Nanoparticles incorporating pH-responsive surfactants as a viable approach to improve the intracellular drug delivery

The pH-responsive delivery systems have brought newadvances in the field of functional nanodevices and might allow more accurate and controllable delivery of specific cargoes, which is expected to result in promising applications in different clinical therapies. Here we describe a family of chitosan TPP (tripolyphosphate) nanoparticles (NPs) for intracellular drug delivery, which were designed using two pH-sensitive amino acid-based surfactants fromthe family Nα,Nε-dioctanoyl lysine as bioactive compounds. Lowand mediummolecularweight chitosan (LMW-CS and MMW-CS, respectively) were used for NP preparation, and it was observed that the size distribution for NPs with LMW-CS were smaller (~168 nm) than that for NPs prepared with MMW-CS (~310 nm). Hemolysis assay demonstrated the pH-dependent biomembrane disruptional capability of the constructed NPs. The nanostructures incorporating the surfactants cause negligible membrane permeabilization at pH 7.4. However, at acidic pH, prevailing in endosomes, membrane-destabilizing activity in an erythrocyte lysis assay became evident. When pH decreased to 6.6 and 5.4, hemolytic capability of chitosan NPs increased along with the raise of concentration. Furthermore, studies with cell culture showed that these pH-responsive NPs displayed low cytotoxic effects against 3T3 fibroblasts. The influence of chitosan molecular weight, chitosan to TPP weight ratio, nanoparticle size and nature of the surfactant counterion on the membrane-disruptive properties of nanoparticleswas discussed in detail. Altogether, the results achieved here showed that by inserting the lysine-based amphiphiles into chitosan NPs, pH-sensitive membranolytic and potentially endosomolytic nanocarriers were developed, which, therefore, demonstrated ideal feasibility for intracellular drug delivery

Multifunctional PLGA nanoparticles combining transferrin-targetability and pH-stimuli sensitivity enhanced doxorubicin intracellular delivery and in vitro antineoplastic activity in MDR tumor cells

Targeted delivery aims to enhance cellular uptake and improve therapeutic outcome with higher disease specificity. The expression of transferrin receptor (TfR) is upregulated on tumor cells, which make the protein Tf and its receptor vastly relevant when applied to targeting strategies. Here, we proposed Tf-decorated pH-sensitive PLGA nanoparticles containing the chemosensitizer poloxamer as a carrier for doxorubicin delivery to tumor cells (Tf-DOX-PLGA-NPs), aiming at alleviating multidrug resistance (MDR). We performed a range of in vitro studies to assess whether targeted NPs have the ability to improve DOX antitumor potential on resistant NCI/ADR-RES cells. All evaluations of the Tf-decorated NPs were performed comparatively to the nontargeted counterparts, aiming to evidence the real role of NP surface functionalization, along with the benefits of pH-sensitivity and poloxamer, in the improvement of antiproliferative activity and reversal of MDR. Tf-DOX-PLGA-NPs induced higher number of apoptotic events and ROS generation, along with cell cycle arrest. Moreover, they were efficiently internalized by NCI/ADR-RES cells, increasing DOX intracellular accumulation, which supports the greater cell killing ability of these targeted NPs with respect to MDR cells. Altogether, these findings supported the effectiveness of the Tf-surface modification of DOX-PLGA-NPs for an improved antiproliferative activity. Therefore, our pH-responsive Tf-inspired NPs are a promising smart drug delivery system to overcome MDR effect at some extent, enhancing the efficacy of DOX antitumor therapy

Determination of Methotrexate in pH-Sensitive Chitosan Nanoparticles by Validated RP-LC and UV Spectrophotometric Methods

