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1. Chronic cholesterol administration to the brain supports complete and long-lasting cognitive and motor amelioration in Huntington’s disease

Author

Birolini, Giulia, Valenza, Marta, Ottonelli, Ilaria, Talpo, Francesca, Minoli, Lucia, Cappelleri, Andrea, Bombaci, Mauro, Caccia, Claudio, Canevari, Caterina, Trucco, Arianna, Leoni, Valerio, Passoni, Alice, Favagrossa, Monica, Nucera, Maria Rosaria, Colombo, Laura, Paltrinieri, Saverio, Bagnati, Renzo, Duskey, Jason Thomas, Caraffi, Riccardo, Vandelli, Maria Angela, Taroni, Franco, Salmona, Mario, Scanziani, Eugenio, Biella, Gerardo, Ruozi, Barbara, Tosi, Giovanni, and Cattaneo, Elena

Published
2023
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4. Cholesterol‐loaded nanoparticles ameliorate synaptic and cognitive function in Huntington's disease mice

Author

Valenza, Marta, Chen, Jane Y, Di Paolo, Eleonora, Ruozi, Barbara, Belletti, Daniela, Ferrari Bardile, Costanza, Leoni, Valerio, Caccia, Claudio, Brilli, Elisa, Di Donato, Stefano, Boido, Marina M, Vercelli, Alessandro, Vandelli, Maria A, Forni, Flavio, Cepeda, Carlos, Levine, Michael S, Tosi, Giovanni, and Cattaneo, Elena

Subjects
Biochemistry and Cell Biology, Biological Sciences, Huntington's Disease, Neurosciences, Brain Disorders, Rare Diseases, Biotechnology, Nanotechnology, Neurodegenerative, Bioengineering, Aetiology, 2.1 Biological and endogenous factors, Neurological, Animals, Blood-Brain Barrier, Cholesterol, Cognition, Disease Models, Animal, Huntington Disease, Mice, Nanoparticles, Neurons, Synapses, cholesterol, cognition, Huntington's disease, nanoparticles, synapses, Medical and Health Sciences, Biochemistry and cell biology
Abstract

Brain cholesterol biosynthesis and cholesterol levels are reduced in mouse models of Huntington's disease (HD), suggesting that locally synthesized, newly formed cholesterol is less available to neurons. This may be detrimental for neuronal function, especially given that locally synthesized cholesterol is implicated in synapse integrity and remodeling. Here, we used biodegradable and biocompatible polymeric nanoparticles (NPs) modified with glycopeptides (g7) and loaded with cholesterol (g7-NPs-Chol), which per se is not blood-brain barrier (BBB) permeable, to obtain high-rate cholesterol delivery into the brain after intraperitoneal injection in HD mice. We report that g7-NPs, in contrast to unmodified NPs, efficiently crossed the BBB and localized in glial and neuronal cells in different brain regions. We also found that repeated systemic delivery of g7-NPs-Chol rescued synaptic and cognitive dysfunction and partially improved global activity in HD mice. These results demonstrate that cholesterol supplementation to the HD brain reverses functional alterations associated with HD and highlight the potential of this new drug-administration route to the diseased brain.

Published
2015

5. “Combo” Multi-Target Pharmacological Therapy and New Formulations to Reduce Inflammation and Improve Endogenous Remyelination in Traumatic Spinal Cord Injury

Author

Moretti, Marzia, primary, Caraffi, Riccardo, additional, Lorenzini, Luca, additional, Ottonelli, Ilaria, additional, Sannia, Michele, additional, Alastra, Giuseppe, additional, Baldassarro, Vito Antonio, additional, Giuliani, Alessandro, additional, Duskey, Jason Thomas, additional, Cescatti, Maura, additional, Ruozi, Barbara, additional, Aloe, Luigi, additional, Vandelli, Maria Angela, additional, Giardino, Luciana, additional, Tosi, Giovanni, additional, and Calzà, Laura, additional

Published
2023
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8. Optimization of an Injectable Hydrogel Depot System for the Controlled Release of Retinal-Targeted Hybrid Nanoparticles

Author

Ottonelli, Ilaria, primary, Bighinati, Andrea, additional, Adani, Elisa, additional, Loll, François, additional, Caraffi, Riccardo, additional, Vandelli, Maria Angela, additional, Boury, Frank, additional, Tosi, Giovanni, additional, Duskey, Jason Thomas, additional, Marigo, Valeria, additional, and Ruozi, Barbara, additional

Published
2022
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11. Optimization of an Injectable Hydrogel Depot System for the Controlled Release of Retinal-Targeted Hybrid Nanoparticles.

