Surface assembly of poly(I:C) on PEGylated microspheres to shield from adverse interactions with fibroblasts.

By expressing an array of pattern recognition receptors (PRRs), fibroblasts play an important role in stimulating and modulating the response of the innate immune system. The TLR3 ligand polyriboinosinic acid-polyribocytidylic acid, poly(I:C), a mimic of viral dsRNA, is a vaccine adjuvant candidate to activate professional antigen presenting cells (APCs). However, owing to its ligation with extracellular TLR3 on fibroblasts, subcutaneously administered poly(I:C) bears danger towards autoimmunity. It is thus in the interest of its clinical safety to deliver poly(I:C) in such a way that its activation of professional APCs is as efficacious as possible, whereas its interference with non-immune cells such as fibroblasts is controlled or even avoided. Complementary to our previous work with monocyte-derived dendritic cells (MoDCs), here we sought to control the delivery of poly(I:C) surface-assembled on microspheres to human foreskin fibroblasts (HFFs). Negatively charged polystyrene (PS) microspheres were equipped with a poly(ethylene glycol) (PEG) corona through electrostatically driven coatings with a series of polycationic poly(L-lysine)-graft-poly(ethylene glycol) copolymers, PLL-g-PEG, of varying grafting ratios g from 2.2 up to 22.7. Stable surface assembly of poly(I:C) was achieved by incubation of polymer-coated microspheres with aqueous poly(I:C) solutions. Notably, recognition of both surface-assembled and free poly(I:C) by extracellular TLR3 on HFFs halted their phagocytic activity. Ligation of surface-assembled poly(I:C) with extracellular TLR3 on HFFs could be controlled by tuning the grafting ratio g and thus the chain density of the PEG corona. When assembled on PLL-5.7-PEG-coated microspheres, poly(I:C) was blocked from triggering class I MHC molecule expression on HFFs. Secretion of interleukin (IL)-6 by HFFs after exposure to surface-assembled poly(I:C) was distinctly lower as compared to free poly(I:C). Overall, surface assembly of poly(I:C) may have potential to contribute to the clinical safety of this vaccine adjuvant candidate.

Thrombin-sensitive photodynamic agents: a novel strategy for selective synovectomy in rheumatoid arthritis.

Protease-sensitive macromolecular prodrugs have attracted interest for bio-responsive drug delivery to sites with up-regulated proteolytic activities such as inflammatory or cancerous lesions. Here we report the development of a novel polymeric photosensitizer prodrug (T-PS) to target thrombin, a protease up-regulated in synovial tissues of rheumatoid arthritis (RA) patients, for minimally invasive photodynamic synovectomy. In T-PS, multiple photosensitizer units are tethered to a polymeric backbone via short, thrombin-cleavable peptide linkers. Photoactivity of the prodrug is efficiently impaired due to energy transfer between neighbouring photosensitizer units. T-PS activation by exogenous and endogenous thrombin induced an increase in fluorescence emission by a factor of 16 after in vitro digestion and a selective fluorescence enhancement in arthritic lesions in vivo, in a collagen-induced arthritis mouse model. In vitro studies on primary human synoviocytes showed a phototoxic effect only after enzymatic digestion of the prodrug and light irradiation, thus demonstrating the functionality of T-PS induced PDT. The developed photosensitizer prodrugs combine the passive targeting capacity of macromolecular drug delivery systems with site-selective photosensitizer release and activation. They illuminate lesions with pathologically enhanced proteolytic activity and induce cell death, subsequent to irradiation.

Atorvastatin-loaded hydrogel affects the smooth muscle cells of human veins.

Intimal hyperplasia (IH) is the major cause of stenosis of vein grafts. Drugs such as statins prevent stenosis, but their systemic administration has limited effects. We developed a hyaluronic acid hydrogel matrix, which ensures a controlled release of atorvastatin (ATV) at the site of injury. The release kinetics demonstrated that 100% of ATV was released over 10 hours, independent of the loading concentration of the hydrogel. We investigated the effects of such a delivery on primary vascular smooth muscle cells isolated from human veins. ATV decreased the proliferation, migration, and passage of human smooth muscle cells (HSMCs) across a matrix barrier in a similar dose-dependent (5-10 µM) and time-dependent manner (24-72 hours), whether the drug was directly added to the culture medium or released from the hydrogel. Expression analysis of genes known to be involved in the development of IH demonstrated that the transcripts of both the gap junction protein connexin43 (Cx43) and plasminogen activator inhibitor-1 (PAI-1) were decreased after a 24-48-hour exposure to the hydrogel loaded with ATV, whereas the transcripts of the heme oxygenase (HO-1) and the inhibitor of tissue plasminogen activator were increased. At the protein level, Cx43, PAI-1, and metalloproteinase-9 expression were decreased, whereas HO-1 was upregulated in the presence of ATV. The data demonstrate that ATV released from a hydrogel has effects on HSMCs similar to the drug being freely dissolved in the environment.

