Ana Cristina Santos

Lymphatic Uptake of Pulmonary Delivered Radiolabelled Solid Lipid Nanoparticles

Lymphatic drainage plays an important role in the uptake of particulates in the respiratory system, being also associated to the spreading of lung cancer through metastasis development. In recent years solid lipid nanoparticles (SLN) have been proposed as carriers of anti-tumoural drugs, for their low toxicity and surface characteristics make them suitable for either imaging (gamma-scintigraphy) or therapy upon encapsulation of cytotoxic drugs. Assessment of inhaled radiolabelled SLN biodistribution is described in the present work. Methods : Nanoparticles (200 nm) were radiolabelled with 99m Tc using the lipophilic chelator d, l -hexamehylpropyleneamine oxime (HMPAO). Biodistribution studies were carried out following aerosolisation and administration of a 99m Tc-HMPAO-SLN suspension to a group of adult male Wistar rats. A 60 min dynamic image acquisition was performed in a gamma-camera, followed by static image collection at 30 min intervals up to 4 h postinhalation. Radiation counting was performed in organ samples, collected after the animals were sacrificed. Results : The data show an important and significant uptake of the radiolabelled SLN into the lymphatics after inhalation, and a high rate of distribution in periaortic, axillar and inguinal lymph nodes. Conclusion Results indicate that SLN could be effective colloidal carriers for lymphoscintigraphy or therapy upon pulmonary delivery.

Poly(dimethyl siloxane) surface modification by low pressure plasma to improve its characteristics towards biomedical applications

Poly(dimethyl siloxane) elastomer, (PDMS) is widely used as a biomaterial. However, PDMS is very hydrophobic and easily colonized by several bacteria and yeasts. Consequently, surface modification has been used to improve its wettability and reduce bacterial adhesion. The aim of this work was to modify the PDMS surface in order to improve its hydrophilicity and bacterial cell repulsion to be used as a biomaterial. Plasma was used to activate the PDMS surface and sequentially promote the attachment of a synthetic surfactant, Pluronic F-68, or a polymer, Poly(ethylene glycol) methyl methacrylate, PEGMA. Bare PDMS, PDMS argon plasma activated, PDMS coated with Pluronic F-68 and PEGMA-grafted PDMS were characterized by contact angle measurements, X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). The influence of the surface modifications on blood compatibility of the materials was evaluated by thrombosis and haemolysis assays. The cytotoxicity of these materials was tested for mouse macrophages. After modification, AFM results suggest the presence of a distinct layer at the surface and by the contact angle measures it was observed an increase of hydrophilicity. XPS analysis indicates an increase of the oxygen content at the surface as a result of the modification. All the studied materials revealed no toxicity and were found to be non-haemolytic or in some cases slightly haemolytic. Therefore, plasma was found to be an effective technique for the PDMS surface modification.

A gallium complex with a new tripodal tris-hydroxypyridinone for potential nuclear diagnostic imaging: solution and in vivo studies of 67Ga-labeled species

The gallium(III) complex of a new tripodal 3-hydroxy-4-pyridinone (3,4-HP) chelator has been studied in terms of its physico-chemical and in vivo properties aimed at potential application as probe for nuclear imaging. In particular, based on spectrophotometric titrations, the hexa-coordinated (1:1) gallium complex appeared as the major species in a wide physiological acid-neutral pH range and its high stability (pGa=27.5) should avoid drug-induced toxicity resulting from Ga(III) accumulation in tissues due to processes of transmetallation with endogenenous ligands or demetallation. A multinuclear ((1)H and (71)Ga) NMR study gave some insights into the structure and dynamics of the gallium(III) chelate in solution, which are consistent with the tris-(3,4-HP) coordination and an eventual pseudo-octahedral geometry. Biodistribution and scintigraphic studies of the (67)Ga(III) labelled chelate, performed in Wistar rats, confirmed the in vivo stability of the radiolabelled complex, its non interaction with blood proteins and its quick renal clearance. These results indicate good perspectives for potential application of extrafunctionalized analogues in radiodiagnostic techniques.

