Dissolution enhancement of active pharmaceutical ingredients by therapeutic deep eutectic systems

A therapeutic deep eutectic system (THEDES) is here defined as a deep eutectic solvent (DES) having an active pharmaceutical ingredient (API) as one of the components. In this work, THEDESs are proposed as enhanced transporters and delivery vehicles for bioactive molecules. THEDESs based on choline chloride (ChCl) or menthol conjugated with three different APIs, namely acetylsalicylic acid (AA), benzoic acid (BA) and phenylacetic acid (PA), were synthesized and characterized for thermal behaviour, structural features, dissolution rate and antibacterial activity. Differential scanning calorimetry and polarized optical microscopy showed that ChCl:PA (1:1), ChCl:AA (1:1), menthol:AA (3:1), menthol:BA (3:1), menthol:PA (2:1) and menthol:PA (3:1) were liquid at room temperature. Dissolution studies in PBS led to increased dissolution rates for the APIs when in the form of THEDES, compared to the API alone. The increase in dissolution rate was particularly noticeable for menthol-based THEDES. Antibacterial activity was assessed using both Gram-positive and Gram-negative model organisms. The results show that all the THEDESs retain the antibacterial activity of the API. Overall, our results highlight the great potential of THEDES as dissolution enhancers in the development of novel and more effective drug delivery systems.

Cost efficiency and resistance to chemical attack of a fly ash geopolymeric mortar versus epoxy resin and acrylic paint coatings

This article presents results of an experimental investigation on the resistance to chemical attack (with sulphuric, hydrochloric and nitric acid) of several materials: OPC concrete, high-performance concrete, epoxy resin, acrylic painting and a fly ash-based geopolymeric mortar). Three types of acids with three high concentrations (10, 20 and 30%) were used to simulate long-term degradation. A cost analysis was also performed. The results show that the epoxy resin has the best resistance to chemical attack independently of the acid type and the acid concentration. However, the cost analysis shows that the epoxy resin-based solution is the least cost-efficient solution being 70% above the cost efficiency of the fly ash-based geopolymeric mortar.

Development of procedures for the design, optimization and manufacturing of customized orthopaedic and trauma implants: Geometrical/anatomical modelling from 3D medical imaging

Tese de Doutoramento (Programa Doutoral em Engenharia Biomédica)

Nanotechnological approaches using curcumin and Withania somnifera: neuroprotection and antimicrobial activities

Tese de Doutoramento em Biologia de Plantas

Development of folate-targeted liposomes for rheumatoid arthritis therapy

Tese de Doutoramento em Biologia Molecular e Ambiental (área de especialização em Biologia Celular e Saúde).

Protein-based nanodevices for therapeutic applications

Tese de Doutoramento em Biologia Molecular e Ambiental (área de especialização em Biologia Celular e Saúde).

Biosurfactants produced by marine microorganisms with therapeutic applications

Marine microorganisms possess unique metabolic and physiological features and are an important source of new biomolecules, such as biosurfactants. Some of these surface-active compounds synthesized by marine microorganisms exhibit antimicrobial, anti-adhesive and anti-biofilm activity against a broad spectrum of human pathogens (including multi-drug resistant pathogens), and could be used instead of the existing drugs to treat infections caused by them. In other cases, these biosurfactants show anti-cancer activity, which could be envisaged as an alternative to conventional therapies. However, marine biosurfactants have not been widely explored, mainly due to the difficulties associated with the isolation and growth of their producing microorganisms. Culture-independent techniques (metagenomics) constitute a promising approach to study the genetic resources of otherwise inaccessible marine microorganisms without the requirement of culturing them, and can contribute to discover novel biosurfactants with significant biological activities. This paper reviews the most relevant biosurfactants produced by marine microorganisms with potential therapeutic applications and discusses future perspectives and opportunities to discover novel molecules from marine environments.

A possible contribution to improving the therapeutic potentials of Babor's Typology of Alcohol Dependent Patients

ABSTRACT Objective The objective of this study was to replicate Babor's Typology and to explore clinical features related to personality traits that may underlie this classification, in order to improve its therapeutic possibilities. Methods Observational prospective study on a group of 273 male alcoholics. After a replication of Babor's variables, Cluster Analysis, Chi-Square – applied on clinical variables related to a Lappda Tipology – and Kappa tests were performed. Results The study identified two distinct clusters that held similar features to those described for the Type A/Type B classification. Besides presenting a lower socio-economic situation, Cluster 2 patients were associated with higher vulnerability and severe clinical features and also differed from Cluster 1 in their response to treatment. These replicated clusters retained connections and also differences in relation to the variables derived from the Lappda Typology. Conclusion Considering that each of the two replicated clusters seem to be associated to different personality traits – according to their correlations to the affective, cognitive and behavioral dimensions brought forward by the Lappda Typology – it is acceptable that this study may contribute to the development of more comprehensive and effective therapeutic strategies specifically tailored to target more specific personality traits of these subgroups of alcoholic patients.

