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Morais Catita, Jose Antonio

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  • Nanostructured lipid carriers enriched hydrogels for skin topical administration of quercetin and omega-3 fatty acid
    Publication . Lúcio, Marlene; Giannino, Nicole; Barreira, Sérgio; Catita, José; Gonçalves, Hugo; Ribeiro, Artur; Fernandes, Eduarda; Carvalho, Isabel; Pinho, Hugo; Cerqueira, Fátima; Biondi, Marco; Lopes, Carla Martins
    Chronic skin exposure to external hostile agents (e.g., UV radiation, microorganisms, and oxidizing chemicals) may increase oxidative stress, causing skin damage and aging. Because of their well-known skincare and protective benefits, quercetin (Q) and omega-3 fatty acids (ω3) have attracted the attention of the dermocosmetic and pharmaceutical sectors. However, both bioactives have inherent properties that limit their efficient skin delivery. Therefore, nanostructured lipid carriers (NLCs) and enriched PFC® hydrogels (HGs) have been developed as a dual-approach vehicle for Q and/or ω3 skin topical administration to improve bioactives’ stability and skin permeation. Two NLC formulations were prepared with the same lipid composition but differing in surfactant composition (NLC1—soy lecithin and poloxamer 407; NLC2—Tween® 80 and dioctyl sodium sulfosuccinate (DOSS)), which have an impact on physicochemical properties and pharmaceutical and therapeutic performance. Despite both NLCs presenting high Q loading capacity, NLC2`s physicochemical properties make them more suitable for topical skin administration and ensure longer colloidal stability. Additionally, NLC2 demonstrated a more sustained Q release, indicating higher bioactive storage while improving permeability. The occlusive effect of NLCs-enriched HGs also has a positive impact on skin permeability. Q-loaded NLC2, with or without ω3, -enriched HGs demonstrated efficacy as antioxidant and photoprotective formulations as well as effective reduction in S. aureus growth, indicating that they constitute a promising approach for topical skin administration to prevent skin aging and other damaging cutaneous processes.
  • Formulation, characterization, and cytotoxicity evaluation of lactoferrin functionalized lipid nanoparticles for riluzole delivery to the brain
    Publication . Teixeira, Maria Inês; Lopes, Carla Martins; Gonçalves, Hugo; Catita, José; Silva, Ana Margarida; Rodrigues, Francisca; Amaral, Maria Helena; Costa, Paulo C.
    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a very poor prognosis. Its treatment is hindered by a lack of new therapeutic alternatives and the existence of the blood–brain barrier (BBB), which restricts the access of drugs commonly used in ALS, such as riluzole, to the brain. To overcome these limitations and increase brain targeting, riluzole-loaded nanostructured lipid carriers (NLC) were prepared and functionalized with lactoferrin (Lf), facilitating transport across the BBB by interacting with Lf receptors expressed in the brain endothelium. NLC were characterized with respect to their physicochemical properties (size, zeta potential, polydispersity index) as well as their stability, encapsulation efficiency, morphology, in vitro release profile, and biocompatibility. Moreover, crystallinity and melting behavior were assessed by DSC and PXRD. Nanoparticles exhibited initial mean diameters between 180 and 220 nm and a polydispersity index below 0.3, indicating a narrow size distribution. NLC remained stable over at least 3 months. Riluzole encapsulation efficiency was very high, around 94–98%. FTIR and protein quantification studies confirmed the conjugation of Lf on the surface of the nanocarriers, with TEM images showing that the functionalized NLC presented a smooth surface and uniform spherical shape. An MTT assay revealed that the nanocarriers developed in this study did not cause a substantial reduction in the viability of NSC-34 and hCMEC/D3 cells at a riluzole concentration up to 10 μM, being therefore biocompatible. The results suggest that Lf-functionalized NLC are a suitable and promising delivery system to target riluzole to the brain.
  • Development of lipid-based colloidal nanocarriers for topical application of acyclovir
    Publication . Silva, Juliana; Lopes, Carla Martins; Catita, José; Real Oliveira, Maria Elisabete; Lúcio, Marlene
  • Miconazole-loaded Nanostructured Lipid Carriers (NLC) for local delivery to the oral mucosa: improving antifungal activity
    Publication . Mendes, A.I.; Silva, Ana Catarina; Catita, José; Cerqueira, Fátima; Gabriel, C.; Lopes, Carla Martins
    Miconazole is a widely used antifungal agent with poor aqueous solubility, which requires the development of drug delivery systems able to improve its therapeutic activity. For this purpose, a miconazole-loaded nanostructured lipid carriers (NLC) dispersion was prepared and characterized. Further, the dispersion was used to prepare a NLC-based hydrogel formulation proposed as an alternative system to improve the local delivery of miconazole to the oral mucosa. NLC dispersion showed particles in the nanometer range (≈200 nm) with low polidispersity index (<0.3), good physical stability and high encapsulation efficiency (>87%). A controlled miconazole release was observed from NLC and NLCbased hydrogel formulations, in contrast to a commercial oral gel formulation, which demonstrated a faster release. Additionally, it was observed that the encapsulation of miconazole in the NLC improved its antifungal activity against Candida albicans. Therefore, it was demonstrated that the encapsulation of miconazole in NLC allows for obtaining the same therapeutic effect of a commercial oral gel formulation, using a 17-fold lower dose of miconazole.
