Hybrid molecules of protoflavones and spirooxindole derivatives with selective cytotoxicity against triple-negative breast cancer cells.

The combination of compounds with complementary bioactivities into hybrid molecules is an emerging concept in drug discovery. In this study, we aimed to synthesize new hybrid compounds based on p53-MDM2/X protein-protein interaction spiropyrazoline oxindole-based inhibitors and ataxia telangiectasia and Rad3-related (ATR) protoflavone-based inhibitors through copper(i) catalysed azide-alkyne cycloaddition. Five new hybrids were prepared along with three representative reference fragments.

Infliximab microencapsulation: an innovative approach for intra-articular administration of biologics in the management of rheumatoid arthritis-in vitro evaluation.

Microencapsulation of the therapeutical monoclonal antibody infliximab (INF) was investigated as an innovative approach to improve its stability and to achieve formulations with convenient features for intra-articular administration. Ultrasonic atomization (UA), a novel alternative to microencapsulate labile drugs, was compared with the conventional emulsion/evaporation method (Em/Ev) using biodegradable polymers, specifically Polyactive 1000PEOT70PBT30 [poly(ethylene-oxide-terephthalate)/poly(butylene-terephthalate); PEOT-PBT] and its polymeric blends with poly-(D, L-lactide-co-glycolide) (PLGA) RG502 and RG503 (PEOT-PBT:PLGA; 65:35). Six different formulations of spherical core-shell microcapsules were successfully developed and characterized.

Topical Administration of a Nanoformulation of Chitosan-Hyaluronic Acid-Epoetin Beta in a Rat Model of Glaucoma.

The present work investigates the effects of chitosan-hyaluronic acid-epoetin beta (CS/HA-EPOβ) nanoparticles after topical ocular administration in a rat glaucoma model. Wistar Hannover rats ( = 24) were submitted to a complete ophthalmological examination and electroretinography, followed by glaucoma induction in their right eye on day 1 of the study. Treatment group (T) received CS/HA-EPOβ nanocarriers ( = 12), while the control group (C) received only empty ones.

Design and Characterization of an Ethosomal Gel Encapsulating Rosehip Extract.

Rising environmental awareness drives green consumers to purchase sustainable cosmetics based on natural bioactive compounds. The aim of this study was to deliver L. extract as a botanical ingredient in an anti-aging gel using an eco-friendly approach.

Topical ocular delivery of nanoparticles with epoetin beta in Wistar Hannover rats.

Topical instillation of drugs targeting the posterior ocular segment is an expanding area of research. Chitosan and hyaluronic acid have remarkable mucoadhesive properties and potentially enhance pre-corneal retention time after topical instillation. Bearing this in mind, we explored the possibility of delivering epoetin beta (EPOβ) to the posterior segment of the eye in a chitosan-hyaluronic acid (CS/HA-EPOβ) nanoparticulate system using the topical route of administration.

Comparison of the Role of Different Levels of Religiousness and Spirituality in Controversial Ethical Issues and Clinical Practice among Brazilian Resident Physicians: Results from the Multicenter SBRAMER Study.

This study compares clinical practice and objections to controversial ethical issues among 836 Brazilian resident physicians according to levels of religiousness/spirituality. Residents with low religiousness/spirituality (s/r) believed less in the influence of spirituality on clinical practice, were less comfortable addressing this issue, tended to listen less carefully and try to change the subject more than other groups. Residents with high spirituality and low religiousness (S/r) inquired more about religious/spiritual issues, while those with high religiousness/spirituality (S/R) were more supportive and reported fewer barriers to addressing these issues.

New Peptide Functionalized Nanostructured Lipid Carriers with CNS Drugs and Evaluation Anti-proliferative Activity.

Nanoparticulate systems have been widely investigated as delivery vectors for efficient drug delivery in different diseases. Nanostructured lipid carriers (NLC) are composed of both solid and liquid lipids (glyceryl dibehenate and diethylene glycol monoethyl ether) and have demonstrated enhanced biological compatibility and increased drug loading capability. Furthermore, the use of peptides, in particular cell-penetrating peptides, to functionalize nanoparticles and enhance cell membrane permeation was explored in this paper.

Trends in the Design and Evaluation of Polymeric Nanocarriers: The In Vitro Nano-Bio Interactions.

Different types of natural and synthetic polymeric nanocarriers are being tested for diverse biomedical applications ranging from drug/gene delivery vehicles to imaging probes. The development of such innovative nanoparticulate systems (NPs) should include in the very beginning of their conception a comprehensive evaluation of the nano-bio interactions. Specifically, intrinsic physicochemical properties as size, surface charge and shape may have an impact on cellular uptake, intracellular trafficking, exocytosis and cyto- or genocompatibility.

Development of Neuropeptide Y and Cell-Penetrating Peptide MAP Adsorbed onto Lipid Nanoparticle Surface.