Fundamental studies on natural deep eutectic solvents: physico-chemical, thermal and rheological properties

When combined at particular molar fractions, sugars, aminoacids or organic acids a present a high melting point depression, becoming liquids at room temperature. These are called Natural Deep Eutectic Solvents – NADES and are envisaged to play a major role on the chemical engineering processes of the future. Nonetheless, there is a significant lack of knowledge of its fundamental and basic properties, which is hindering their industrial applications. For this reason it is important to extend the knowledge on these systems, boosting their application development [1]. In this work, we have developed and characterized NADES based on choline chloride, organic acids, amino acids and sugars. Their density, thermal behavior, conductivity and polarity were assessed for different compositions. The conductivity was measured from 0 to 40 °C and the temperature effect was well described by the Vogel-Fulcher-Tammann equation. The morphological characterization of the crystallizable materials was done by polarized optical microscopy that provided also evidence of homogeneity/phase separation. Additionally, the rheological and thermodynamic properties of the NADES and the effect of water content were also studied. The results show these systems have Newtonian behavior and present significant viscosity decrease with temperature and water content, due to increase on the molecular mobility. The anhydrous systems present viscosities that range from higher than 1000Pa.s at 20°C to less than 1Pa.s at 70°C. DSC characterization confirms that for water content as high as 1:1:1 molar ratio, the mixture retains its single phase behavior. The results obtained demonstrate that the NADES properties can be finely tunned by careful selection of its constituents. NADES present the necessary properties for use as extraction solvents. They can be prepared from inexpensive raw materials and tailored for the selective extraction of target molecules. The data produced in this work is hereafter importance for the selection of the most promising candidates avoiding a time consuming and expensive trial and error phase providing also data for the development of models able to predict their properties and the mechanisms that allow the formation of the deep eutectic mixtures.

Development of Monoolein-based lipofection vectors for therapeutic siRNA delivery

Tese de Doutoramento em Biologia Molecular e Ambiental - Especialidade em Biologia Celular e Saúde

Pharmacological evaluation of plant extracts from Chapada Diamantina (Bahia, Brazil): Focus on antioxidant and cytotoxic properties

Tese de Doutoramento em Biologia de Plantas MAP - Bioplant

Therapeutic approach to patients complaining of high blood pressure in a cardiological emergency room

OBJECTIVE: To evaluate the management of patients complaining of high blood pressure (BP) in a cardiological emergency room. METHODS: Patients referred to the cardiological emergency room with the main complaint of high blood pressure were consecutively selected. The prescriptions and the choice of antihypertensive drugs were assessed. The classification of these patients as hypertensive emergencies or pseudoemergencies, according to the physician who provided initial care, was recorded. RESULTS: From a total of 858 patients presenting to the emergency room, 80 (9.3%) complained of high BP, and 61 (76.3%) received antihypertensive drugs. Sublingual nifedipine was the most commonly used drug (59%). One patient received intravenous medication, one patient was hospitalized and 6 patients (7.5%) were classified as hypertensive emergencies or pseudoemergencies. CONCLUSION: High BP could seldom be classified as a hypertensive emergency or pseudoemergency, even though it was a frequent complaint (9.3% of visits). Currently, the therapeutic approach is not recommended, even in specialized clinics.

Aortic valve assessment. Anatomical study of 100 healthy human hearts

PURPOSE: To assess anatomical characteristics of the aortic valve, so that they may be useful in diagnostic situations and surgical treatment. METHODS: The study analyzed 100 healthy fixed human hearts; 84% of them obtained from males, 61% of them from Caucasian individuals. The ages of the individuals ranged from 9 to 86 years (mean 30±15.5 years). The characteristics assessed related to age, sex, and race were the following: number and height of the cusps, size of the lunulae, internal and external intercommissural distance, position of the coronary ostium in relation to the aortic valve, position of the ventricular septum in relation to the aortic valve, thickness of the cusps. RESULTS: All hearts assessed had a tricuspidal aortic valve. In regard to the height of the cusps and size of the lunula, the left coronary cusp was larger, followed by the right coronary cusp and the noncoronary cusp. The internal and external intercommissural distances had mean values of 24.6±5.7mm and 19.7±7mm, respectively. In regard to the position of the coronary ostia, in one heart two ostia emerged from the left coronary sinus, and in another, the ostium was supracommissural. The mean diameter of the aorta was 21.8±3.6mm, and there were no significant sexual or racial differences, but the diameter increased progressively with the increase in age. The thickness of the cusps did not show any significant difference in the 3 points assessed. CONCLUSION: The aortic valve annulus did not show a perfect circumference, with some variations in the measurements of the annulus, in the cusps and in the relation with the ventricular septum.

Chemical functionalization in bionanoparticles

Dissertação de mestrado em Biofísica e Bionanossistemas

Response of blood pressure to maximum exercise in hypertensive patients under different therapeutic programs

OBJECTIVE: To evaluate the behavior of blood pressure during exercise in patients with hypertension controlled by frontline antihypertension drugs. METHODS: From 979ergometric tests we retrospectively selected 49 hipertensive patients (19 males). The age was 53±12 years old and normal range rest arterial pressure (<=140/90 mmHg) all on pharmacological monotherapy. There were 12 on beta blockers; 14 on calcium antagonists, 13 on diuretics and 10 on angiotensin converting enzyme inhibitor. Abnormal exercise behhavior of blood pressure was diagnosed if anyone of the following criteria was detected: peak systolic pressure above 220 mmHg, raising of systolic pressure > or = 10 mmHg/MET; or increase of diastolic pressure greater than 15 mmHg. RESULTS: Physiologic response of arterial blood pressure occurred in 50% of patients on beta blockers, the best one (p<0.05), in 36% and 31% on calcium antagonists and on diuretics, respectively, and in 20% on angiotensin converting enzyme inhibitor, the later the leastr one (p<0.05). CONCLUSION: Beta-blockers were more effective than calcium antagonists, diuretics and angiotensin-converting enzyme inhibitors in controlling blood pressure during exercise, and angiotensin converting enzyme inhibitors the least effective drugs.