Publications

Malaria, caused by different species of protists of the genus Plasmodium, remains among the most common causes of death due to parasitic diseases worldwide, mainly for children aged under 5. One of the main obstacles to malaria eradication is the speed with which the pathogen evolves resistance to the drug schemes developed against it. For this reason, it remains urgent to find innovative therapeutic strategies offering sufficient specificity against the parasite to minimize resistance evolution and drug side effects. In this context, nanotechnology-based approaches are now being explored for their use as antimalarial drug delivery platforms due to the wide range of advantages and tuneable properties that they offer. However, major challenges remain to be addressed to provide a cost-efficient and targeted therapeutic strategy contributing to malaria eradication. The present work contains a systematic review of nanotechnology-based antimalarial drug delivery systems generated during the last 10 years. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease

JTD Keywords: Antimalarial agent, Antimalarial drug, Antimalarial drugs, Antimalarial drugs,malaria vaccine,nanotechnology,nanocarriers,nanomedicine,plasmodium,targeted drug deliver, Antimalarials, Causes of death, Child, Controlled drug delivery, Diseases, Drug delivery system, Drug delivery systems, Drug interactions, Drug side-effects, Experimental modelling, Human, Humans, Malaria, Malaria vaccine, Medical nanotechnology, Models, theoretical, Nanocarriers, Nanomedicine, Nanotechnology, Parasite-, Parasitics, Plasmodium, Red-blood-cells,plasmodium-falciparum malaria,drug-delivery,in-vitro,heparan-sulfate,antimalarial activities,mannosylated liposomes,artemisinin resistance,targeted delivery,adjuvant syste, Targeted drug delivery, Theoretical model, Therapeutic strategy

Lysosomes play a central role in cellular homeostasis and alterations in this compartment associate with many diseases. The most studied example is that of lysosomal storage disorders (LSDs), a group of 60 + maladies due to genetic mutations affecting lysosomal components, mostly enzymes. This leads to aberrant intracellular storage of macromolecules, altering normal cell function and causing multiorgan syndromes, often fatal within the first years of life. Several treatment modalities are available for a dozen LSDs, mostly consisting of enzyme replacement therapy (ERT) strategies. Yet, poor biodistribution to main targets such as the central nervous system, musculoskeletal tissue, and others, as well as generation of blocking antibodies and adverse effects hinder effective LSD treatment. Drug delivery systems are being studied to surmount these obstacles, including polymeric constructs and nanoparticles that consti-tute the focus of this article. We provide an overview of the formulations being tested, the diseases they aim to treat, and the results observed from respective in vitro and in vivo studies. We also discuss the advantages and disadvantages of these strategies, the remaining gaps of knowledge regarding their per-formance, and important items to consider for their clinical translation. Overall, polymeric nanocon-structs hold considerable promise to advance treatment for LSDs.(c) 2023 Elsevier B.V. All rights reserved.

JTD Keywords: cellular and animal models, enzyme replacement therapy, lysosomal storage disorders, nanoemulsions, nanoparticles, Beta-glucuronidase deficiency, Blood-brain-barrier, Cellular and animal models, Central-nervous-system, Enzyme replacement therapy, Feline gm1 gangliosidosis, Human acid sphingomyelinase, Human alpha-galactosidase, Lysosomal storage disorders, Mucopolysaccharidosis type-ii, Nanoemulsions, Nanoparticles, Neuronal ceroid-lipofuscinosis, Niemann-pick-disease, Pluripotent stem-cells, Polymer-based drug delivery systems

In this study, we assessed the capacity of a previously reported engineered liposomal formulation, which had been tested against model membranes mimicking the lipid composition of the HeLa plasma membrane, to fuse and function as a nanocarrier in cells. We used atomic force microscopy to observe physicochemical changes on the cell surface and confocal microscopy to determine how the liposomes interact with cell membranes and released their load. In addition, we performed viability assays using methotrexate as an active drug to obtain proof of concept of the formulation´s capacity to function as a drug delivery-system. The interaction of engineered liposomes with living cells corroborates the information obtained using model membranes and supports the capacity of the engineered liposomal formulation to serve as a potential nanocarrier.Copyright © 2022 Elsevier B.V. All rights reserved.

JTD Keywords: atomic force microscopy, confocal microscopy, drug delivery system, filopodia, young ?s modulus, Atomic force microscopy, Confocal microscopy, Drug delivery system, Engineered liposomes, Filopodia, Young´s modulus

Local cancer treatment by in situ injections of thermo-responsive hydrogels (HG) offers several advantages over conventional systemic anti-cancer treatments. In this work, a biodegradable and multicompartmental HG composed of N-isopropylacrylamide, cellulose, citric acid, and ceric ammonium nitrate was developed for the controlled release of hydrophilic (doxorubicin) and hydrophobic (niclosamide) drugs. The formulation presented ideal properties regarding thermo-responsiveness, rheological behavior, drug release profile, biocompatibility, and biological activity in colon and ovarian cancer cells. Cellulose was found to retard drugs release rate, being only 4 % of doxorubicin and 30 % of niclosamide released after 1 week. This low release was sufficient to cause cell death in both cell lines. Moreover, HG demonstrated a proper injectability, in situ prevalence, and safety profile in vivo. Overall, the HG properties, together with its natural and eco-friendly composition, create a safe and efficient platform for the local treatment of non-resectable tumors or tumors requiring pre-surgical adjuvant therapy.

