Percorrer por autor "Costa, Paulo C."
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- Compressed matrix core tablet as a quick/slow dual-component delivery system containing ibuprofenPublication . Lopes, Carla Martins; Lobo, José M. Sousa; Pinto, João F.; Costa, Paulo C.The purpose of the present research was to produce a quick/slow biphasic delivery system for ibuprofen. A dualcomponent tablet made of a sustained release tableted core and an immediate release tableted coat was prepared by direct compression. Both the core and the coat contained a model drug (ibuprofen). The sustained release effect was achieved with a polymer (hydroxypropyl methylcellulose [HPMC] or ethylcellulose) to modulate the release of the drug. The in vitro drug release profile from these tablets showed the desired biphasic release behavior: the ibuprofen contained in the fast releasing component was dissolved within 2 minutes, whereas the drug in the core tablet was released at different times (≈16 or 924 hours), depending on the composition of the matrix tablet. Based on the release kinetic parameters calculated, it can be concluded that the HPMC core was suitable for providing a constant and controlled release (zero order) for a long period of time.
- Current insights on lipid nanocarrier-assisted drug delivery in the treatment of neurodegenerative diseasesPublication . Lopes, Carla Martins; Amaral, Maria Helena Amaral; Costa, Paulo C.The central nervous system (CNS) is vulnerable to pathologic processes that lead to the development of neurodegenerative disorders like Alzheimer’s, Parkinson’s and Huntington’s diseases, Multiple sclerosis or Amyotrophic lateral sclerosis. These are chronic and progressive pathologies characterized by the loss of neurons and the formation of misfolded proteins. Additionally, neurodegenerative diseases are accompanied by a structural and functional dysfunction of the blood-brain barrier (BBB). Although serving as a protection for CNS, the existence of physiological barriers, especially the BBB, limits the access of several therapeutic agents to the brain, constituting a major hindrance in neurotherapeutics advancement. In this regard, nanotechnology-based approaches have arisen as a promising strategy to not only improve drug targeting to the brain, but also to increase bioavailability. Lipid nanocarriers such as liposomes, solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), microemulsions and nanoemulsions, have already proven their potential for enhancing brain transport, crossing more easily into the CNS and allowing the administration of medicines that could benefit the treatment of neurological pathologies. Given the socioeconomic impact of such conditions and the advent of nanotechnology that inevitably leads to more effective and superior therapeutics for their management, it is imperative to constantly update on the current knowledge of these topics. Herein, we provide insight on the BBB and the pathophysiology of the main neurodegenerative disorders. Moreover, this review seeks to highlight the several approaches that can be used to improve the delivery of therapeutic agents to the CNS, while also offering an extensive overview of the latest efforts regarding the use of lipid-based nanocarriers in the management of neurodegenerative diseases.
- Formulation, characterization, and cytotoxicity evaluation of lactoferrin functionalized lipid nanoparticles for riluzole delivery to the brainPublication . 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.
- Permeability assay and inflammatory marker quantification of lactoferrin functionalized lipid nanoparticles intended for brain deliveryPublication . Teixeira, Maria Inês; Lopes, Carla Martins; Reguengo, Henrique; Oliveira, José Carlos; Silva, Ana Margarida; Rodrigues, Francisca; Amaral, Maria Helena; Costa, Paulo C.Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a survival rate of 3 to 5 years from the onset of symptoms. ALS treatment is compromised by the existence of the blood-brain barrier (BBB), which restricts the access of promising biopharmaceutics to the brain, including riluzole, a drug commonly used to treat ALS. To circumvent the BBB and improve the drug brain targeting, nanosystems such as lipid nanoparticles can be employed. In this work, the permeation of nanostructured lipid carriers (NLC) loaded with riluzole and functionalized with a specific ligand – lactoferrin – was assessed in an in vitro BBB model (hCMEC/D3 cell line). Moreover, the effect of the NLC on the production and secretion of the pro-inflammatory cytokine human interleukin 1 alpha (IL-1a) by the cells was also quantified. The permeability studies across the hCMEC/D3 cell monolayers showed that free riluzole penetrated the BBB more than the riluzole-loaded NLC, which was also consistent with the results from the ELISA kit, with the free drug eliciting a higher IL-1a production. Despite these findings, the developed nanocarriers possessed good biocompatibility and stability, and could, therefore, be considered suitable for brain applications.
- Riluzole-loaded lipid nanoparticles for brain delivery: preparation, optimization and characterizationPublication . 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.
- Silver nanoparticles for the management of neurological diseasesPublication . Teixeira, Maria Inês; Lopes, Carla Martins; Amaral, Maria Helena; Costa, Paulo C.
- Surface-modified lipid nanocarriers for crossing the blood-brain barrier (BBB): a current overview of active targeting in brain diseasesPublication . Teixeira, Maria Inês; Lopes, Carla Martins; Amaral, Maria Helena; Costa, Paulo C.The blood-brain barrier (BBB) restricts the access of therapeutic agents to the brain, complicating the treatment of neurological diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), glioma, etc. To overcome this limitation and improve drug delivery to the central nervous system (CNS), the potential of nanocarriers, including lipid-based nanosystems, has been explored. Through active targeting, the surface of the nanocarriers can be modified with ligands that interact with the BBB, enhancing their uptake and penetration across the brain endothelium by different physiological mechanisms, such as receptor- or transporter-mediated transcytosis. This review seeks to provide an overview of active targeting in brain delivery, while highlighting the potential of functionalized lipid nanocarriers to treat brain diseases. Therefore, in the first sections, we discuss the importance of active targeting in CNS drug delivery, present the different ligands commonly used for functionalization, as well as summarize the state of the art of the most recent and relevant studies of surface-modified lipid nanosystems developed for neurological disorders. Lastly, challenges hindering clinical translation are discussed, and critical insights and future perspectives outlined. Although some limitations have been identified, it is expected that in the upcoming years these nanosystems will be an established approach.