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2. Pulmonary Delivery of Nucleic Acids

Author

Conte, Gemma, d’Angelo, Ivana, Müller, Joschka, Winkeljann, Benjamin, Carneiro, Simone, Merkel, Olivia M., Ungaro, Francesca, Salomon, Claudio, Series Editor, Zavod, Robin, Founding Editor, Lam, Jenny, editor, and Kwok, Philip Chi Lip, editor

Published
2023
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14. Boosting lung accumulation of gallium with inhalable nano-embedded microparticles for the treatment of bacterial pneumonia

Author

Costabile, Gabriella, primary, Mitidieri, Emma, additional, Visaggio, Daniela, additional, Provenzano, Romina, additional, Miro, Agnese, additional, Quaglia, Fabiana, additional, d'Angelo, Ivana, additional, Frangipani, Emanuela, additional, Sorrentino, Raffaella, additional, Visca, Paolo, additional, d'Emmanuele di Villa Bianca, Roberta, additional, and Ungaro, Francesca, additional

Published
2022
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16. Pulmonary Safety Profile of Esc Peptides and Esc-Peptide-Loaded Poly(lactide-co-glycolide) Nanoparticles: A Promising Therapeutic Approach for Local Treatment of Lung Infectious Diseases

Author

Cappiello, Floriana, primary, Casciaro, Bruno, additional, Loffredo, Maria Rosa, additional, Puglisi, Elena, additional, Lin, Qiao, additional, Yang, Dandan, additional, Conte, Gemma, additional, d’Angelo, Ivana, additional, Ungaro, Francesca, additional, Ferrera, Loretta, additional, Barbieri, Raffaella, additional, Cresti, Laura, additional, Pini, Alessandro, additional, Di, Yuanpu Peter, additional, and Mangoni, Maria Luisa, additional

Published
2022
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22. Hybrid Lipid/Polymer Nanoparticles to Tackle the Cystic Fibrosis Mucus Barrier in siRNA Delivery to the Lungs: Does PEGylation Make the Difference?

Author

Conte, Gemma, primary, Costabile, Gabriella, additional, Baldassi, Domizia, additional, Rondelli, Valeria, additional, Bassi, Rosaria, additional, Colombo, Diego, additional, Linardos, Giulia, additional, Fiscarelli, Ersilia V., additional, Sorrentino, Raffaella, additional, Miro, Agnese, additional, Quaglia, Fabiana, additional, Brocca, Paola, additional, d’Angelo, Ivana, additional, Merkel, Olivia M., additional, and Ungaro, Francesca, additional

Published
2022
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23. Alcohol-Based Hand Sanitizers: Does Gelling Agent Really Matter?

Author

d’Angelo, Ivana, primary, Provenzano, Romina, additional, Florio, Ettore, additional, Pagliuca, Chiara, additional, Mantova, Giuseppe, additional, Scaglione, Elena, additional, Vitiello, Mariateresa, additional, Colicchio, Roberta, additional, Salvatore, Paola, additional, Ungaro, Francesca, additional, Quaglia, Fabiana, additional, and Miro, Agnese, additional

Published
2022
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24. Inhalable Polymeric Nanoparticles for Pulmonary Delivery of Antimicrobial Peptide SET-M33: Antibacterial Activity and Toxicity In Vitro and In Vivo.

Author

Cresti, Laura, Conte, Gemma, Cappello, Giovanni, Brunetti, Jlenia, Falciani, Chiara, Bracci, Luisa, Quaglia, Fabiana, Ungaro, Francesca, d'Angelo, Ivana, and Pini, Alessandro

Subjects
ANTIMICROBIAL peptides, ANTIBACTERIAL agents, ACUTE toxicity testing, PEPTIDES, LUNG development
Abstract

Development of inhalable formulations for delivering peptides to the conductive airways and shielding their interactions with airway barriers, thus enhancing peptide/bacteria interactions, is an important part of peptide-based drug development for lung applications. Here, we report the construction of a biocompatible nanosystem where the antimicrobial peptide SET-M33 is encapsulated within polymeric nanoparticles of poly(lactide-co-glycolide) (PLGA) conjugated with polyethylene glycol (PEG). This system was conceived for better delivery of the peptide to the lungs by aerosol. The encapsulated peptide showed prolonged antibacterial activity, due to its controlled release, and much lower toxicity than the free molecule. The peptide-based nanosystem killed Pseudomonas aeruginosa in planktonic and sessile forms in a dose-dependent manner, remaining active up to 72 h after application. The encapsulated peptide showed no cytotoxicity when incubated with human bronchial epithelial cells from healthy individuals and from cystic fibrosis patients, unlike the free peptide, which showed an EC50 of about 22 µM. In vivo acute toxicity studies in experimental animals showed that the peptide nanosystem did not cause any appreciable side effects, and confirmed its ability to mitigate the toxic and lethal effects of free SET-M33. [ABSTRACT FROM AUTHOR]