  • Omega 3 and resveratrol loaded lipid nanosystems for potential use as topical formulations in autoimmune, inflammatory, and cancerous skin diseases
    Publication . Caldas, Ana Rita; Catita, José; Machado, Raúl; Ribeiro, Artur; Cerqueira, Fátima; Horta, Bruno; Medeiros, R.; Lúcio, Marlene; Lopes, Carla Martins
    Resveratrol (RSV) and omega 3 (ω3), because of their biological favorable properties, have become subjects of interest for researchers in dermocosmetic and pharmaceutical industries; however, these bioactives present technological limitations that hinder their effective delivery to the target skin layer. To overcome the stability and skin permeation limitations of free bioactives, this work proposes a combined strategy involving two different lipid nanosystems (liposomes and lipid nanoparticles) that include ω3 in their lipid matrix. Additionaly, RSV is only encapsulated in liposomes that provid an adequate amphiphilic environment. Each formulation is thoroughly characterized regarding their physical–chemical properties. Subsequently, the therapeutic performance of the lipid nanosystems is evaluated based on their protective roles against lipid peroxidation, as well as inhibition of cicloxygenase (COX) and nitric oxid (NO) production in the RWA264.7 cell line. Finally, the lipid nanosystems are incorporated in hydrogel to allow their topical administration, then rheology, occlusion, and RSV release–diffusion assays are performed. Lipid nanoparticles provide occlusive effects at the skin surface. Liposomes provide sustained RSV release and their flexibility conferred by edge activator components enhances RSV diffusion, which is required to reach NO production cells and COX cell membrane enzymes. Overall, the inclusion of both lipid nanosystems in the same semisolid base constitutes a promising strategy for autoimmune, inflammatory, and cancerous skin diseases.
  • Riluzole-loaded lipid nanoparticles for brain delivery: preparation, optimization and characterization
    Publication . Teixeira, Maria Inês; Lopes, Carla Martins; Gonçalves, Hugo; Catita, José; Silva, Ana Margarida; Rodrigues, Francisca; Amaral, Maria Helena; Costa, Paulo C.
    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, with a median survival of only 2 to 4 years. Riluzole, a drug commonly used in the management of ALS, has a low aqueous solubility and limited bioavailability. ALS treatment is also hindered by the presence of the blood–brain barrier (BBB) that preserves the delicate homeostasis of the cerebral milieu, isolating it and making brain drug delivery exceptionally hard. To overcome these issues, the use of lipid nanocarriers, such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), is a promising strategy. In this study, SLN and NLC were prepared and optimized to facilitate riluzole uptake into the brain for ALS therapy. The lipid nanoparticles were characterized through different techniques, with respect to their physicochemical properties (size, zeta potential (ZP), polydispersity index (PDI)), as well as encapsulation efficiency, morphology, stability, in vitro release, crystallinity, and biocompatibility. Riluzole-loaded nanocarriers exhibited characteristics suitable for brain delivery, including mean diameters between 147.2 and 203.1 nm, low PDI (<0.3), and negative ZP between − 22.5 and − 27.5 mV. Additionally, they were physically stable over 3 months under storage conditions (5 ℃ and 25 ℃), promoting a slow and sustained release of the drug, which was shown to be inside the core of the lipid matrix. Cytotoxicity assays demonstrated that both SLN and NLC did not significantly affect the viability of an hCMEC/D3 cell monolayer at a riluzole concentration up to 10 μM. The results suggest that the developed nanocarriers could be a viable platform to target riluzole to the central nervous system (CNS). Nevertheless, further in vitro and in vivo studies are needed to validate their therapeutic efficacy and safety.
  • Personalised esomeprazole and ondansetron 3D printing formulations in Hospital Paediatric Environment: I-pre-formulation studies
    Publication . Ferreira, Mariana; Lopes, Carla Martins; Gonçalves, Hugo; Pinto, João F.; Catita, José
    Individualised medicine demands the formulation of pharmacotherapy in accordance with the characteristics of each patient’s health condition, and paediatrics is one of the areas that needs this approach. The 3D printing of oral doses is one method for achieving customised medicine in paediatrics. In this work, pre-formulation studies were conducted to evaluate the viability of using specific raw materials to produce 3D printed dosage forms based on two active pharmaceutical ingredients (APIs), ondansetron and esomeprazole, which are important for therapeutic customisation in paediatrics. Pre-formulation studies were carried out by characterising the physical and chemical properties of selected raw materials, selected APIs and their mixtures, using analytical methods such as scanning electron microscopy (SEM), X-ray powder diffraction (X-RPD), simultaneous thermal analysis (STA) and differential scanning calorimetry (DSC). The flowability of powders, compatibility and stability studies were also performed. Among all the ingredients selected, the PVPs (K17, K25 and K90) had the best characteristics to incorporate both forms of Esomeprazole Mg in a formulation to produce extrudates. The results obtained validated the use of some selected raw materials for tablet manufacture by the 3D printing approach.