Nanotechnology-based drug delivery systems are in constant development and, therefore, it is of great importance to have rapid, efficient and accurate analytical methodology to quantify the encapsulated drugs. Here, simple and fast methods, by reversed-phase liquid chromatography (RP-LC) and UV spectrophotometry, were developed and validated for the determination of methotrexate (MTX) in pH-sensitive chitosan nanoparticles (CS-NPs). NPs were prepared using a modified ionotropic complexation process, in which was included a surfactant derived from Nα,Nε-dioctanoyl lysine with an inorganic sodium counterion. The RP-LC method was carried out on a Waters XBridgeTM C18 column (250 mm x 4.6 mm I.D., 5μm), with mobile phase consisted of potassium phosphate buffer (0.05 M, pH 3.2): acetonitrile (86:14, v/v), and UV detection set at 303 nm. The analyses of MTX content by the UV method were also accomplished at 303 nm, using 0.1 M sodium hydroxide as diluent. The measurements were linearly correlated with concentration for both methods in the 1 - 30 μg/mL range (r > 0.9999). The specificity tests showed that there was no interference of the NP components on the quantitative analyses. Precision (repeatability and intermediate precision) was demonstrated by a relative standard deviation lower than 1.5%, whereas the accuracy was assessed by the recovery of MTX from sample matrices, given mean value of ~99%. The proposed methods were applied for the analyses of MTX in different batches of NPs, and the results showed non-significant differences (p > 0.05) between the values obtained with both methodologies. Moreover, the RP-LC method was successfully used to determine the drug entrapment efficiency, and to quantify MTX during in vitro release assays and photolytic degradation studies. In conclusion, the validated methods are suitable to assay MTX in pH-sensitive CS-NPs without any interference from the polymer or surfactant

PEGylated and poloxamer-modified chitosan nanoparticles incorporating a lysine-based surfactant for pH-triggered doxorubicin release

The growing demand for efficient chemotherapy in many cancers requires novel approaches in target-delivery technologies. Nanomaterials with pH-responsive behavior appear to have potential ability to selectively release the encapsulated molecules by sensing the acidic tumor microenvironment or the low pH found in endosomes. Likewise, polyethylene glycol (PEG)- and poloxamer-modified nanocarriers have been gaining attention regarding their potential to improve the effectiveness of cancer therapy. In this context, DOX-loaded pH-responsive nanoparticles (NPs) modified with PEG or poloxamer were prepared and the effects of these modifiers were evaluated on the overall characteristics of these nanostructures. Chitosan and tripolyphosphate were selected to form NPs by the interaction of oppositely charged compounds. A pH-sensitive lysine-based amphiphile (77KS) was used as a bioactive adjuvant. The strong dependence of 77KS ionization with pH makes this compound an interesting candidate to be used for the design of pH-sensitive devices. The physicochemical characterization of all NPs has been performed, and it was shown that the presence of 77KS clearly promotes a pH-triggered DOX release. Accelerated and continuous release patterns of DOX from CS-NPs under acidic conditions were observed regardless of the presence of PEG or poloxamer. Moreover, photodegradation studies have indicated that the lyophilization of NPs improved DOX stability under UVA radiation. Finally, cytotoxicity experiments have shown the ability of DOX-loaded CS-NPs to kill HeLa tumor cells. Hence, the overall results suggest that these pH-responsive CS-NPs are highly potent delivery systems to target tumor and intracellular environments, rendering them promising DOX carrier systems for cancer therapy

Inclusion of a pH‑responsive amino acid‑based amphiphile in methotrexate‑loaded chitosan nanoparticles as a delivery strategy in cancer therapy

The encapsulation of antitumor drugs in nanosized systems with pH-sensitive behavior is a promising approach that may enhance the success of chemotherapy in many cancers. The nanocarrier dependence on pH might trigger an efficient delivery of the encapsulated drug both in the acidic extracellular environment of tumors and, especially, in the intracellular compartments through disruption of endosomal membrane. In this context, here we reported the preparation of chitosan-based nanoparticles encapsulating methotrexate as a model drug (MTX-CS-NPs), which comprises the incorporation of an amino acid-based amphiphile with pH-responsive properties (77KS) on the ionotropic complexation process. The presence of 77KS clearly gives a pH-sensitive behavior to NPs, which allowed accelerated release of MTX with decreasing pH as well as pH-dependent membrane-lytic activity. This latter performance demonstrates the potential of these NPs to facilitate cytosolic delivery of endocytosed materials. Outstandingly the cytotoxicity of MTX-loaded CS-NPs was higher than free drug to MCF-7 tumor cells and, to a lesser extent, to HeLa cells. Based on the overall results, MTX-CS-NPs modified with the pH-sensitive surfactant 77KS could be potentially useful as a carrier system for intracellular drug delivery and, thus, a promising targeting anticancer chemotherapeutic agent

