionalization of the nanoparticles with the hyperbranched polyethyleneimine was proved by zeta potential analysis and enabled the adsorption by electrostatic interaction of different types of proteins. The protein loading efficiency of 40-80 % to bovine serum albumin (BSA) and 100 % to scorpion venom peptides evaluated by spectrophotometry and polyacrylamide gel electrophoresis confirmed the success of the selected parameters established for obtainment of nanoparticles, produced with size between 100 to 250 nm. The atomic force microscopy analysis and in vitro release showed that the spherical nanoparticles provided a sustained release profile of proteins by diffusion mechanism, demonstrating the potential for application of the nanoparticles in vivo.

Nanopartículas catiônicas de poli (ácido lático) para liberação modificada de peptídios da peçonha do escorpião Tityus serrulatus

Reported accidents involving the poisoning scorpions are still frequent in Brazil, mainly caused by Tityus serrulatus, known as yellow scorpion. Although antivenom sera are produced routinely by various government laboratories, the effectiveness of its use depends on how quickly treatment is initiated and efficiency in the production of antibodies by the immunized animals. In this study, the development of cationic polymeric nanoparticles of poly(lactic acid) aimed to create a modified delivery system for peptides and proteins of T. serrulatus venom, able to enhance the production of serum antibodies against the scorpion toxins. The cationic nanoparticles were obtained by a low energy nanoprecipitation, after study of the parameters’ variations effects over the physicochemical properties of the particles. The surface functionalization of the nanoparticles with the hyperbranched polyethyleneimine was proved by zeta potential analysis and enabled the adsorption by electrostatic interaction of different types of proteins. The protein loading efficiency of 40-80 % to bovine serum albumin (BSA) and 100 % to scorpion venom peptides evaluated by spectrophotometry and polyacrylamide gel electrophoresis confirmed the success of the selected parameters established for obtainment of nanoparticles, produced with size between 100 to 250 nm. The atomic force microscopy analysis and in vitro release showed that the spherical nanoparticles provided a sustained release profile of proteins by diffusion mechanism, demonstrating the potential for application of the nanoparticles in vivo.

Nanopartículas de alginato como sistema de liberação para o herbicida clomazone

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.

Desenvolvimento e caracterização de nanocápsulas de poli (L-lactídeo) contendo benzocaína

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.

Poly(Lactide-co-Glycolide) Nanocapsules Containing Benzocaine: Influence of the Composition of the Oily Nucleus on Physico-Chemical Properties and Anesthetic Activity

The aim of this work was to investigate the influence of the oily nucleus composition on physico-chemical properties and anesthetic activity of poly (lactide-co-glycolide) nanocapsules with benzocaine.Nanocapsules containing benzocaine were prepared with three different oily nucleus composition and characterized by mean diameter, polydispersivity, zeta potential, pH and stability were investigated as a function of time. In vitro release kinetics were performed in a system with two compartments separated by a cellulose membrane. Intensity and duration of analgesia were evaluated in rats by sciatic nerve blockade.The greatest stability, slower release profile and improvement in the local anesthetic activity of BZC were obtained with the formulation using USP mineral oil as component.Results from our study provide useful perspectives on selection of the primary materials needed to produce suspensions of polymeric nanocapsules able to act as carriers of BZC, with potential future application in the treatment of pain.

Polymeric alginate nanoparticles containing the local anesthetic bupivacaine

Bupivacaine (BVC; S75-R25, NovaBupirelease kinetics showed a different behavior for the release profile of BVC in solution, compared with BVC-loaded alginate nanoparticles. In vitro and in vivo assays showed that alginate-chitosan BVC (BVC(ALG-CHIT)) and alginate-AOT BVC (BVC(ALG-AOT)) presented low cytotoxicity in 3T3-fibroblasts, enhanced the intensity, and prolonged the duration of motor and sensory blockades in a sciatic nerve blockade model.

Paraquat-loaded alginate/chitosan nanoparticles: Preparation, characterization and soil sorption studies

Agrochemicals are amongst the contaminants most widely encountered in surface and subterranean hydrological systems. They comprise a variety of molecules, with properties that confer differing degrees of persistence and mobility in the environment, as well as different toxic, carcinogenic, mutagenic and teratogenic potentials, which can affect non-target organisms including man. In this work, alginate/chitosan nanoparticles were prepared as a carrier system for the herbicide paraquat. The preparation and physicochemical characterization of the nanoparticles was followed by evaluation of zeta potential, pH, size and polydispersion. The techniques employed included transmission electron microscopy, differential scanning calorimetry and Fourier transform infrared spectroscopy. The formulation presented a size distribution of 635 +/- 12 nm, polydispersion of 0.518, zeta potential of -22.8 +/- 2.3 mV and association efficiency of 74.2%. There were significant differences between the release profiles of free paraquat and the herbicide associated with the alginate/chitosan nanoparticles. Tests showed that soil sorption of paraquat, either free or associated with the nanoparticles. was dependent on the quantity of organic matter present. The results presented in this work show that association of paraquat with alginate/chitosan nanoparticles alters the release profile of the herbicide, as well as its interaction with the soil, indicating that this system could be an effective means of reducing negative impacts caused by paraquat. (C) 2011 Elsevier B.V. All rights reserved.

Desenvolvimento de uma nanoformulação autoemulsificante contendo o alcaloide epiisopiloturina para melhorar sua biodisponibilidade plasmática após administração via oral

Dissertação (mestrado)—Universidade de Brasília, Instituto de Ciências Biológicas, Programa de Pós-Graduação em Nanociência e Nanobiotecnologia, 2016.

