Alberto A. C. C. Pais

Comparison of dissolution profiles of Ibuprofen pellets.

In this work we use both model dependent and independent techniques to assess the difference between dissolution profiles in which ibuprofen, in the form of uncoated pellets, is used as a model drug. The choice of a proper regression function, the relevance of the estimated parameters and the influence of the choice of dissolution points in the assessment of differences is discussed. The results obtained via mean dissolution times (MDT) and fit-factors (f(1) and f(2)) are also discussed and a non-quantitative method based on profiles correlation with graphical representation (concentration vs. concentration and rate vs. rate) presented. The tested methods discriminate similarly between curves, although not in all cases, but those based on modeling, MDT and fit-factors have shown to be less informative than the correlation approach.

A realistic double many-body expansion (DMBE) potential energy surface for ground-state O3 from a multiproperty fit to ab initio calculations, and to experimental spectroscopic, inelastic scattering, and kinetic isotope thermal rate data

A new single-valued potential energy surface is reported for the ground electronic state of ozone from the double many-body expansion (DMBE) method. The parameters appearing in the DMBE formalism are determined from a multiproperty analysis using ab initio energies, and experimental data from spectroscopic, incomplete total scattering cross section, and kinetic thermal rate measurements. Based on this new surface, thermal rate coefficients for the 18O + 16O2 → 18O16O + 16O isotope exchange reaction are also reported over the temperature range 300 < T < 2000 K from the quasi-classical trajectory method.

Aggregation and gelation in hydroxypropylmethyl cellulose aqueous solutions

In this work we present an analysis of the thermal behavior of hydroxypropylmethyl cellulose aqueous solutions, from room temperature to higher temperatures, above gelation. We focus on significant aspects, essentially overlooked in previous work, such as the correlation between polymer hydrophobicity and rheological behavior, and the shear effect on thermal gelation. Micropolarity and aggregation of the polymer chains were monitored by both UV/vis and fluorescence spectroscopic techniques, along with polarized light microscopy. Gel formation upon heating was investigated using rheological experiments, with both large strain (rotational) tests at different shear rates and small strain (oscillatory) tests. The present observations allow us to compose a picture of the evolution of the system upon heating: firstly, polymer reptation increases due to thermal motion, which leads to a weaker network. Secondly, above 55 degrees C, the polymer chains become more hydrophobic and polymer clusters start to form. Finally, the number of physical crosslinks between polymer clusters and the respective lifetimes increase and a three-dimensional network is formed. This network is drastically affected if higher shear rates, at non-Newtonian regimes, are applied to the system.

The size of solid lipid nanoparticles: an interpretation from experimental design.

This study aimed to investigate the role of different factors affecting the size of solid lipid nanoparticles (SLN), prepared by the emulsification-solvent evaporation method. A double factorial design was conducted so as to cover a wide range of sizes, highlighting zones with different behaviour with respect to changes in the controlled variables: lipid concentration, solvent:lipid ratio and emulsifier concentration. The solvent:lipid ratio constituted the main factor influencing particle size. Increasing the amount of solvent induced a decrease in the size. This was a general trend, essentially independent from solvent and lipid type. The amount of emulsifier had a non-trivial impact on size, depending on whether systems were located below, above or close to the optimal surface coverage. The amount of lipid had a limited influence upon particle size, being more relevant for lower lipid concentrations. An optimal formulation was selected for intermediate levels of the three variables. Sonication reduced both particle size and polydispersity. These particles were also tested as drug carriers using simvastatin as a model of lipophilic drug. SLN were able to entrap a high amount of simvastatin, with little effect upon size and zeta potential, constituting a promising carrier for lipophilic drugs.

Skin cancer and new treatment perspectives: A review

Skin cancers are by far the most common malignancy of humans, particularly in the white population. The growing incidence of cutaneous malignancies has heralded the need for multiple treatment options. Although surgical modalities remain the mainstay of treatment, new research and fresh innovation are still required to reduce morbidity and mortality. Approaches for skin cancer may pass through new technological methods instead of new molecules. The first part of this paper provides a review of the state of the art regarding skin cancer disease as well as epidemiology data. Then, it describes the gold standards of the current recommended therapies worldwide and the actual needs of these patients. This is the first paper that highlights the novel and future therapeutic perspectives for the treatment of skin malignancies, new therapeutic agents and promising technological approaches, from nanotechnology to immunotherapy.

