Papers by Eva Gil Martins
Pharmaceutics
The intranasal route has been suggested as a promising alternative to improve the direct transpor... more The intranasal route has been suggested as a promising alternative to improve the direct transport of molecules to the brain, avoiding the need to cross the blood–brain barrier (BBB). In this area, the use of lipid nanoparticles, namely solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), has been highlighted as a promising strategy to improve the treatment of neurodegenerative diseases. In this work, formulations containing SLN and NLC that were loaded with astaxanthin that was obtained from different sources (astaxanthin extract (AE) from the algae Haematococcus pluvialis and pure astaxanthin (PA) from the fungi Blakeslea trispora) were prepared for nose-to-brain administration, and comparative in vitro experiments were performed to evaluate the biocompatibility of the formulations with nasal (RPMI 2650) and neuronal (SH-SY5Y) cells. Afterwards, the antioxidant activity of the formulations was evaluated for its potential neuroprotective effects, using different...
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Chemical Communications
A novel route is described to obtain antimicrobial 2-aminoimidazole azo dyes with a unique substi... more A novel route is described to obtain antimicrobial 2-aminoimidazole azo dyes with a unique substituent pattern in the heteroaryl unit that provides halochromic properties, exhibiting vibrant colours that change from magenta to deep blue.
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RevSALUS - Revista Científica da Rede Académica das Ciências da Saúde da Lusofonia, 2022
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Expert Opinion on Drug Metabolism & Toxicology, 2021
ABSTRACT Introduction: P-glycoprotein (P-gp) is an important efflux pump responsible for the extr... more ABSTRACT Introduction: P-glycoprotein (P-gp) is an important efflux pump responsible for the extruding of many endogenous and exogenous substances out of the cells. P-gp can be modulated by different molecules – including xanthone derivatives – to surpass the multidrug resistance (MDR) phenomenon through P-gp inhibition, or to serve as an antidotal strategy in intoxication scenarios through P-gp induction/activation. Areas covered: This review provides a perspective on P-gp modulators, with particular focus on xanthonic derivatives, highlighting their ability to modulate P-gp expression and/or activity, and the potential impact of these effects on the pharmacokinetics, pharmacodynamics and toxicity of P-gp substrates. Expert opinion: Xanthones, of natural or synthetic origin, are able to modulate P-gp, interfering with its protein synthesis or with its mechanism of action, by decreasing or increasing its efflux capacity. These modulatory effects make the xanthonic scaffold a promising source of new derivatives with therapeutic potential. However, the mechanisms beyond the xanthones-mediated P-gp modulation and the chemical characteristics that make them more potent P-gp inhibitors or inducers/activators are still understudied. Furthermore, a new window of opportunity exists in the neuropathologies field, where xanthonic derivatives with potential to modulate P-gp should be further explored to optimize the prevention/treatment of brain pathologies. GRAPHICAL ABSTRACT
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Toxicology Letters, 2021
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International Journal of Pharmaceutics, 2021
Diazepam is commonly used in the management of epileptic seizures, although it has limitations th... more Diazepam is commonly used in the management of epileptic seizures, although it has limitations that can be overcome by using formulations that are easier to administer and capable of directing the drug to the brain. In this field, it has been reported that the use of nanostructured lipid carriers (NLC) via intranasal (or via nose-to-brain) promotes the targeting of drugs to the brain, improving the effectiveness of therapy. The aim of this work was to optimize two diazepam-loaded NLC formulations for nose-to-brain delivery, one with positive surface charge and one with negative surface charge. The quality by design (QbD) approach was used to design the experiments, where the quality target product profile (QTPP), the risk assessment and the critical quality attributes (CQAs) were defined to ensure safety, efficacy and quality of the final formulations. The experiments started with the optimization of critical material attributes (CMAs), related to the ratios of lipids and emulsifiers, followed by the selection of critical process parameters (CPPs), related to the production methods of the diazepam-loaded NLC formulation (ultrasound technique and high-pressure homogenization - HPH). Afterwards, the positive surface charge of the diazepam-loaded NLC was optimized. Finally, the biocompatibility with human neuronal cells of the formulation with a negative surface charge and of the formulation with a positive surface charge was evaluated. The results of the optimization of the CMAs showed that the ratios of lipids and emulsifiers more adequate were 6.7:2.9 and 4.2:0.3 (% w,w), respectively. Regarding the CPPs, HPH was considered the most suitable production method, resulting in an optimized diazepam-loaded NLC formulation (F1C15) with negative surface charge, showing particle size of 69.59±0.22 nm, polydispersity index (PDI) of 0.19±0.00, zeta potential (ZP) of -23.50±0.24 mV and encapsulation efficiency (EE) of 96.60±0.03 %. The optimized diazepam-loaded NLC formulation (F2A8) with positive surface charge had particle size of 124.40±0.84 nm, PDI of 0.17±0.01, ZP of 32.60±1.13 mV and EE of 95.76±0.24 %. In addition, the incorporation of diazepam in NLC resulted in a sustained release of the drug. No significant changes in particle size, PDI, ZP and EE were observed for the formulation F1C15, after 3 months of storage, whereas for formulation F2A8, particle size increased significantly. Biocompatibility studies showed that the formulation F2A8 was more cytotoxic than the formulation F1C15. Thereby, we conclude that the formulation F1C15 is more suitable for targeting the brain, when compared with the formulation F2A8. From the results of these studies, it can be confirmed that the QbD approach is an adequate and central tool to optimize NLC formulations.
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Medicinal Chemistry Research, 2020
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Pharmacology & Therapeutics, 2020
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European Journal of Medicinal Chemistry, 2019
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Papers by Eva Gil Martins