Functionalization of nanoparticles surfaces have been widely used to improve diagnostic and therapeutic biological outcome. Several methods can be applied to modify nanoparticle surface; however, in this article we focus toward a simple and less time-consuming method. We applied an adsorption method on already formulated nanostructured lipid carriers (NLC) to functionalize these nanoparticles with three distinct peptides sequences.

Chitosan and Hyaluronic Acid Nanoparticles as Vehicles of Epoetin Beta for Subconjunctival Ocular Delivery.

Neuroprotection in glaucoma using epoetin beta (EPOβ) has yielded promising results. Our team has developed chitosan-hyaluronic acid nanoparticles (CS/HA) designed to carry EPOβ into the ocular globe, improving the drug's mucoadhesion and retention time on the ocular surface to increase its bioavailability. In the present in vivo study, we explored the possibility of delivering EPOβ to the eye through subconjunctival administration of chitosan-hyaluronic acid-EPOβ (CS/HA-EPOβ) nanoparticles.

Investigation of the genotoxicity of digested titanium dioxide nanomaterials in human intestinal cells.

The widespread use of titanium dioxide nanomaterials (TiO NMs) in food and consumer products such as toothpaste or food contact materials, suggests the relevance of human oral exposure to these nanomaterials (NMs) and raises the possibility of adverse effects in the gastrointestinal tract (GIT). We previously showed that the in vitro digestion of TiO NMs may increase their toxicity in intestinal cells. In this work, we analyzed the genotoxicity and the intracellular reactive oxygen species induction by physiologically relevant concentrations of three different TiO NMs (NM-102, NM-103 and NM-105) in Caco-2 and HT29-MTX-E12 intestinal cells, while considering the potential influence of the digestion process in the NMs' physiochemical characteristics.

Tryptophanol-Derived Oxazolopyrrolidone Lactams as Potential Anticancer Agents against Gastric Adenocarcinoma.

Gastric cancer is one of the deadliest cancers in modern societies, so there is a high level of interest in discovering new drugs for this malignancy. Previously, we demonstrated the ability of tryptophanol-derived polycyclic compounds to activate the tumor suppressor protein p53, a relevant therapeutic target in cancer. In this work, we developed a novel series of enantiomerically pure tryptophanol-derived small molecules to target human gastric adenocarcinoma (AGS) cells.

3D-printed platform multi-loaded with bioactive, magnetic nanoparticles and an antibiotic for re-growing bone tissue.

Polymeric platforms obtained by three-dimensional (3D) printing are becoming increasingly important as multifunctional therapeutic systems for bone treatment applications. In particularly, researchers aim to control bacterial biofilm on these 3D-platforms and enhance re-growing bone tissue, at the same time. This study aimed to fabricate a 3D-printed polylactic acid platform loaded with hydroxyapatite (HA), iron oxide nanoparticles (IONPs) and an antibiotic (minocycline) with tuneable properties and multistimuli response.

Solid Lipid Nanoparticles and Nanostructured Lipid Carriers as Smart Drug Delivery Systems in the Treatment of Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most common and malignant type of brain tumor. In fact, tumor recurrence usually appears a few months after surgical resection and chemotherapy, mainly due to many factors that make GBM treatment a real challenge, such as tumor location, heterogeneity, presence of the blood-brain barrier (BBB), and others. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) represent the most promising carriers for therapeutics delivery into the central nervous system (CNS) owing to their inherent ability to cross the BBB.

Religiosity and Spirituality of Resident Physicians and Implications for Clinical Practice-the SBRAMER Multicenter Study.

Objectives: To assess the attitudes, knowledge, and experiences of Brazilian resident physicians regarding religiosity/spirituality (R/S), factors associated with addressing this issue, and its influence on clinical practice.

Methods: We report results of the multicenter "Spirituality in Brazilian Medical Residents" (SBRAMER) study involving 7 Brazilian university centers. The Network for Research Spirituality and Health (NERSH) scale (collecting sociodemographic data, opinions about the R/S-health interface, and respondents' R/S characteristics) and the Duke Religion Index were self-administered.

Analysis of the Characteristics and Cytotoxicity of Titanium Dioxide Nanomaterials Following Simulated In Vitro Digestion.

Several metallic nanomaterials (NMs), such as titanium dioxide nanomaterials (TiO), present beneficial properties with a broad range of innovative applications. The human population is exposed to TiO, particularly by ingestion, due to its increasing use as a food additive and inclusion in dietary supplements and food packaging materials. Whether this oral exposure may lead to adverse local or systemic outcomes has been the subject of research, but studies have generated contradictory results, reflecting differences in the physicochemical properties of the TiO studied, effects of the surrounding matrix, and modifications during digestion.