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Anais do V Encontro Brasileiro de Educomunicação: Educação midiática e políticas públicas

A presente coletânea, que chega ao público através de um suporte digital, tem como objetivo disponibilizar os papers, bem como os relatos de experiências educomunicativas apresentados durante o V ENCONTRO BRASILEIRO DE EDUCOMUNICAÇÃO, que teve como tema central: “Educação Midiática e Políticas Públicas”. O evento foi realizado em São Paulo, entre 19 e 21 de setembro de 2013, a partir de uma parceria entre o NCE/USP - Núcleo de Comunicação e Educação da USP, a Licenciatura em Educomunicação da ECA/USP, a ABPEducom – Associação Brasileira de Pesquisadores e Profissionais da Educomunicação e a FAPCOM – Faculdade Paulus de Tecnologia e Comunicação, que ofereceu seu campus, na Vila Mariana, para os atos do evento. Os presentes anais disponibilizam o texto de abertura, de autoria do coordenador geral do evento, denominado “Educação midiática e políticas públicas: vertentes históricas da emergência da Educomunicação na América Latina”. Na sequência, apresentam 61 papers sobre aspectos específicos da temática geral, resultantes de pesquisas na área, seguidos de 27 relatos de práticas educomunicativas, em nível nacional

ATLANTIC EPIPHYTES: a data set of vascular and non-vascular epiphyte plants and lichens from the Atlantic Forest

Epiphytes are hyper-diverse and one of the frequently undervalued life forms in plant surveys and biodiversity inventories. Epiphytes of the Atlantic Forest, one of the most endangered ecosystems in the world, have high endemism and radiated recently in the Pliocene. We aimed to (1) compile an extensive Atlantic Forest data set on vascular, non-vascular plants (including hemiepiphytes), and lichen epiphyte species occurrence and abundance; (2) describe the epiphyte distribution in the Atlantic Forest, in order to indicate future sampling efforts. Our work presents the first epiphyte data set with information on abundance and occurrence of epiphyte phorophyte species. All data compiled here come from three main sources provided by the authors: published sources (comprising peer-reviewed articles, books, and theses), unpublished data, and herbarium data. We compiled a data set composed of 2,095 species, from 89,270 holo/hemiepiphyte records, in the Atlantic Forest of Brazil, Argentina, Paraguay, and Uruguay, recorded from 1824 to early 2018. Most of the records were from qualitative data (occurrence only, 88%), well distributed throughout the Atlantic Forest. For quantitative records, the most common sampling method was individual trees (71%), followed by plot sampling (19%), and transect sampling (10%). Angiosperms (81%) were the most frequently registered group, and Bromeliaceae and Orchidaceae were the families with the greatest number of records (27,272 and 21,945, respectively). Ferns and Lycophytes presented fewer records than Angiosperms, and Polypodiaceae were the most recorded family, and more concentrated in the Southern and Southeastern regions. Data on non-vascular plants and lichens were scarce, with a few disjunct records concentrated in the Northeastern region of the Atlantic Forest. For all non-vascular plant records, Lejeuneaceae, a family of liverworts, was the most recorded family. We hope that our effort to organize scattered epiphyte data help advance the knowledge of epiphyte ecology, as well as our understanding of macroecological and biogeographical patterns in the Atlantic Forest. No copyright restrictions are associated with the data set. Please cite this Ecology Data Paper if the data are used in publication and teaching events. © 2019 The Authors. Ecology © 2019 The Ecological Society of Americ