M. Elisabete C.D. Real Oliveira

University of Minho · Centro de Física (CFUM-UP)

Opportunistic fungi cause lethal systemic infections and impose high medical costs to health systems. The World Health Organization has recognized the importance of fungal infections, including them in its global priority list guiding research, development, and discovery of new therapeutic approaches. Fungal vaccine development has been proposed as...

Pancreatic cancer evades most of the current therapies and there is an urgent need for new treatments that could efficiently eliminate this aggressive tumor, such as the blocking of routes driving cell proliferation. In this work, we propose the use of small interfering RNA (siRNA) to inhibit the combined expression of FOSL-1 and YAP, two signaling...

Since its revolutionary discovery in 2004, graphene-a two-dimensional (2D) nanomaterial consisting of single-layer carbon atoms packed in a honeycomb lattice-was thoroughly discussed for a broad variety of applications including quantum physics, nanoelectronics, energy efficiency, and catalysis. Graphene and graphene-based nanomaterials (GBNs) have...

Non-viral gene therapy based on gene silencing with small interfering RNA (siRNA) has attracted great interest over recent years. Among various types of cationic complexation agents, amino acid-based surfactants have been recently explored for nucleic acid delivery due to their low toxicity and high biocompatibility. Monoolein (MO), in turn, has be...

Purpose: AntiOxCIN3 is a novel mitochondriotropic antioxidant developed to minimize the effects of oxidative stress on neurodegenerative diseases. Prior to an investment in pre-clinical in vivo studies, it is important to apply in silico and biophysical cell-free in vitro studies to predict AntiOxCIN3 biodistribution profile, respecting the need t...

This chapter presents an overview of the different types of Organic Nanocarriers (ONCs) for brain delivery, including a description of their advantages and disadvantages, and a set of preclinical studies illustrating the most effective strategies for effective brain distribution. The main difficulties in the treatment of these diseases are associat...

HIV/AIDS stands as a global burden, and vaginal microbicides constitute a promising strategy for topical pre-exposure prophylaxis. Preceding the development of a microbicide containing tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC), in silico and in vitro studies were performed to evaluate the physicochemical characteristics of both dr...

In the present work, lipid nanosystems containing omega-3 fatty acid (nanostructured lipid carriers, NLCs) or omega-3 fatty acid and resveratrol (liposomes) were developed to improve cotton textile substrates as dressings with anti-inflammatory properties for wound healing applications. Lipid nanosystems were incorporated into woven, non-woven and...

Different positive pharmacological effects have been attributed to the natural product resveratrol (RSV), including antioxidant, anti-aging and cancer chemopreventive properties. However, its low bioavailability and rapid metabolic degradation has led to the suspicion that many of the biological activities of this compound observed in vitro may not...

Many graphene-based materials (GBNs) applied to therapy and diagnostics (theranostics) in cancer have been developed. Most of them are hybrid combinations of graphene with other components (e.g, drugs or other bioactives, polymers, and nanoparticles) aiming toward a synergic theranostic effect. However, the role of graphene in each of these hybrids...

Abstract: The possibility of using the RNA interference (RNAi) mechanisms in gene therapy was one of the scientific breakthroughs of the last century. Despite the extraordinary therapeutic potential of this approach, the need for an efficient gene carrier is hampering the translation of the RNAi technology to the clinical setting. Although a divers...

Diclofenac (DCF), the most widely consumed non-steroidal anti-inflammatory drug (NSAID) worldwide, is associated with adverse typical effects, including gastrointestinal (GI) complications. The present study aims to better understand the topical toxicity induced by DCF using membrane models that mimic the physiological, biophysical, and chemical en...

The possibility of using the RNA interference (RNAi) mechanisms in gene therapy was one of the scientific breakthroughs of the last century. Despite the extraordinary therapeutic potential of this approach, the need for an efficient gene carrier is hampering the translation of the RNAi technology to the clinical setting. Although a diversity of nan...