Published
2023
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30. Assisting PNA Transport Through Cystic Fibrosis Human Airway Epithelia With Biodegradable Hybrid Lipid-Polymer Nanoparticles

Author

Comegna, Marika, primary, Conte, Gemma, additional, Falanga, Andrea, additional, Marzano, Maria, additional, Cernera, Gustavo, additional, Lullo, Antonella Di, additional, Amato, Felice, additional, Borbone, Nicola, additional, D'Errico, Stefano, additional, Ungaro, Francesca, additional, d'Angelo, Ivana, additional, Oliviero, Giorgia, additional, and Castaldo, Giuseppe, additional

Published
2020
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31. Poly(lactide-co-glycolide) Nanoparticles for Prolonged Therapeutic Efficacy of Esculentin-1a-Derived Antimicrobial Peptides against Pseudomonas aeruginosa Lung Infection: in Vitro and in Vivo Studies

Author

Casciaro, Bruno, primary, d’Angelo, Ivana, additional, Zhang, Xiaoping, additional, Loffredo, Maria Rosa, additional, Conte, Gemma, additional, Cappiello, Floriana, additional, Quaglia, Fabiana, additional, Di, Yuan-Pu Peter, additional, Ungaro, Francesca, additional, and Mangoni, Maria Luisa, additional

Published
2019
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32. Improved delivery of angiogenesis inhibitors from PLGA:poloxamer blend micro- and nanoparticles

Author

D'ANGELO, Ivana, Parajó, Yb, Y. B, Horvth, Ac, A. C, Kéri, Gc, G. C, Rotonda, La, Mia, M. I. A, Alonso, D'Angelo, Ivana, Parajó, Yb, Y. B, Horvth, Ac, A. C, Kéri, Gc, G. C, Rotonda, La, Mia, M. I. A, and Alonso

Subjects
Materials science, Pharmaceutical Science, Nanoparticle, Excipient, Angiogenesis Inhibitors, Angiogenesis inhibitor, Bioengineering, Poloxamer, chemistry.chemical_compound, Colloid and Surface Chemistry, Polylactic Acid-Polyglycolic Acid Copolymer, Polymer chemistry, medicine, Lactic Acid, Particle Size, Physical and Theoretical Chemistry, Microparticle, Organic Chemistry, technology, industry, and agriculture, PLGA, Controlled release, Kinetics, chemistry, Delayed-Action Preparations, Emulsion, Nanoparticles, Particle size, Polyglycolic Acid, medicine.drug, Biomedical engineering
Abstract

Clinical studies have demonstrated the efficacy of new strategies in cancer therapy, such as chemotherapy and radiotherapy, associated to the administration of tumour vascularization inhibitors. A critical limitation for the clinical application of angiogenesis inhibitors relies in their instability in biological environment and high-dose requirements. This work has attempted to overcome this limitation by designing an adequate delivery vehicle consisting of PLGA:poloxamer blend micro- and nanoparticles. The potential of this delivery system was investigated for a new synthetic angiogenesis inhibitor named polyaminoacid JS-2892b. PLGA:poloxamer (ratio 10 : 1) blend microparticles were prepared by the oil-in-oil emulsion technique, while PLGA:poloxamer (ratio 1 : 1) blend nanoparticles were obtained by a modified solvent diffusion technique. The results showed that, by adjusting the formulation conditions, it was possible to efficiently encapsulate the polyaminoacid JS-2892b within PLGA:poloxamer micro- (particle size of 20 μm and encapsulation efficiency higher than 90%) and nanoparticles (particle size of less than 280 nm and encapsulation efficiency of 52%). In addition, the delivery of the polyaminoacid JS-2892b from the particles could be controlled, without altering its stability, for extended periods of time (from a few days to over a month). The release of the encapsulated compound was significantly affected by the particle size and the way the drug is dispersed into the polymeric matrix. Therefore, this study provides information about the formulation conditions and potential of biodegradable particles for the controlled release of polyaminoacid JS-2892b. © 2010 Informa UK Ltd.