Design and characterization of bi-soft segmented polyurethane microparticles for biomedical application.

Bi-soft segmented poly(ester urethane urea) microparticles were prepared and characterized aiming a biomedical application. Two different formulations were developed, using poly(propylene glycol), tolylene 2,4-diisocyanate terminated pre-polymer (TDI) and poly(propylene oxide)-based tri-isocyanated terminated pre-polymer (TI). A second soft segment was included due to poly(ɛ-caprolactone) diol (PCL). Infrared spectroscopy, used to study the polymeric structure, namely its H-bonding properties, revealed a slightly higher degree of phase separation in TDI-microparticles. TI-microparticles presented slower rate of hydrolytic degradation, and, accordingly, fairly low toxic effect against macrophages. These new formulations are good candidates as non-biodegradable biomedical systems.

The motives for cooperation in work organizations

This paper aims to contribute to a better understanding of cooperation in productive ventures, conceived of as collective action endeavours that require cooperation rather than mere coordination. It is argued that cooperative behaviour is grounded on three kinds of ‘common goods’, defined as goods that are shared and recognized as beneficial by the workers. These comprise common goals, relational satisfaction, and moral norms and values. The commonly held goods are associated with motives and behavioural rules which constitute both the reasons for cooperating and the means through which the dilemmatic nature of cooperation is overcome. It is further argued that the binding character of these rules is closely linked to humans’ ability and opportunity to communicate. Normative guidelines relative to management practices and directions for future research are also derived.

The effect of the amide substituent on the biodistribution and tolerance of lanthanide(iii) dota-tetraamide derivatives

Objectives:Recent advances in the design of MRI contrast agents have rendered the lanthanide complexes of DOTA-tetraamide ligands of considerable interest, both as responsive MR agents and paramagnetic chemical exchange saturation transfer agents. The potential utility of these complexes for in vivo applications is contingent upon them being well tolerated by the body. The purpose of this study was to examine how the nature of the amide substituent, and in particular its charge, affected the fate of these chelates postinjection. Materials and Methods:Complexes of 6 DOTA-tetraamide ligands were prepared in which the nature of the amide substituent was systematically altered. The 6 ligands formed 3 series: a phosphonate series that included tri-cationic, mono-anionic, and poly-anionic complexes; a carboxylate series made up of a tri-cationic complex and a mono-anionic complex; and lastly, a tri-cationic complex with an aromatic amide substituent. These complexes were labeled with an appropriate radioisotope, either 153Gd or 177Lu, and the biodistribution profiles in rats recorded 2 hours postinjection. Results:Biodistribution profiles were initially acquired at low doses to minimize adverse effects. All the complexes studied were found to be excreted primarily through the renal system, with the majority of the dose being found in the urine. None of the complexes exhibited substantial uptake by bone, liver, and spleen, except for a complex with 4 phosphonate groups that exhibited significant bone targeting capabilities. Increasing the dose of each complex to that of a typical MR contrast agent was found to render all 3 tri-cationic complexes studied here acutely toxic. In contrast, no ill effects were observed after administration of similar doses of the corresponding anionic complexes. Conclusions:The absence of uptake by the liver and spleen indicate that irrespective of the ligand structure and charge, these complexes are not prone to dissociation in vivo. This is in agreement with previously published work that indicates high kinetic inertness for this class of compounds. At low doses, all complexes were well tolerated; however, for applications that require higher doses, the structure and charge of the ligand becomes a fundamentally important parameter. The results reported herein demonstrate the importance of incorporating negatively charged groups on amide substituents if a DOTA-tetraamide complex is to be employed at high doses in vivo.