In this work, the binding constant of ACV to human serum albumin was determined by binding isotherms. Nonlinear least-squares best fit to intrinsic fluorescence quenching effect of the drug was used to determine the association constants between drug and the serum protein at one affinity binding site (Kb=1.79x10 3 M-1). A red shift of the fluoresce...

Age related neurodegenerative disorders (ARND) are presented as the most debilitating and challenging diseases associated with the central nervous system. Despite the advent of active molecules with a positive role on neurodegenerative mechanisms, many of the current therapeutic strategies remain ineffective in treating or preventing ARND. Lipid na...

Herpes infections are very frequent, affecting both men and women, especially those whose immune system is weakened, and causing manifestations in face, lips, oral, nasal and genital mucosa. Herpes can also spread to other parts of the body such as the central nervous system and leave severe squeals in about 80% of cases. The current topical therap...

Cancer remains a global health problem and according to the International Agency for Research on Cancer, the incidence of all cancer cases will raise from 12.7 million new cases in 2008 to 21.2 million by 2030. [1] Doxorubicin (DOX) is a wide-spectrum “first-line” anticancer drug. However, its clinical application is limited as it is often associat...

N anotechnology promises to be a wave turner in various medical and pharmaceutical fields such as drug delivery, diagnostics and in the pharmacokinetic profiling of drugs. In order to obtain an efficient therapeutic effect, lipid nanosystems have demonstrated to be promising drug delivery systems since their lipophilic and hydrophilic components al...

Curcumin, the golden powder with weak bioavailability, also known for its anti-inflammatory and antioxidant properties, has been a target of great heed in various medical fields, namely in the treatment of neurodegenerative diseases [1]. In this particular field, multiple pharmacological targets, capable of promoting a decrease in peptidic aggregat...

N anotechnology promises to be a wave turner in various medical and pharmaceutical fields such as drug delivery, diagnostics and in the pharmacokinetic profiling of drugs. In order to obtain an efficient therapeutic effect, lipid nanosystems have demonstrated to be promising drug delivery systems since their lipophilic and hydrophilic components al...

The development of suitable carriers to enhance the bioavailability and therapeutic effect of drugs has been the focus of intense research in the recent years. Liposomes were among the first lipid nanoparticles to make a successful passage from concept to clinical application. The design of liposomes can be improved by tuning membrane properties an...

Liposomes have received extensive attention as nanocarriers for bioactive compounds due to their good biocompatibility, possibility of targeting and incorporation of hydrophilic and hydrophobic compounds. Although generally considered as safe, detailed knowledge of the effects induced in cells and tissues with which they interact is still underexpl...

There is a direct correlation between physicochemical properties of nanocarrier systems and their biological performance, including stability in physiological conditions, cellular internalization and transfection efficiency. Therefore, understanding the biophysical aspects that affect self-assembled nanocarriers is determinant for a rational design...

Statement of significance: This work describes the immunomodulation capacity of the previously validated antigen delivery system (ADS) composed by dioctadecyldimethylammonium bromide (DODAB) and monoolein (MO) lipids incorporating the cell wall surface proteins (CWSP) from C. albicans. Here, we not only present the ability of this system in facili...

Liposomes have received extensive attention as nanocarriers for bioactive compounds due to their good biocompatibility, possibility of targeting and incorporation of hydrophilic and hydrophobic compounds. Although generally considered as safe, detailed knowledge of the effects induced in cells and tissues with which they interact is still underexpl...

We report the development and characterization of a novel nanometric system for specific delivery of therapeutic siRNA for cancer treatment. This vector is based on a binary mixture of the cationic surfactant dioctadecyldimethylammonium chloride (DODAC) and the helper lipid monoolein (MO). These liposomes were previously validated by our research g...

While the delivery of small interfering RNAs (siRNAs) is an attractive strategy to treat several clinical conditions, siRNA-nanocarriers’ stability after intravenous administration is still a major obstacle for the development of RNA-interference based therapies. But, although the need for stability is well recognized, the notion that strong stabil...