Author

Ottonelli, Ilaria, Bighinati, Andrea, Adani, Elisa, Loll, François, Caraffi, Riccardo, Vandelli, Maria Angela, Boury, Frank, Tosi, Giovanni, Duskey, Jason Thomas, Marigo, Valeria, and Ruozi, Barbara

Subjects
INTRAVITREAL injections, HYDROGELS, RETINAL diseases, NANOPARTICLES, HYALURONIC acid, THERAPEUTICS
Abstract

A drawback in the development of treatments that can reach the retina is the presence of barriers in the eye that restrain compounds from reaching the target. Intravitreal injections hold promise for retinal delivery, but the natural defenses in the vitreous can rapidly degrade or eliminate therapeutic molecules. Injectable hydrogel implants, which act as a reservoir, can allow for long-term drug delivery with a single injection into the eye, but still suffer due to the fast clearance of the released drugs when traversing the vitreous and random diffusion that leads to lower pharmaceutic efficacy. A combination with HA-covered nanoparticles, which can be released from the gel and more readily pass through the vitreous to increase the delivery of therapeutic agents to the retina, represents an advanced and elegant way to overcome some of the limitations in eye drug delivery. In this article, we developed hybrid PLGA-Dotap NPs that, due to their hyaluronic acid coating, can improve in vivo distribution throughout the vitreous and delivery to retinal cells. Moreover, a hydrogel implant was developed to act as a depot for the hybrid NPs to better control and slow their release. These results are a first step to improve the treatment of retinal diseases by protecting and transporting the therapeutic treatment across the vitreous and to improve treatment options by creating a depot system for long-term treatments. [ABSTRACT FROM AUTHOR]

Published
2023
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14. Tween® Preserves Enzyme Activity and Stability in PLGA Nanoparticles

Author

Duskey, Jason Thomas, primary, Ottonelli, Ilaria, additional, Rinaldi, Arianna, additional, Parmeggiani, Irene, additional, Zambelli, Barbara, additional, Wang, Leon Z., additional, Prud’homme, Robert K., additional, Vandelli, Maria Angela, additional, Tosi, Giovanni, additional, and Ruozi, Barbara, additional

Published
2021
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16. Microfluidic Technology for the Production of Hybrid Nanomedicines

Author

Ottonelli, Ilaria, primary, Duskey, Jason Thomas, additional, Rinaldi, Arianna, additional, Grazioli, Maria Vittoria, additional, Parmeggiani, Irene, additional, Vandelli, Maria Angela, additional, Wang, Leon Z., additional, Prud’homme, Robert K., additional, Tosi, Giovanni, additional, and Ruozi, Barbara, additional

Published
2021
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18. Microfluidic technology for the production of hybrid nanomedicines

Author

Ottonelli, Ilaria, Duskey, Jason Thomas, Rinaldi, Arianna, Grazioli, Maria Vittoria, Parmeggiani, Irene, Vandelli, Maria Angela, Wang, Leon Z., Prud’homme, Robert K., Tosi, Giovanni, and Ruozi, Barbara

Subjects
hybrid nanoparticles, nanoprecipitation, RS1-441, Pharmacy and materia medica, Nanomedicine, Microfluidics, microfluidics, Hybrid nanoparticles, Nanoprecipitation, nanomedicine, Article
Abstract

Microfluidic technologies have recently been applied as innovative methods for the production of a variety of nanomedicines (NMeds), demonstrating their potential on a global scale. The capacity to precisely control variables, such as the flow rate ratio, temperature, total flow rate, etc., allows for greater tunability of the NMed systems that are more standardized and automated than the ones obtained by well-known benchtop protocols. However, it is a crucial aspect to be able to obtain NMeds with the same characteristics of the previously optimized ones. In this study, we focused on the transfer of a production protocol for hybrid NMeds (H-NMeds) consisting of PLGA, Cholesterol, and Pluronic® F68 from a benchtop nanoprecipitation method to a microfluidic device. For this aim, we modified parameters such as the flow rate ratio, the concentration of core materials in the organic phase, and the ratio between PLGA and Cholesterol in the feeding organic phase. Outputs analysed were the chemico–physical properties, such as size, PDI, and surface charge, the composition in terms of %Cholesterol and residual %Pluronic® F68, their stability to lyophilization, and the morphology via atomic force and electron microscopy. On the basis of the results, even if microfluidic technology is one of the unique procedures to obtain industrial production of NMeds, we demonstrated that the translation from a benchtop method to a microfluidic one is not a simple transfer of already established parameters, with several variables to be taken into account and to be optimized.

