Drug release mechanisms of chemically cross-linked albumin microparticles: effect of the matrix erosion

Albumin (BSA) microparticles were developed as a biotechnological alternative for drug delivery. Vitamin B12 (Vit-B12) was used as a model drug. The microparticles were obtained from maleic anhydride-functionalized BSA and N′,N′-dimethylacrylamide (DMAAm) in a W/O emulsion without and with PVA. The microparticles produced at 15 min of stirring without PVA showed the best results in terms of size, homogeneity, and sphericity. In such a case, BSA played a role as a surface active agent, replacing PVA. For longer stirring times, BSA was unable to act as an emulsifier. These microparticles showed an uncommon release profile, consisting of a two-step release mechanism, at the pH range studied. Considering that a two-step release mechanism is occurring, the experimental data were adjusted by applying modified power law and Weibull equations in order to describe release mechanism n and release rate constant k, respectively. Each one of the release stages was related to a specific value of n and k. The second stage was driven by a super case II transport mechanism, as a result of diffusion, macromolecular relaxation, and erosion. A third model, described by Hixson–Crowell, confirmed the erosion mechanism. Vit-B12 diffusion kinetics in aqueous solutions (i.e., without the microparticles) follows a one-step process, being k dependent on the pH, confirming that the two-step release mechanism is a characteristic profile of the developed microparticles. The microparticles released only 2.70% of their initial drug load at pH 2, and 58.53% at pH 10

Distortion of the QRS in elderly patients with myocardial infarction

Background: Distortion of the terminal portion of the QRS in the initial electrocardiogram (ECG) is a strong predictor of adverse outcome in myocardial infarction. Our purpose is to assess the relationship of distortion of QRS and other ECG characteristics with older age. Methods and results: We analysed 634 consecutive patients (age 62.6 &#177; 13.7, 77% male) admitted in the first 12 hours of ST-elevation myocardial infarction. Two groups of age were defined: < 75 years-old and &#8805; 75 years-old. Additionally, we defined two ECG groups according to the presence of ST segment elevation with distortion of the terminal portion of the QRS in two or more adjacent leads (QRS+) or the absence of this pattern (QRS&#8211;). Older people had more often QRS+ (30% vs. 20%, p = 0.023). The older group with QRS+ had an in-hospital mortality of 18%, vs. 7% with QRS&#8211; (p = 0.04), and an incidence of major adverse events of 40% vs. 14% (p = 0.002). In the multivariate analysis, age &#8805; 75 years was an independent predictor of distortion of the QRS (odds ratio 2.1, 1.2&#8211;4.9, p = 0.016). Conclusions: The distortion of the terminal portion of the QRS in myocardial infarction is more frequent in elderly people, and is significantly related to adverse prognosis. This ECG finding can be helpful to promptly stratify the risk in elderly patient

Venous endothelium dysfunction is also presented in hypertensive patients

Univ São Paulo, Sch Med, Inst Heart, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

Morphology of temperature-sensitive and ph-responsive ipn-hydrogels for application as biomaterial for cell growth

In the present investigation, hydrogels with pH-responsive and temperature-sensitive properties were obtained by formation of alginate-Ca network inside the PNIPAAm network resulting in an interpenetrated network system (IPN). From scanning electron microscopy (SEM) images and water uptake (WU) tests one observed that IPN hydrogels exhibited a drastic shrinking when heated above 30-35 ºC. The shrinking resulted in decreased average pore size, thus affect the hydrogel morphology significantly. In the pH range studied, IPN hydrogels showed significant pH dependence, which was attributed to the charged alginate groups. The results indicated that the pH-responsiveness and temperature-dependence of alginate and PNIPAAm, respectively, were preserved in IPN hydrogels. In addition, such hydrogels become less deformable when subjected to compressive stress. These hydrogels presented porous morphology that may be tuned by controlling the temperature, and this makes them attractive for applications as biomaterial in cell growth.No presente trabalho, foram sintetizados hidrogéis com ambas as propriedades, termo-sensíveis e pH-responsivos, pela formação de redes de alginato de cálcio (alginato-Ca) dentro de redes de poli(N-Isopropil Acrilamida) (PNIPAAm), resultando em um sistema IPN (sistema de redes poliméricas interpenetradas). Através das análises por microscopia de varredura eletrônica (MEV) e ensaios de intumescimento foi possível observar que os hidrogéis IPN exibiram forte contração quando aquecidos acima da LCST (temperatura critica inferior de solubilização) da PNIPAAm, ou seja, acima de temperaturas de 30-35 ºC. Observou-se ainda que devido à contração do hidrogel, houve uma diminuição significativa nos tamanhos de poros os quais foram observados pelas micrografias. Observou-se também que no intervalo de pH estudado os hidrogéis de IPN sofreram significativa variação da estrutura com a variação desse parâmetro. Tal efeito foi atribuído à presença de grupos químicos carregados com alginato, os quais possuem carga elétrica negativa. Os resultados indicaram que o hidrogel formado por alginato-Ca e PNIPAAm possuíram características especificas após variação de pH e temperatura, e que tais características são derivadas dos compostos individuais envolvidos na síntese. Nesse caso, as propriedades de alginato-Ca e PNIPAAm livres foram preservadas dentro do hidrogel. Tal hidrogel ficou mais resistente à aplicação de uma tensão de compressão. Como conclusão, observou-se que os hidrogéis apresentaram morfologia característica para variações controladas de pH e temperatura, podendo ser eficientemente aplicados como biomaterial na cultura de células.105110Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Bradykinin or Acetylcholine as Vasodilators to Test Endothelial Venous Function in Healthy Subjects