Sonication-Assisted Layer-by-Layer Assembly for Low Solubility Drug Nanoformulation

Sonication-assisted layer-by-layer (LbL) self-assembly is a nanoencapsulation technique based on the alternate adsorption of oppositely charged polyelectrolytes, enabling the encapsulation of low solubility drugs. In this work, a top-down LbL technique was performed using a washless approach and ibuprofen (IBF) as a model class II drug. For each saturated layer deposition, polyelectrolyte concentration was determined by titration curves. The first layer was constituted by cationic poly(allylamine hydrochloride) (PAH), given the IBF negative surface charge, followed by anionic polystyrenesulfonate (PSS). This polyelectrolyte sequence was made up with 2.5, 5.5, and 7.5 bilayer nanoshells. IBF nanoparticles (NPs) coated with 7.5 bilayers of PAH/PSS showed 127.5 ± 38.0 nm of particle size, a PDI of 0.24, and a high zeta potential (+32.7 ± 0.6 mV), allowing for a stable aqueous nanocolloid of the drug. IBF entrapment efficiency of 72.1 ± 5.8% was determined by HPLC quantification. In vitro MTT assay showed that LbL NPs were biocompatible. According to the number of coating layers, a controlled release of IBF from LbL NPs was achieved under simulated intestinal conditions (from 5 h up to 7 days). PAH/PSS-LbL NPs constitute a potential delivery system to improve biopharmaceutical parameters of water low solubility drugs.

Are we there yet? Queer sexual encounters, legal recognition and homonormativity

In 2010, Portugal became the eighth country worldwide to approve same-sex civil marriage. Such legal change is a recent addition to the achievements that have put Portugal at the forefront of sexual citizenship rights for lesbian, gay, bisexual, and transgender (LGBT) people in Europe. This article investigates the political path of LGBT rights in this Southern European, majority Catholic, and post-dictatorship country, exploring the role of the Portuguese LGBT movement in contributing to change. This research highlights how the state is willing to compensate – via legal recognition – queer sexual encounters to the extent that they willingly embrace the dominant values of respectability and normalcy. In this respect, the approval of same-sex marriage offers the opportunity to discuss issues of agency, citizenship, recognition, and normativity. The paper begins by contextualizing sexual citizenship in democratic Portugal, providing an analytical account of the LGBT movement. In the second section, I suggest that a ‘politics of containment’ has characterized much of recent public discussion about sexual and reproductive rights, and I provide some examples. In the last section, I discuss the political and cultural implications of same-sex marriage law, with a particular focus on issues of normalization and homonationalism – that is how the state can actively contribute to the creation of the acceptable ‘normal gay’ with the compliance of LGBT activism.

Sexual Orientation in Portugal: Towards Emancipation

This essay analyzes the emergence of the Portuguese lesbian-gay-bisexual-transsexual (LGBT) movement, identifying actors, alliances, impasses, and possibilities for sexual emancipation in a dominantly and proudly Catholic and heterosexual society. The Portuguese LGBT movement has achieved some power and visibility in the socio-political field since the 1990s. After a decade in which LGBT rights seemed condemned to oblivion on the part of Portuguese legislation, on 15 March 2001, Parliament made history when it passed a law on common-law partnerships for all citizens, independent of their sexual orientation. Finally, I address whether this form of oppression contains potential for emancipation in its broader sense.

Living Apart Relationships in Contemporary Europe: Accounts of Togetherness and Apartness

Drawing on a European cross-national biographical-narrative study of intimate life, this article discusses the complexity of experiences of ‘togetherness’ and ‘apartness’ amongst people in living apart relationships. We explore the five main ways in which interviewees spoke about and understood their current living apart relationships (as: chosen; temporary; transitional; undecided; and unrecognisable), which we argue shows the need for a broader conceptualisation of this form of intimate relationship than is suggested by the established notion of ‘living apart together’. The article points to interviewees’ varying experiences of receiving or being denied recognition and acceptance by others as belonging to a couple, as well as to their differing degrees of desire for, or rebellion against, expectations that living apart relationships should ‘progress’ towards cohabitation.