Francisco Veiga has completed his PhD at the age of 30 years from Coimbra University. He is the dean of Faculty of Pharmacy in the University of Coimbra. He has published more than 200 papers in reputed journals.
Purpose: The aim of this work was to demonstrate the advantages of using polymeric mixed micelles (Pluronic® F68 and P123) to encapsulate meloxicam, when compared to meloxicam alone, and to characterize these micelles. Methods: Morphology was studied by transmission electron microscopy (TEM). 5 µl of freshly prepared micellar dispersions were placed on Formvar and allowed to dry for 5 min. To unveil the usefulness of such formulations concerning physical stability, formulations FM1-FM5 and meloxicam were dissolved in enteric and gastric medium. After 1 and 2 h we quantified meloxicam in gastric medium and after 3 and 4 h we quantified meloxicam in enteric medium. Quantification was performed using an UV spectrophotometer and absorbance taken at 363 nm. To determine encapsulation efficiency, FM1-FM5 were quantified immediately after preparation. Later on, micellar suspensions were centrifuged at 3000 g for 15 min using Amicon® Ultra 4 Centrifugal filter units, the supernatant was quantified and EE calculated based on the following equation: . Finally, cytotoxicity of formulations was assessed in Caco-2 cells by Alamar Blue assay, performing a screening of crescent concentrations (0.625%, 1.25%, 2.5%, 5% and 10 %) for each formulation. Results: Micelles were found to present very small sizes and approximately spherical shape, with meloxicam forming a circular line near to the micelle´s surface (Figure 2). All formulations significantly increased meloxicam physical stability in enteric medium (meloxicam: 3h 62.563%, 4h 35.890; FM1, FM2, FM3, FM4, FM5: 100%) In gastric medium, despite of FM2 and FM3 showed the best results (meloxicam: 1h 1.59%, 2h 1.54%; FM2: 1h 80.339%, 2h 66.281%; FM3: 1h 75.397%, 2h 61.260), all the other formulations showed a significant increase on stability. With the exception of FM1, all formulations demonstrate high EE % (FM1: 35.544±3.919, FM2: 93.162±1.071, FM3: 90.663±1.805, FM4: 89.840±1.991, FM5: 86.607±2.134). Finally, FM3 revealed no cytotoxicity in concentrations ranging from 0.625 to 5% and FM2 revealed no cytotoxicity in concentrations ranging from 0.625 to 2.5%. Conclusions: FM2 and FM3 seem to be promising formulations to efficiently encapsulate drugs with low water solubility, as meloxicam.
Glioblastoma multiforme (GBM) is an aggressive brain tumor with poor prognosis, mainly because standard treatment is not always effective enough in reaching tumor cells. Blood-brain barrier (BBB) is pointed out as one of great challenges in this field.  Considering the negative charge of BBB surface and its restricted permeability to small compounds, positively-charged nanoparticles have been developed to facilitate the transport of drugs through the BBB.  This work aimed at studying the interaction of different cationic surfactants used in lipid nanoparticle (LN) formulations with BBB, using atomistic simulations. Surfactants incorporating natural structural motifs, specifically serine, were chosen instead of the conventional synthetic surfactants, due to the lower cytotoxicity and higher biodegradability, thus being environmentally friendly. Molecular dynamics simulations were performed on 4 systems containing different serine-based surfactants, two of them monomeric (16SerTFA and 12SerTFA) and the other two dimeric ((12ser)2CON12 and (12ser)2N5), in a fully hydrated palmitoyloleoylphosphatidylcholine (POPC) lipid model, intended to mimic cell membranes of both the BBB and tumor. The systems were evaluated in terms of effects induced by the surfactants in this type of membranes and rationalize the interactions at molecular level. The results showed an integration of all surfactants into the POPC membrane. Longer chain length surfactants tended to induce the highest membrane stabilization, as evidenced by 16serTFA. Conversely, the dimeric (12ser)2CON12 led to the greater disturbance in the membrane structure, probably due to bridging phenomena. This may antecipate a better BBB cross ability of LN containing (12ser)2CON12. Overall, this computational study suggests the viability of cationic serine-based surfactants as appealing compounds in LN formulations for targeted GBM therapy