Estudo da influência da natureza de reticulantes e aditivos orgânicos sobre o comportamento de géis de quitosana

The physical-chemical process of swelling in water-based gel of natural polymers is investigated with the purpose of applying these systems to biomedical materials for controlled release of drugs. In this work we develop a study about the sol-gel transition of solutions of chitosan in the presence of formaldehyde and glutaraldehyde like crosslinking agents and we have determined the effect of many aditives in the time of gelification from the elaborated sistems. The phisical-chemistry process of swelling of the formed gels was evaluated in function of the degree of crosslinking of the incorporated aditives and the pH. Gelling times of chitosan solutions were obtained using viscosimetric measurement, in the pre-gel state, as well as condutivity ones.The results obtained suggest that component concentration modifies the kinetic profile of the transition and the swelling behavior. Regarding H+ content, the gels were highly susceptible to swelling in acidic conditions, which characterize this system as pH - sensitive.

Modificação química de argilas: desafios científicos e tecnológicos para obtenção de novos produtos com maior valor agregado

Chemical modification of clays is possible due to their ion-exchange and adsorption capacities, which allows the adjustment of the physicochemical properties of the surfaces of their layers. This modification makes possible the use of clays to produce a great number of new materials, which range from coarse applications such as oil based drilling fluids to refined applications such as pharmaceutical products. This article intends to expose where there is still space for research and investment aiming at the performance improvement of clay-based materials.

Correlação entre parâmetros da cinética de intumescimento com características estruturais e hidrofílicas de hidrogéis de poliacrilamida e metilcelulose

In this paper, the effects of acrylamide (AAm), methylcellulose (MC) contents, pH and ionic strength on kinetic, network and hydrophilic properties of polyacrylamide and methylcellulose hydrogels were investigated. The hydrogels were characterized by evaluating of network [average molecular weight between crosslinks (M C), crosslink density (q) and the number of elastically effective chains (Ve)], and kinetic parameters [diffusional exponent (n), diffusion constant (k) and diffusion coefficient (D)]. Such properties were controlled by adjusting of the AAm, MC contents, pH and ionic strength factors. Due to high hydrophilicity and fast water-uptake, the PAAm-MC hydrogels can be considered as materials for potential applications in agricultural fields, mainly in controlled release of water or pesticides.

Formulações de atrazina em xerogéis: síntese e caracterização

In this study, controlled release formulations of Atrazine (ATZ) were synthesized by the sol-gel method and characterized by elemental, FTIR, SEM, BET and DSC analyses. The release kinetic of ATZ from the formulations in CaCl2 0.01 mol L-1 medium was monitored by UV/Vis spectroscopy. In all formulations, ATZ was physically dispersed on the Si-polymer, and the dispersion grade decreased with increasing amount of herbicide. The ATZ release kinetics was controlled mainly by dissolution, and the data could be fitted to the Korsmeyer - Pepper model. The ATZ as xerogel presents a lower affinity for soil than as granulated form.

Produção de micropartículas de alginato contendo Flavobacterium columnare inativada pelo método de emulsão para vacinação de peixes por via oral

Alginate microparticles were prepared by an emulsion method aiming oral controlled release of antigens to fish. The effects of emulsification temperature and impeller type on particle morphology, average diameter, and size distribution were evaluated. Microparticles contaning formalin-killed Flavobacterium columnare cells (a model antigen) were prepared and characterized regarding bacterial release and particle stability when exposed to Nile tilapia (Oreochromis niloticus) typical gastrointestinal conditions. This methodology allowed the production of microparticles containing up to 14.3 g/L of bacterin, stable at a pH range from 2.0 to 9.0 for 12 h and smaller than 35 μm.

Aplicação de ciclodextrinas em processos têxteis

Cyclodextrins (CDs) are water soluble cyclic sugars with a hydrophobic nanometric cavity that permits the formation of host/guest inclusion complexes with a large variety of molecules, alternating their physical-chemical properties. In the present review CD research related to the processing of textiles is revised and discussed. CDs may function as encapsulating, dispersing and levelling agents in the dyeing and washing of textiles. Furthermore they may be anchored to polymers and textile fibers in order to impart special properties such as odor reduction, UV protection or for the controlled release of perfumes, aromas, mosquito repellents or substances with therapeutical effects.