Pharmacokinetic profile of two different pharmaceutical forms of theophylline (a slow release tablet and a syrup) after multiple dose administration to healthy human volunteers

Due to the narrow therapeutic range of theophyline, plasma concentrations of this drug are monitored in patients undergoing chronic therapy. Slow-release preparations avoid the fluctuations in plasma levels and improve patient compliance. In this study, we have compared the pharmacokinetic profiles of a theophylline slow-release tablet and a syrup form, when administered in multiple doses to healthy adult volunteers. The classification based upon releasing patterns is confirmed.

Sensitization Prevalence, Antibody Cross-Reactivity and Immunogenic Peptide Profile of Api g 2, the Non-Specific Lipid Transfer Protein 1 of Celery

Background: Celery (Apium graveolens) represents a relevant allergen source that can elicit severe reactions in the adult population. To investigate the sensitization prevalence and cross-reactivity of Api g 2 from celery stalks in a Mediterranean population and in a mouse model. Methodology: 786 non-randomized subjects from Italy were screened for IgE reactivity to rApi g 2, rArt v 3 (mugwort pollen LTP) and nPru p 3 (peach LTP) using an allergen microarray. Clinical data of 32 selected patients with reactivity to LTP under investigation were evaluated. Specific IgE titers and cross-inhibitions were performed in ELISA and allergen microarray. Balb/c mice were immunized with purified LTPs; IgG titers were determined in ELISA and mediator release was examined using RBL-2H3 cells. Simulated endolysosomal digestion was performed using microsomes obtained from human DCs. Results: IgE testing showed a sensitization prevalence of 25.6% to Api g 2, 18.6% to Art v 3, and 28.6% to Pru p 3 and frequent co-sensitization and correlating IgE-reactivity was observed. 10/32 patients suffering from LTP-related allergy reported symptoms upon consumption of celery stalks which mainly presented as OAS. Considerable IgE cross-reactivity was observed between Api g 2, Art v 3, and Pru p 3 with varying inhibition degrees of individual patients' sera. Simulating LTP mono-sensitization in a mouse model showed development of more congruent antibody specificities between Api g 2 and Art v 3. Notably, biologically relevant murine IgE cross-reactivity was restricted to the latter and diverse from Pru p 3 epitopes. Endolysosomal processing of LTP showed generation of similar clusters, which presumably represent T-cell peptides. Conclusions: Api g 2 represents a relevant celery stalk allergen in the LTP-sensitized population. The molecule displays common B cell epitopes and endolysosomal peptides that encompass T cell epitopes with pollen and plant-food derived LTP.

Remote sensing the vertical profile of cloud droplet effective radius, thermodynamic phase, and temperature

Cloud-aerosol interaction is a key issue in the climate system, affecting the water cycle, the weather, and the total energy balance including the spatial and temporal distribution of latent heat release. Information on the vertical distribution of cloud droplet microphysics and thermodynamic phase as a function of temperature or height, can be correlated with details of the aerosol field to provide insight on how these particles are affecting cloud properties and their consequences to cloud lifetime, precipitation, water cycle, and general energy balance. Unfortunately, today's experimental methods still lack the observational tools that can characterize the true evolution of the cloud microphysical, spatial and temporal structure in the cloud droplet scale, and then link these characteristics to environmental factors and properties of the cloud condensation nuclei. Here we propose and demonstrate a new experimental approach (the cloud scanner instrument) that provides the microphysical information missed in current experiments and remote sensing options. Cloud scanner measurements can be performed from aircraft, ground, or satellite by scanning the side of the clouds from the base to the top, providing us with the unique opportunity of obtaining snapshots of the cloud droplet microphysical and thermodynamic states as a function of height and brightness temperature in clouds at several development stages. The brightness temperature profile of the cloud side can be directly associated with the thermodynamic phase of the droplets to provide information on the glaciation temperature as a function of different ambient conditions, aerosol concentration, and type. An aircraft prototype of the cloud scanner was built and flew in a field campaign in Brazil. The CLAIM-3D (3-Dimensional Cloud Aerosol Interaction Mission) satellite concept proposed here combines several techniques to simultaneously measure the vertical profile of cloud microphysics, thermodynamic phase, brightness temperature, and aerosol amount and type in the neighborhood of the clouds. The wide wavelength range, and the use of multi-angle polarization measurements proposed for this mission allow us to estimate the availability and characteristics of aerosol particles acting as cloud condensation nuclei, and their effects on the cloud microphysical structure. These results can provide unprecedented details on the response of cloud droplet microphysics to natural and anthropogenic aerosols in the size scale where the interaction really happens.

Prostaglandin E(2)-loaded microspheres as strategy to inhibit phagocytosis and modulate inflammatory mediators release

PGE(2), an arachidonic acid metabolite produced by various type of cells regulates a broad range of physiological activities in the endocrine, cardiovascular, gastrointestinal, and immune systems, and is involved in maintaining the local homeostasis. In the immune system, PGE(2) is mainly produced by APCs and it can suppress the Th1-mediated immune responses. The aim of this study was to develop PGE(2)-loaded biodegradable MS that prolong and sustain the in vivo release of this mediator. An o/w emulsion solvent extraction-evaporation method was chosen to prepare the MS. We determined their diameters, evaluated the in vitro release of PGE(2), using enzyme immunoassay and MS uptake by peritoneal macrophages. To assess the preservation of biological activities of this mediator, we determined the effect of PGE(2) released from MS on LPS-induced TNF-alpha release by murine peritoneal macrophages. We also analyzed the effect of encapsulated PGE(2) on inflammatory mediators release from HUVECs. Finally, we studied the effect of PGE(2) released from biodegradable MS in sepsis animal model. The use of this formulation can provide an alternative strategy for treating infections, by modulating or inhibiting inflammatory responses, especially when they constitute an exacerbated profile. (C) 2008 Elsevier B.V. All rights reserved.