Publications by authors named "Gustavo Lou"

Article Synopsis
  • Current SARS-CoV-2 mRNA vaccines are effective, but there's a need for new strategies due to waning immunity and variant emergence, prompting this study on a heterologous mRNA/MVA vaccination approach.
  • The research demonstrates that a combination of a trimeric receptor binding domain (RBD) delivered via mRNA and a modified vaccinia virus (MVA) boost creates strong immune responses, including effective antibodies and T cell activity against various SARS-CoV-2 strains.
  • The heterologous regimen provided complete protection in specific mouse models after exposure to the virus, outperforming traditional methods and suggesting that alternative nanocarrier technologies could enhance vaccine effectiveness while avoiding patent issues.
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The global emergency of coronavirus disease 2019 (COVID-19) has spurred extensive worldwide efforts to develop vaccines for protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our contribution to this global endeavor involved the development of a diverse library of nanocarriers, as alternatives to lipid nanoparticles (LNPs), including nanoemulsions (NEs) and nanocapsules (NCs), with the aim of protecting and delivering messenger ribonucleic acid (mRNA) for nasal vaccination purposes. A wide range of prototypes underwent rigorous screening through a series of in vitro and in vivo experiments, encompassing assessments of cellular transfection, cytotoxicity, and intramuscular administration of a model mRNA for protein translation.

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Article Synopsis
  • - Vaccines using mRNA technology, particularly lipid nanoparticles (LNP), are key in combating SARS-CoV-2 and have applications for other diseases too.
  • - The study tested various lipid and polymer-based nanoparticles for delivering mRNA that encodes a part of the spike protein from SARS-CoV-2, assessing their toxicity and effectiveness in animal models.
  • - Results showed that modified lipid nanoparticles (mLNP) and traditional LNP-1 were highly effective in producing antibodies and protecting mice from COVID-19, suggesting alternative carriers can enhance mRNA vaccine performance.
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The efficacy of RNA-based vaccines has been recently demonstrated, leading to the use of mRNA-based COVID-19 vaccines. The application of self-amplifying mRNA within these formulations may offer further enhancement to these vaccines, as self-amplifying mRNA replicons enable longer expression kinetics and more potent immune responses compared to non-amplifying mRNAs. To investigate the impact of administration route on RNA-vaccine potency, we investigated the immunogenicity of a self-amplifying mRNA encoding the rabies virus glycoprotein encapsulated in different nanoparticle platforms (solid lipid nanoparticles (SLNs), polymeric nanoparticles (PNPs) and lipid nanoparticles (LNPs)).

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In the recent of years, the use of lipid nanoparticles (LNPs) for RNA delivery has gained considerable attention, with a large number in the clinical pipeline as vaccine candidates or to treat a wide range of diseases. Microfluidics offers considerable advantages for their manufacture due to its scalability, reproducibility and fast preparation. Thus, in this study, we have evaluated operating and formulation parameters to be considered when developing LNPs.

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Self-amplifying RNA (SAM) represents a versatile tool that can be used to develop potent vaccines, potentially able to elicit strong antigen-specific humoral and cellular-mediated immune responses to virtually any infectious disease. To protect the SAM from degradation and achieve efficient delivery, lipid nanoparticles (LNPs), particularly those based on ionizable amino-lipids, are commonly adopted. Herein, we compared commonly available cationic lipids, which have been broadly used in clinical investigations, as an alternative to ionizable lipids.

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messenger RNA (mRNA)-based vaccines combine the positive attributes of both live-attenuated and subunit vaccines. In order for these to be applied for clinical use, they require to be formulated with delivery systems. However, there are limited in vivo studies which compare different delivery platforms.

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Article Synopsis
  • Nanomedicines help improve treatments for diseases but are hard and expensive to produce with old methods.
  • This study looks at a new way to make nanomedicines using special devices called microfluidic cartridges that can produce large amounts quickly and consistently.
  • By testing different designs, researchers found a way to make liposomes (tiny drug carriers) faster and with better quality, making it easier to create products for patients effectively.
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Background: Solid lipid nanoparticles offer a range of advantages as delivery systems but they are limited by effective manufacturing processes.

Objective: In this study, we outline a high-throughput and scalable manufacturing process for solid lipid nanoparticles.

Methods: The solid lipid nanoparticles were formulated from a combination of tristearin and 1,2-Distearoyl-phosphatidylethanolamine-methyl-polyethyleneglycol conjugate-2000 and manufactured using the M-110P Microfluidizer processor (Microfluidics Inc, Westwood, Massachusetts, US).

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Article Synopsis
  • Scientists studied how the size of tiny bubbles called liposomes affects their behavior in lab tests (in vitro) and in living things (in vivo).
  • They found that using a new technique called microfluidics made it easier to create liposomes of different sizes that were all the same and worked better than older methods.
  • Their research showed that small and big liposomes can enter certain cells similarly, but their sizes change how many liposomes get taken in and where they go in the body, especially in mice.
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Mannosylation of Lipid Nanoparticles (LNP) can potentially enhance uptake by Antigen Presenting Cells, which are highly abundant in dermal tissues, to improve the potency of Self Amplifying mRNA (SAM) vaccines in comparison to the established unmodified LNP delivery system. In the current studies, we evaluated mannosylated LNP (MLNP), which were obtained by incorporation of a stable Mannose-cholesterol amine conjugate, for the delivery of an influenza (hemagglutinin) encoded SAM vaccine in mice, by both intramuscular and intradermal routes of administration. SAM MLNP exhibited enhanced uptake in comparison to unglycosylated LNP from bone marrow-derived dendritic cells, and more rapid onset of the antibody response, independent of the route.

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In vitro experiments have shown the great potential of magnetic nanocarriers for multimodal imaging diagnosis and non-invasive therapies. However, their extensive clinical application is still jeopardized by a fast retention in the reticuloendothelial system (RES). The other issue that restrains their potential performance is slow degradation and excretion, which increases their risks of toxicity.

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At present, bioferrofluids are employed as powerful multifunctional tools for biomedical applications such as drug delivery, among others. The present study explores the cellular response evoked when bile-acid platinum derivatives are conjugated with bioferrofluids by testing the biological activity in osteosarcoma (MG-63) and T-cell leukemia (Jurkat) cells. The aim of this work is to evaluate the biocompatibility of a bile-acid platinum derivative conjugated with multi-functional polymer coated bioferrofluids by observing the effects on the protein expression profiles and in intracellular pathways of nanoparticle-stimulated cells.

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