INTRODUCTION: The evaluation of endothelial function has been performed in the arterial bed, but recently evaluation within the venous system has also been explored. Endothelial function studies employ different drugs that act as endothelium-dependent vasodilatory response inductors. OBJECTIVES: The aim of this study is to compare the endothelium-dependent venous vasodilator response mediated by either acetylcholine or bradykinin in healthy volunteers. METHODS AND RESULTS: Changes in vein diameter after phenylephrine-induced venoconstriction were measured to compare venodilation induced by acetylcholine or bradykinin (linear variable differential transformer dorsal hand vein technique). We studied 23 healthy volunteers; 31% were male, and the subject had a mean age of 33 ± 8 years and a mean body mass index of 23 ± 2 kg/m2. The maximum endothelium-dependent venodilation was similar for both drugs (p = 0.13), as well as the mean responses for each dose of both drugs (r = 0.96). The maximum responses to acetylcholine and bradykinin also had good agreement. CONCLUSION: There were no differences between acetylcholine and bradykinin as venodilators in this endothelial venous function investigation

Cannabinoid receptor CB2 ablation protects against TAU induced neurodegeneration.

Tauopathies are a group of neurodegenerative diseases characterized by the alteration/aggregation of TAU protein, for which there is still no effective treatment. Therefore, new pharmacological targets are being sought, such as elements of the endocannabinoid system (ECS). We analysed the occurrence of changes in the ECS in tauopathies and their implication in the pathogenesis. By integrating gene expression analysis, immunofluorescence, genetic and adeno-associated virus expressing TAU mouse models, we found a TAU-dependent increase in CB2 receptor expression in hippocampal neurons, that occurs as an early event in the pathology and was maintained until late stages. These changes were accompanied by alterations in the endocannabinoid metabolism. Remarkably, CB2 ablation in mice protects from neurodegeneration induced by hTAU P301L overexpression, corroborated at the level of cognitive behaviour, synaptic plasticity, and aggregates of insoluble TAU. At the level of neuroinflammation, the absence of CB2 did not produce significant changes in concordance with a possible neuronal location rather than its classic glial expression in these models. These findings were corroborated in post-mortem samples of patients with Alzheimer’s disease, the most common tauopathy. Our results show that neurons with accumulated TAU induce the expression of the CB2 receptor, which enhances neurodegeneration. These results are important for our understanding of disease mechanisms, providing a novel therapeutic strategy to be investigated in tauopathiespost-print8580 K

Hydrogels Based on Chitosan and Chitosan Derivatives for Biomedical Applications

Chitosan (CS) is a polymer obtained from chitin, being this, after the cellulose, the most abundant polysaccharide. The fact of (i) CS being obtained from renewable sources; (ii) CS to possess capability for doing interactions with different moieties being such capability dependent of pH; (iii) plenty of possibilities for chemical modification of CS; and (iv) tuning the final properties of CS derivatives makes this polymer very interesting in academic and technological points of view. In this way, hydrogels based on CS and on CS derivatives have been widely used for biomedical applications. Other important technological applications can be also cited, such as adsorbent of metals and dyes in wastewater from industrial effluents. In pharmaceutical field, hydrogels based on CS are often used as drugs’ and proteins’ carrier formulations due to the inherent characteristics such as the biocompatibility, nontoxicity, hydrophilicity, etc. This chapter is an attempt for updating and joining the plenty of available information regarding the preparation, characterization, and biomedical application of hydrogels based on chitosan and chitosan derivatives. More than 260 references are provided, being the majority of them published in the last 10 years

Chitosan/TPP microparticles obtained by microemulsion method applied in controlled release of heparin

AbstractThis work deals with the preparation of chitosan/tripolyphosphate microparticles (CHT/TPP) using microemulsion system based on water/benzyl alcohol. The morphology of the microparticles was evaluated by scanning electron microscopy (SEM). The microparticles were also characterized through infrared spectroscopy (FTIR) and wide-angle X-ray scattering (WAXS). The morphology and crystallinity of microparticles depended mainly on CHT/TPP ratio. Studies of controlled release of HP were evaluated in distilled water and in simulated gastric fluid. Besides, the profile of HP releasing could be tailored by tuning the CHT/TPP molar ratio. Finally, these prospective results allow the particles to be employed as site-specific HP controlled release system