Published
2021

22. Steering the Clinical Translation of Delivery Systems for Drugs and Health Products

Author

Curcio, Claudia, Corsaro, Roberta, Bonaccorso, Angela, Musumeci, Teresa, Ruozi, Barbara, and Pignatello, Rosario

Subjects
Computer science, Model prediction, lcsh:RS1-441, Pharmaceutical Science, Clinical settings, 02 engineering and technology, Meeting Report, medical devices, lcsh:Pharmacy and materia medica, 03 medical and health sciences, Controlled delivery, 030304 developmental biology, nutraceuticals, 0303 health sciences, clinical trials, Health management system, Translational medicine, bioinformatics, 021001 nanoscience & nanotechnology, Bench to bedside, Clinical trial, Drug development, Risk analysis (engineering), drug delivery, 0210 nano-technology, controlled release
Abstract

Besides the feasibility for industrial scale-up, accelerating the translation from bench to bedside of new technological strategies for controlled delivery and targeting of drugs and other actives relevant for health management, such as medical devices and nutraceuticals, would benefit from an even earlier evaluation in pre-clinical models and clinical settings. At the same time, translational medicine also performs in the opposite direction, incorporating clinical needs and observations into scientific hypotheses and innovative technological proposals. With these aims, the sessions proposed for the 2019 CRS Italy Chapter Workshop will introduce the experience of Italian and worldwide researchers on how to foster the actual work in controlled release and drug delivery towards a reliable pre-clinical and clinical assessment.

Published
2020

23. Investigating Novel Syntheses of a Series of Unique Hybrid PLGA-Chitosan Polymers for Potential Therapeutic Delivery Applications

Author

Duskey, Jason Thomas, Baraldi, Cecilia, Gamberini, Maria Cristina, Ottonelli, Ilaria, Da Ros, Federica, Tosi, Giovanni, Forni, Flavio, Vandelli, Maria Angela, and Ruozi, Barbara

Subjects
lcsh:QD241-441, FT-IR, lcsh:Organic chemistry, PLGA, chitosan, hybrid polymers, chitosan-PLGA polymer, NMR, DSC, technology, industry, and agriculture, Article
Abstract

Discovering new materials to aid in the therapeutic delivery of drugs is in high demand. PLGA, a FDA approved polymer, is well known in the literature to form films or nanoparticles that can load, protect, and deliver drug molecules; however, its incompatibility with certain drugs (due to hydrophilicity or charge repulsion interactions) limits its use. Combining PLGA or other polymers such as polycaprolactone with other safe and positively-charged molecules, such as chitosan, has been sought after to make hybrid systems that are more flexible in terms of loading ability, but often the reactions for polymer coupling use harsh conditions, films, unpurified products, or create a single unoptimized product. In this work, we aimed to investigate possible innovative improvements regarding two synthetic procedures. Two methods were attempted and analytically compared using nuclear magnetic resonance (NMR), fourier-transform infrared spectroscopy (FT-IR), and dynamic scanning calorimetry (DSC) to furnish pure, homogenous, and tunable PLGA-chitosan hybrid polymers. These were fully characterized by analytical methods. A series of hybrids was produced that could be used to increase the suitability of PLGA with previously non-compatible drug molecules.

Published
2020

26. Synthesis, Characterization, and In Vitro Studies of an Reactive Oxygen Species (ROS)-Responsive Methoxy Polyethylene Glycol-Thioketal-Melphalan Prodrug for Glioblastoma Treatment

Author

Oddone, Natalia, primary, Boury, Frank, additional, Garcion, Emmanuel, additional, Grabrucker, Andreas M., additional, Martinez, M. Carmen, additional, Da Ros, Federica, additional, Janaszewska, Anna, additional, Forni, Flavio, additional, Vandelli, Maria Angela, additional, Tosi, Giovanni, additional, Ruozi, Barbara, additional, and Duskey, Jason T., additional

Published
2020
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29. PLGA-PEG-ANG-2 Nanoparticles for Blood–Brain Barrier Crossing: Proof-of-Concept Study

Author

Hoyos-Ceballos, Gina P., primary, Ruozi, Barbara, additional, Ottonelli, Ilaria, additional, Da Ros, Federica, additional, Vandelli, Maria Angela, additional, Forni, Flavio, additional, Daini, Eleonora, additional, Vilella, Antonietta, additional, Zoli, Michele, additional, Tosi, Giovanni, additional, Duskey, Jason T., additional, and López-Osorio, Betty L., additional

Published
2020
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30. In vitro treatment of congenital disorder of glycosylation type Ia using PLGA nanoparticles loaded with GDP‑Man

Author

Bortot, Barbara, primary, De Martino, Eleonora, additional, Tesser, Alessandra, additional, Ura, Blendi, additional, Ruozi, Barbara, additional, Aloisio, Michelangelo, additional, Biffi, Stefania, additional, Addobbati, Riccardo, additional, Tosi, Giovanni, additional, Dolcetta, Diego, additional, and Severini, Giovanni, additional

Published
2019
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31. Targeting Brain Disease in MPSII: Preclinical Evaluation of IDS-Loaded PLGA Nanoparticles