Encapsulation of nonsteroidal or non-steroidal anti-inflammatory drugs (NSAID) in nanocarrier systems aims to enhance bioavailability and to decrease toxicity of these drugs and thus improve the efficacy of treatments. With this aim two types of nanoparticles were prepared and compared: lipid nanoparticles, made of cetyl palmitate and Miglyol 812 w...

The aim of this work was to study the central and peripheral thickness of several contact lenses (CL) with different powers and analyze how thickness variation affects CL oxygen transmissibility. Four daily disposable and five monthly or biweekly CL were studied. The powers of each CL were: the maximum negative power of each brand; -6.00D; -3.00D;...

We describe the preparation and characterization of DODAB:MO-based liposomes and demonstrate their adjuvant potential and use in antigen delivery. Liposomes loaded with Candida albicans proteins assembled as stable negatively charged spherical nanoparticles with a mean size of 280nm. High adsorption efficiency (91.0±9.0%) is attained with high lipi...

Dioctadecyldimethylammonium bromide (DODAB):Monoolein (MO) lipoplexes have mainly been studied within the range of high molar ratios of DODAB, with noticeable transfection efficiencies in the Human Embryonic Kidney (HEK, a.k.a. 293 T) cell line. In this work, we intend to study the effect of high MO content on the structure and physicochemical prop...

Dioctadecyldimethylammonium bromide (DODAB):1-monooleoyl-rac-glycerol (MO) cationic liposomes were reported as a promising alternative to common transfection agents, showing superior effectiveness on the transfection of the 293 T mammalian cell line with pSV-β-gal plasmid DNA. The study of DODAB:MO aggregates in the absence of DNA has indicated tha...

The development of cationic liposomes for gene delivery has been a focus of intense research in recent years. The combination of different cationic lipids is one of the strategies to improve the efficiency of liposomal nanocarriers for gene therapy. In this study we included a third lipid component (β-[N-(N’,N’-dimethylaminoethane)-carbamoyl] chole...

The consequences for the transfection efficiencies of different lipoplexes preparation methods, largely remain to be explored, but the knowledge of how different experimental approaches can affect the physicochemical properties and transfection efficiency is essential for a proper tailoring of transfection complexes to particular applications. Ther...

The aim of this study was to analyze the influence of different lens care systems in surface roughness and refractive index (RI) of contact lenses (CL). This information provides us with a better understanding of how care solutions affect CL materials. Several CL and three commercially available and appropriate lens care solutions were used (two po...

This study describes a novel liposomal formulation for siRNA delivery, based on the mixture of the neutral lipid monoolein (MO) and cationic lipids of the dioctadecyldimethylammonium (DODA) family. The cationic lipids dioctadecyldimethylammonium bromide (DODAB) and chloride (DODAC) were compared in order to identify which one will most efficiently...

To measure different parameters of lower tear meniscus height (TMH) by using photography with open software of measurement. TMH was addressed from lower eyelid to the top of the meniscus (absolute TMH) and to the brightest meniscus reflex (reflex TMH). 121 young healthy subjects were included in the study. The lower tear meniscus was videotaped by...

The aim of this work was to measure the central thickness of several contact lenses (CL) with different powers and to analyze how thickness variation affects the CL oxygen transmissibility.

Dioctadecyldimethylammonium Bromide or Chloride (DODAX, X representing Br- or Cl- counter ions):1-monooleoyl-rac-glycerol (MO) liposomes have recently been described as new promising alternative to common transfection reagents, due to the pioneering application of Monoolein (MO)as helper lipid in lipoplex structures [1, 2]. This work was focused on...

Purpose: The main goal was to study the biochemical composition of the tear film in two different times of the day. Methods: Tear samples were collected from 10 individuals, non contact lenses wearers, from the university population without pathologies. To assess daily variations in the tear film, samples were collected twice in the day, one ear...