Interaction of Omeprazole with a Methylated Derivative of β-Cyclodextrin: Phase Solubility, NMR Spectroscopy and Molecular Simulation

PurposeCyclodextrins are known to be good solubility enhancers for several drugs, improving bioavailability when incorporated in pharmaceutical formulations. In this work we intend to assess and characterize the formation of inclusion complexes between omeprazole (OME) and a methylated derivative of β-cyclodextrin, methyl-β-cyclodextrin (MβCD). A comparison with results obtained from the most commonly used natural cyclodextrin, β-cyclodextrin (βCD) is also presented in most cases.Materials and MethodsThe interaction of OME with the mentioned cyclodextrins in aqueous solutions was studied by phase solubility studies, 1D 1H and 2D rotating frame nuclear overhauser effect NMR spectroscopy (ROESY) and Molecular Dynamics.ResultsThe solubility of OME was significantly increased by formation of inclusion complexes with each cyclodextrin. Phase solubility studies and continuous variation plots revealed that OME forms an inclusion complex in a stoichiometry of 1:1 with both cyclodextrins. 1H NMR and ROESY spectra of the inclusion complexes indicated that the benzimidazole moiety is included within the cyclodextrins cavities. Molecular dynamics showed that OME is more deeply included in the MβCD than in βCD cavity, in agreement with a larger apparent stability constant (KS) obtained for the inclusion complex with MβCD.ConclusionsMβCD proved to be an efficient enhancer of OME solubility, thus possessing characteristics for being an useful excipient in pharmaceutical formulations of this drug.

Modeling of DNA compaction by polycations

In this work we study polycations as efficient compacting agents of a medium size polyanion by means of Monte Carlo simulations. The systems are characterized in terms of a conformational analysis in which shape, overall dimensions, structure factors, radial distribution functions, and the degree of accumulation of the compaction agent near the polyanion are taken into consideration. Results show that the degree of compaction depends on the size of the positive chains and their number. The role of electrostatic interactions is paramount in the compaction process, and an increase in the number of molecules of the compacting agent or in the number of charges of each molecule leads to collapse, which may be followed by some unfolding in situations of overcharging. Compaction is associated with polycations promoting bridging between different sites in the polyanion. When the total charge of the polycations is significantly lower than that of the polyanion, interaction produces only a small degree of intrachain segregation in the latter, allowing for significant translational motion of the compacting agent along the longer chain. However, complete charge neutralization is not mandatory to achieve compact forms.

Co-encapsulating nanostructured lipid carriers for transdermal application: From experimental design to the molecular detail

Co-encapsulation of drugs directed at commonly associated diseases provides a convenient means for administration, especially if transdermally delivered. In this work, a comprehensive study for the co-encapsulation of drugs with a differential lipophilicity, olanzapine and simvastatin, and their transdermal delivery in a formulation containing nanostructured lipid carriers (NLC) is presented. Focus is given to the evaluation of a strategy in which NLC and chemical permeation enhancers are combined. It comprises in vitro, in silico and cellular viability approaches. The optimization and rationalization of the systems are carried out using a two-step factorial design. It is shown that the external medium in the NLC dispersion strongly influences permeation. It is also seen that the use of NLC determines a synergistic effect with selected permeation enhancers, thus promoting marked flux enhancement ratios (48 and 21, respectively for olanzapine and simvastatin) relative to the drugs in solution. The developed formulations can be considered non-irritant. A correlation between enhancer positioning in a lipid bilayer, partially governed by a H-bonding phenomenon, and enhancement effect is suggested from molecular dynamics studies and experimental observations.

Pseudomonas aeruginosa infection in cystic fibrosis lung disease and new perspectives of treatment: a review

Cystic fibrosis (CF) is a complex inherited disease which affects many organs, including the pancreas and liver, gastrointestinal tract and reproductive system, sweat glands and, particularly, the respiratory system. Pseudomonas aeruginosa is the main cause of chronic airway infection. In order to reduce morbidity and mortality due to lung infection by P. aeruginosa, aerosol antibiotics have been used to achieve high local concentrations in the airways and to reduce systemic toxicity. In the course of this review, the current treatments to control CF lung infections by P. aeruginosa are presented. Some innovative aerosol formulations such as liposomes and microspheres are herein reviewed, which may improve the efficiency of anti-pseudomonal agents, and ensure patients’ compliance to treatments, by reducing dosing frequency and/or drug dose, while maintaining therapeutic efficacy, preventing the occurrence of bacterial resistance and/or reducing adverse effects due to their controlled-release properties.

DNA–cationic amphiphile interactions

DNA shows strong interactions with cationic cosolutes and these have both biological and technological significance. We outline our research on various mixed systems of DNA and cationic amphiphiles including the interaction of DNA with simple cationic surfactants as well as the interaction with catanionic mixtures and positively charged catanionic vesicles. An overview from phase behavior to microstructure will be presented. We will also address DNA compaction and decompaction phenomena in different systems. Finally, simulations on DNA confinement and interaction with cationic polyions are considered.