Avaliação da liberação de NH4NO3 ocluido em zeólita 4A a partir de soluções salinas

The zeolite 4A was used to evaluate the thermo kinetics parameters of NH4+ and NO3- ions occluded in its structure. The Osawa method for activation energy calculation was used to evaluate its thermal stability, and the results shown that the ion species interact differently depending on the zeolite pores, which determines the controlled release by its structure.

Evaluation of chitosan microparticles containing curcumin and crosslinked with sodium tripolyphosphate produced by spray drying

The aim of this study was to encapsulate curcumin into chitosan, using sodium tripolyphosphate (TPP) as an ionic crosslinker by the spray drying method. The influence of TPP on the properties of the final product, such as solubility, morphology, loading efficiency, thermal behavior, swelling degree and release profiles, was evaluated. The microparticles had a spherical morphology (0.5-20 µm) with no apparent porosity or cracks. Results indicated the formation of a polymeric network, which ensures effective protection for curcumin. Controlled-release studies were carried out at pH 1.2 and 6.8, to observe the influence of pH on curcumin release while the mechanism was analyzed using the Korsmeyer-Peppas equation.

Desenvolvimento e caracterização de nanopartículas lipídicas destinadas à aplicação tópica de dapsona

In this work, theospheres (innovative lipid nanoparticles) were prepared by the high pressure homogenization technique using different surfactants for dapsone encapsulation. Mean particle size ranged from 105 to 153 nm and negative zeta potentials were obtained for all theosphere formulations. Atomic force microscopy images confirmed the spherical shape of theospheres. The HPLC method used to determine dapsone-loaded theospheres was selective, linear, exact and precise. The entrapment efficiency of dapsone was 91.4%. Theospheres provided controlled release of idebenone (52.7 ± 1.6%) in comparison to the free drug (103.1 ± 1.9%).

Estudo da liberação controlada do herbicida ametrina em compósitos à base de PVA: carvão ativado

Herbicides have great importance in agricultural productivity for weed control, given their competition with crops. However, inadequate application of herbicides may lead to environmental problems, which can be minimized through controlled release of the active compounds. This may be achieved by protecting the herbicide in a structure with adequate porosity, where the diffusional behavior can determine release. Thus, in this study we evaluated a novel structure, a composite based on activated carbon bonded by polyvinyl alcohol (PVA) as pellets, to deliver a triazine herbicide. The product obtained was shown to be adequate for its purpose, since it was possible to process regular pellets, where the PVA percentage determined the properties.

DEVELOPMENT AND VALIDATION OF ANALYTICAL METHOD FOR PALM OIL DETERMINATION IN MICROCAPSULES PRODUCED BY COMPLEX COACERVATION

The microencapsulation of palm oil may be a mechanism for protecting and promoting the controlled release of its bioactive compounds. To optimize the microencapsulation process, it is necessary to accurately quantify the palm oil present both external and internal to the microcapsules. In this study, we developed and validated a spectrophotometric method to determine the microencapsulation efficiency of palm oil by complex coacervation. We used gelatin and gum arabic (1:1) as wall material in a 5% concentration (w/v) and palm oil in the same concentration. The coacervates were obtained at pH 4.0 ± 0.01, decanted for 24 h, frozen (−40 ºC), and lyophilized for 72 h. Morphological analyzes were then performed. We standardized the extraction of the external palm oil through five successive washes with an organic solvent. We then explored the best method for rupturing the microcapsules. After successive extractions with hexane, we determined the amount of palm oil contained in the microcapsules using a spectrophotometer. The proposed method was shown to be of low cost, fast, and easy to implement. In addition, in the validation step, we confirmed the method to be safe and reliable, as it proved to be specific, accurate, precise, and robust.

Atrazine persistence applied as commercial and xerogel formulations in oxisol

The intensive use of pesticides have contaminated the soil and groundwater. The application of herbicides as controlled release formulations may reduce the environmental damage related to their use because it may optimize the efficiency of the active ingredient and reducing thus the recommended dose. The objective of this study was to evaluate the persistence of the herbicide atrazine applied as commercial formulation (COM) and as controlled release formulation (xerogel - XER) in Oxisol. The experimental design used was split-plot randomized-blocks with four replications, in a (2 x 6) + 1 arrangement. The two formulations (COM and XER) were assigned to main plots and different atrazine concentrations (0, 3.200, 3.600, 4.200, 5.400 and 8.000 g atrazine ha-1) were assigned to sub-plots. Persistence was determined by means of dissipation kinetics and bioavailability tests. The methodology of bioassays to assess the atrazine availability is efficient and enables to distinguish the tested formulations. The availability of atrazine XER is higher than the commercial in two different periods: up to 5 days after herbicide application and at the 35th day after application. The XER formulation tends to be more persistent in relation to COM formulation.