Novel and Modified Neutrophil Elastase Inhibitor Loaded in Topical Formulations for Psoriasis Management.

Human neutrophil elastase (HNE) is a serine protease that degrades matrix proteins. An excess of HNE may trigger several pathological conditions, such as psoriasis. In this work, we aimed to synthesize, characterize and formulate new HNE inhibitors with a 4-oxo-β-lactam scaffold with less toxicity, as well as therapeutic index in a psoriasis context.

3-Oxo-β-sultam as a Sulfonylating Chemotype for Inhibition of Serine Hydrolases and Activity-Based Protein Profiling.

3-Oxo-β-sultams are four-membered ring ambident electrophiles that can react with nucleophiles either at the carbonyl carbon or at the sulfonyl sulfur atoms, and that have been reported to inhibit serine hydrolases via acylation of the active-site serine residue. We have developed a panel of 3-oxo-β-sultam inhibitors and show, through crystallographic data, that they are regioselective sulfonylating electrophiles, covalently binding to the catalytic serine of human and porcine elastases through the sulfur atom. Application of 3-oxo-β-sultam-derived activity-based probes in a human proteome revealed their potential to label disease-related serine hydrolases and proteasome subunits.

L. Extract: A Promising Cosmetic Ingredient with Antioxidant Properties.

L. (), popularly known as wild strawberry, is a plant from the Rosaceae family, found in temperate and subtropical areas of the northern hemisphere. leaves have been shown to have antiseptic, emollient, and dermatological protection properties, due to the presence of bioactive compounds, such as flavonoids, phenolic acids, ellagitannins, and proanthocyanidins.

Synthesis and Characterization of Isosorbide-Based Polyurethanes Exhibiting Low Cytotoxicity Towards HaCaT Human Skin Cells.

The synthesis of four samples of new polyurethanes was evaluated by changing the ratio of the diol monomers used, poly(propylene glycol) (PPG) and D-isosorbide, in the presence of aliphatic isocyanates such as the isophorone diisocyanate (IPDI) and 4,4'-methylenebis(cyclohexyl isocyanate) (HMDI). The thermal properties of the four polymers obtained were determined by DSC, exhibiting values in the range 55⁻70 °C, and their molecular structure characterized by FTIR, ¹H, and C NMR spectroscopies. The diffusion coefficients of these polymers in solution were measured by the Pulse Gradient Spin Echo (PGSE) NMR method, enabling the calculation of the corresponding hydrodynamic radii in diluted solution (1.

Starch-Based Pickering Emulsions as Platforms for Topical Antibiotic Delivery: In Vitro and In Vivo Studies.

The present study investigated a new approach to treat superficial skin infections by topical application of minocycline hydrochloride (MH) formulated in a novel starch-based Pickering emulsion (ASt-emulsions). The emulsions were fully characterized in terms of efficacy, as well as in vitro release and permeation studies. The emulsions provided a prolonged MH release, always above its minimum inhibitory concentration against , although the drug did not permeate through the entire skin layer.

Design and Characterization of a New Quercus Suber-Based Pickering Emulsion for Topical Application.

Quercus Suber Bark from L. is a natural, renewable and biodegradable biomaterial with multifunctional proprieties. In this study, we used it as solid particles to stabilize a Pickering emulsion.

Transfection of pulmonary cells by stable pDNA-polycationic hybrid nanostructured particles.

Aim: Cationically modified solid lipid nanoparticles (SLN) were investigated as plasmid DNA (pDNA) carriers and transfection agents for the pulmonary route.

Materials & Methods: pDNA-loaded SLN were produced using glyceryl dibehenate or tristearate as matrix lipids and chitosan as surface charge modifier, and encapsulated by spray-drying in mannitol and trehalose microspheres.

Results: Nanoparticles of 200 nm, and zeta potential around +15 mV were produced.

Acrylic microparticles increase daptomycin intracellular and in vivo anti-biofilm activity against Staphylococcus aureus.

Daptomycin (DAP) is a cyclic lipopeptide antibiotic with potential clinical application in orthopedic infections caused by staphylococci. However, it failed to eradicate Staphylococcus aureus in vitro, in intracellular infection studies, as well as in vivo in an experimental model of implant-associated biofilm infections. In this study, the antimicrobial effect of DAP encapsulated in poly(methyl methacrylate)-Eudragit (PMMA-EUD) microparticles (DAP-MPs) on intracellular S.

Diazaborines as New Inhibitors of Human Neutrophil Elastase.

Boronic acids (BAs) are a prominent functionality extensively used to design biologically active compounds and functional biomaterials. Boronic acids open shell can lead to unspecific reactivity of BAs with endogenous nucleophiles and to undesired off-target effects. Here, diazaborines are presented as a new class of boron-based warheads for serine proteases inhibition, in which the boron function is stabilized in the form of an aromatic boron-based heterocycle.