JTD Keywords: biodegradable, cellulose, controlled-release formulation, drug delivery systems, hydrogel, thermo-responsiveness, Ammonium-nitrate, Biodegradable, Cancer treatment, Cellulose, Controlled-release formulation, Delivery, Drug delivery systems, Hydrogel, Reduce, Thermo-responsiveness

A plethora of applications using polysaccharides have been developed in recent years due to their availability as well as their frequent nontoxicity and biodegradability. These polymers are usually obtained from renewable sources or are byproducts of industrial processes, thus, their use is collaborative in waste management and shows promise for an enhanced sustainable circular economy. Regarding the development of novel delivery systems for biotherapeutics, the potential of polysaccharides is attractive for the previously mentioned properties and also for the possibility of chemical modification of their structures, their ability to form matrixes of diverse architectures and mechanical properties, as well as for their ability to maintain bioactivity following incorporation of the biomolecules into the matrix. Biotherapeutics, such as proteins, growth factors, gene vectors, enzymes, hormones, DNA/RNA, and antibodies are currently in use as major therapeutics in a wide range of pathologies. In the present review, we summarize recent progress in the development of polysaccharide-based hydrogels of diverse nature, alone or in combination with other polymers or drug delivery systems, which have been implemented in the delivery of biotherapeutics in the pharmaceutical and biomedical fields. © 2021 American Chemical Society.

JTD Keywords: biodegradable dextran hydrogels, biotherapeutics, bone morphogenetic protein-2, carrageenan-based hydrogels, chitosan-based hydrogels, controlled delivery, controlled-release, cross-linked hydrogels, growth-factor delivery, hydrogels, in-vitro characterization, polysaccharides, self-healing hydrogel, stimuli-responsiveness, tissue engineering, Antibodies, Bioactivity, Biodegradability, Biomedical fields, Biomolecules, Biotherapeutics, Chemical modification, Circular economy, Controlled delivery, Controlled drug delivery, Delivery systems, Drug delivery system, Functional polymers, Hyaluronic-acid hydrogels, Hydrogels, Industrial processs, Polysaccharides, Recent progress, Renewable sources, Stimuli-responsiveness, Targeted drug delivery, Tissue engineering, Waste management

A new methodology for the pH-triggered degradation of polymers or for the release of drugs under visible light irradiation based on the cyclization of ortho-hydroxy-cinnamates (oHC) to coumarins is described. The key oHC structural motif can be readily incorporated into the rational design of novel photocleavable polymers via click chemistry. This main-chain moiety undergoes a fast photocleavage when irradiated with 455 nm light provided that a suitable base is added. A series of polyethylene glycol-alt-ortho-hydroxy cinnamate (polyethylene glycol (PEG)(n)-alt-oHC)-based polymers are synthesized and the time-dependent visible-light initiated cleavage of the photoactive monomer and polymer is investigated in solution by a variety of spectroscopic and chromatographic techniques. The photo-degradation behavior of the water-soluble poly(PEG(2000)-alt-oHC) is investigated within a broad pH range (pH = 2.1-11.8), demonstrating fast degradation at pH 11.8, while the stability of the polymer is greatly enhanced at pH 2.1. Moreover, the neat polymer shows long-term stability under daylight conditions, thus allowing its storage without special precautions. In addition, two water-soluble PEG-based drug-carrier molecules (mPEG(2000)-oHC-benzhydrol/phenol) are synthesized and used for drug delivery studies, monitoring the process by UV-vis spectroscopy in an ON/OFF intermittent manner.

JTD Keywords: coumarins, drug delivery, e/z-double bond isomerization, o-hydroxy cinnamates, polymer degradation, Aliphatic compounds, Antioxidant activity, Antitumor, Chromatographic techniques, Chromatography, Cis/trans isomerization, Controlled drug delivery, Coumarin derivatives, Coumarins, Drug delivery, Drug delivery system, E/z-double bond isomerization, Films, Hydrogels, Image enhancement, Light, Long term stability, O-hydroxy cinnamates, Particles, Photoactive monomers, Photodegradation, Polyethylene glycols, Polyethylenes, Polymer degradation, Responsive polymers, Salts, Structural motifs, Synthesis (chemical), Targeted drug delivery, Visible light photocatalysis, Visible-light irradiation

Endocytosis and vesicular trafficking are cellular processes that regulate numerous functions required to sustain life. From a translational perspective, they offer avenues to improve the access of therapeutic drugs across cellular barriers that separate body compartments and into diseased cells. However, the fact that many factors have the potential to alter these routes, impacting our ability to effectively exploit them, is often overlooked. Altered vesicular transport may arise from the molecular defects underlying the pathological syndrome which we aim to treat, the activity of the drugs being used, or side effects derived from the drug carriers employed. In addition, most cellular models currently available do not properly reflect key physiological parameters of the biological environment in the body, hindering translational progress. This article offers a critical overview of these topics, discussing current achievements, limitations and future perspectives on the use of vesicular transport for drug delivery applications.

JTD Keywords: Cellular vesicles, Vesicle fusion, Fission and intracellular trafficking, Drug delivery systems and nanomedicines, Transcytosis and endocytosis of drugs carriers, Disease effects on vesicular trafficking, Drug effects on vesicular trafficking, Role of the biological environment

JTD Keywords: antimalarial, heparin, magic bullet, malaria, nanomedicine, nanotechnology, nanovector, Plasmodium, polymers, targeted drug delivery, chloroquine, immunoliposome, liposome, nanoparticle, solid lipid nanoparticle, Anopheles, antimalarial activity, drug delivery system, drug efficacy, erythrocyte, human, IC50, malaria, malaria control, nanoencapsulation, nonhuman, pathophysiology, Plasmodium, Review