Given these limitations, the intracellular delivery of genetic material can only be achieved through the use of physical, biological or chemical methods that promote gene insertion into cells. Physical methods have generally low in vivo applicability and include direct injection of NA into organs of live animals, micro projectile biolistics with a...

*

DNA/Cationic liposome complexes (lipoplexes) have been widely used as non-viral vectors for transfection. Neutral lipids in liposomal formulation are determinant for transfection efficiency using these vectors. In this work, we studied the potential of monoolein (MO) as helper lipid for cellular transfection. Lipoplexes composed of pDNA and dioctad...

The aim of the present study was to analyse the quality and quantity of the tear film in a young, healthy and non-contact lens-wearing population with measurements taken in the morning and in the afternoon to establish if changes exist in these parameters. In a controlled laboratory setting, morning and afternoon clinical parameters of tear film we...

The main objective of this work was to increase the retarding effect of the acid dye Telon(®) Blue RR (C.I. Acid Blue 62; DyStar, Frankfurt, Germany) release on polyamide fibres dyeing by encapsulation of the dye in liposomes as an alternative to synthetic auxiliaries, in order to reduce effluent pollution. The retarding effect achieved with the us...

Purpose: White light optical profiling (WLOP), no usually applied to contact lenses (CL), is a well-established technique for non-contact measurement of surface topography over large areas at moderate lateral and high vertical resolution (sub-nanometer). The aim of this study is to analyze surface properties of five hydrogel CL evaluating represent...

To assess the disinfection efficacy of multipurpose solutions (MPS) against different bacterial species adhered either to silicon hydrogel or to conventional hydrogel contact lenses (CLs). The influences of the MPS formulation and the chemical composition of the lens material were investigated. This investigation followed the standard 14729, which...

There is an increasing interest in the textile industry for eco-friendly textile processing, in which the use of naturally occurring materials such as phospholipids becomes important. The non-uniformity that occurs in the dyeing process of polyamide, caused by the irregularities in the surface properties of the fiber, is reduced by the use of level...

Lipoplexes composed of pDNA and DODAB/MO at different molar ratios (4:1, 2:1 and 1:1) and different cationic lipid/DNA charge ratios were investigated. The physicochemical properties of the lipoplexes (size and charge), the pDNA complexation, and the effect of heparin on pDNA release, were studied by dynamic light scattering, zeta potential, and et...

This study was designed to qualitatively and quantitatively characterize the surface morphology of four unworn conventional hydrogel contact lenses (omafilcon, hioxifilcon, nelfilcon A, and ocufilcon B) and two silicone-hydrogel contact lenses (senofilcon A and comfilcon A) without surface treatment. Surface roughness was assessed using atomic forc...

The aim of this study was to characterize, qualitatively and quantitatively, the surface morphology of four unworn conventional hydrogel contact lenses (Omafilcon, Hioxifilcon-based, Nefilcon A and Ocufilcon B) by White Light Optical Profiling (WLOP). WLOP is an ideal technique for sampling larger areas as well as for higher measurement speed compa...

This study was designed to assess whether hydrogel contact lens (CL) surface hydrophobicity and roughness affect Staphylococcus epidermidis adhesion. Bacterial adhesion experiments were performed on two unworn silicone hydrogel and three unworn conventional hydrogel CLs using the S.epidermidis strain CECT 4184. Microbial colonization was assessed b...

The present invention relates to the application of monoolein-based cationic lipid systems for the complexation, transport and transfection of genetic material into target cells. The lipid systems are prepared through the conjugation of the neutral lipid monooleoyl-rac glycerol (Monoolein) with the cationic tensioactives derived from Dioctadecyldim...

In the millimolar concentration domain (typically 1mM), dioctadecyldimethylammonium bromide and chloride (DODAX, X representing Br− or Cl− counterions) molecules assemble in water as large unilamellar vesicles. Differential-scanning calorimetry (DSC) is a suitable technique to obtain the melting temperature (T m) characteristic of surfactant bilaye...