Author

Rigon, Laura, primary, Salvalaio, Marika, additional, Pederzoli, Francesca, additional, Legnini, Elisa, additional, Duskey, Jason Thomas, additional, D’Avanzo, Francesca, additional, De Filippis, Concetta, additional, Ruozi, Barbara, additional, Marin, Oriano, additional, Vandelli, Maria Angela, additional, Ottonelli, Ilaria, additional, Scarpa, Maurizio, additional, Tosi, Giovanni, additional, and Tomanin, Rosella, additional

Published
2019
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32. Novel Curcumin loaded nanoparticles engineered for Blood-Brain Barrier crossing and able to disrupt Abeta aggregates

Author

Daniela Belletti, Giovanni Tosi, Antonio Ballestrazzi, Martina Masoni, Johannes Keller, Andreas M. Grabrucker, Ruozi Barbara, Francesca Pederzoli, and Maria Angela Vandelli

Subjects
0301 basic medicine, Amyloid, Curcumin, Stereochemistry, Pharmaceutical Science, 02 engineering and technology, Blood–brain barrier, Alzheimer's disease, BBB targeting nanoparticles, Nanotechnology, Synapse, 3003, 03 medical and health sciences, chemistry.chemical_compound, Alzheimer Disease, In vivo, Extracellular, medicine, Humans, Amyloid beta-Peptides, technology, industry, and agriculture, Biological Transport, 021001 nanoscience & nanotechnology, In vitro, PLGA, 030104 developmental biology, medicine.anatomical_structure, chemistry, Blood-Brain Barrier, Drug delivery, Biophysics, Nanoparticles, 0210 nano-technology
Abstract

The formation of extracellular aggregates built up by deposits of β-amyloid (Aβ) is a hallmark of Alzheimer's disease (AD). Curcumin has been reported to display anti-amyloidogenic activity, not only by inhibiting the formation of new Aβ aggregates, but also by disaggregating existing ones. However, the uptake of Curcumin into the brain is severely restricted by its low ability to cross the blood-brain barrier (BBB). Therefore, novel strategies for a targeted delivery of Curcumin into the brain are highly desired. Here, we encapsulated Curcumin as active ingredient in PLGA (polylactide-co-glycolic-acid) nanoparticles (NPs), modified with g7 ligand for BBB crossing. We performed in depth analyses of possible toxicity of these NPs, uptake, and, foremost, their ability to influence Aβ pathology in vitro using primary hippocampal cell cultures. Our results show no apparent toxicity of the formulated NPs, but a significant decrease of Aβ aggregates in response to Curcumin loaded NPs. We thus conclude that brain delivery of Curcumin using BBB crossing NPs is a promising future approach in the treatment of AD.

Published
2017

34. Antineoplastic effects of liposomal siRNA treatment targeting BLIMP1/PRDM1 in primary effusion lymphoma

Author

Riva, Giovanni, Lagreca, Ivana, Mattiolo, Adriana, Belletti, Daniela, Lignitto, Laura, Barozzi, Patrizia, Ruozi, Barbara, Vallerini, Daniela, Quadrelli, Chiara, Corradini, Giorgia, Forghieri, Fabio, Marasca, Roberto, Narni, Franco, Tosi, Giovanni, Forni, Flavio, Vandelli, Maria Angela, Amadori, Alberto, Chieco Bianchi, Luigi, Potenza, Leonardo, Calabro', Maria Luisa, and Luppi, Mario

Subjects
liposomes, BLIMP1/PRDM1, PEL, RNAi, siRNA
Published
2015

35. Targeted Polymeric Nanoparticles for Brain Delivery of High Molecular Weight Molecules in Lysosomal Storage Disorders

Author

Salvalaio, Marika, primary, Rigon, Laura, additional, Belletti, Daniela, additional, D’Avanzo, Francesca, additional, Pederzoli, Francesca, additional, Ruozi, Barbara, additional, Marin, Oriano, additional, Vandelli, Maria Angela, additional, Forni, Flavio, additional, Scarpa, Maurizio, additional, Tomanin, Rosella, additional, and Tosi, Giovanni, additional

Published
2016
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37. Cholesterol‐loaded nanoparticles ameliorate synaptic and cognitive function in H untington's disease mice

Author

Valenza, Marta, primary, Chen, Jane Y, additional, Di Paolo, Eleonora, additional, Ruozi, Barbara, additional, Belletti, Daniela, additional, Ferrari Bardile, Costanza, additional, Leoni, Valerio, additional, Caccia, Claudio, additional, Brilli, Elisa, additional, Di Donato, Stefano, additional, Boido, Marina M, additional, Vercelli, Alessandro, additional, Vandelli, Maria A, additional, Forni, Flavio, additional, Cepeda, Carlos, additional, Levine, Michael S, additional, Tosi, Giovanni, additional, and Cattaneo, Elena, additional

Published
2015
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