Published
2010
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33. Hybrid Lipid/Polymer Nanoparticles for Pulmonary Delivery of siRNA: Development and Fate Upon In Vitro Deposition on the Human Epithelial Airway Barrier

Author

d'Angelo, Ivana, primary, Costabile, Gabriella, additional, Durantie, Estelle, additional, Brocca, Paola, additional, Rondelli, Valeria, additional, Russo, Annapina, additional, Russo, Giulia, additional, Miro, Agnese, additional, Quaglia, Fabiana, additional, Petri-Fink, Alke, additional, Rothen-Rutishauser, Barbara, additional, and Ungaro, Francesca, additional

Published
2018
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36. Large Porous Particles for Sustained Release of a Decoy Oligonucelotide and Poly(ethylenimine): Potential for Combined Therapy of Chronic Pseudomonas aeruginosa Lung Infections

Author

d’Angelo, Ivana, primary, Perfetto, Brunella, additional, Costabile, Gabriella, additional, Ambrosini, Veronica, additional, Caputo, Pina, additional, Miro, Agnese, additional, d’Emmanuele di Villa Bianca, Roberta, additional, Sorrentino, Raffaella, additional, Donnarumma, Giovanna, additional, Quaglia, Fabiana, additional, and Ungaro, Francesca, additional

Published
2016
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37. Hybrid Lipid/Polymer Nanoparticles for Pulmonary Delivery of siRNA: Development and Fate Upon <italic>In Vitro</italic> Deposition on the Human Epithelial Airway Barrier.

Author

d'Angelo, Ivana, Costabile, Gabriella, Durantie, Estelle, Brocca, Paola, Rondelli, Valeria, Russo, Annapina, Russo, Giulia, Miro, Agnese, Quaglia, Fabiana, Petri-Fink, Alke, Rothen-Rutishauser, Barbara, and Ungaro, Francesca

Subjects
*NANOPARTICLES, *SMALL interfering RNA, *SODIUM channels, *HYDRODYNAMICS, *SMALL-angle X-ray scattering
Abstract

Background: Nowadays, the downregulation of genes involved in the pathogenesis of severe lung diseases through local siRNA delivery appears an interesting therapeutic approach. In this study, we propose novel hybrid lipid-polymer nanoparticles (hNPs) consisting of poly(lactic-co-glycolic) acid (PLGA) and dipalmitoyl phosphatidylcholine (DPPC) as siRNA inhalation system. Methods: A panel of DPPC/PLGA hNPs was prepared by emulsion/solvent diffusion and fully characterized. A combination of model siRNAs against the sodium transepithelial channel (ENaC) was entrapped in optimized hNPs comprising or not poly(ethylenimine) (PEI) as third component. siRNA-loaded hNPs were characterized for encapsulation efficiency, release kinetics, aerodynamic properties, and stability in artificial mucus (AM). The fate and cytotoxicity of hNPs upon aerosolization on a triple cell co-culture model (TCCC) mimicking human epithelial airway barrier were assessed. Finally, the effect of siRNA-loaded hNPs on ENaC protein expression at 72 hours was evaluated in A549 cells. Results: Optimized muco-inert hNPs encapsulating model siRNA with high efficiency were produced. The developed hNPs displayed a hydrodynamic diameter of ∼150 nm, a low polydispersity index, a negative ζ potential close to −25 mV, and a peculiar triphasic siRNA release lasting for 5 days, which slowed down in the presence of PEI. siRNA formulations showed optimal in vitro aerosol performance after delivery with a vibrating mesh nebulizer. Furthermore, small-angle X-ray scattering analyses highlighted an excellent stability upon incubation with AM, confirming the potential of hNPs for direct aerosolization on mucus-lined airways. Studies in TCCC confirmed that fluorescent hNPs are internalized inside airway epithelial cells and do not exert any cytotoxic or acute proinflammatory effect. Finally, a prolonged inhibition of ENaC protein expression was observed in A549 cells upon treatment with siRNA-loaded hNPs. Conclusions: Results demonstrate the great potential of hNPs as carriers for pulmonary delivery of siRNA, prompting toward investigation of their therapeutic effectiveness in severe lung diseases. [ABSTRACT FROM AUTHOR]

Published
2018
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38. Poly(lactide-co-glycolide) Nanoparticles for Prolonged Therapeutic Efficacy of Esculentin-1a-Derived Antimicrobial Peptides against Pseudomonas aeruginosaLung Infection: in Vitro and in Vivo Studies

Author

Casciaro, Bruno, d’Angelo, Ivana, Zhang, Xiaoping, Loffredo, Maria Rosa, Conte, Gemma, Cappiello, Floriana, Quaglia, Fabiana, Di, Yuan-Pu Peter, Ungaro, Francesca, and Mangoni, Maria Luisa

Abstract

Due to their excellent in vitro activity against multidrug resistant bacteria, antimicrobial peptides (AMPs) hold promise for treatment of Pseudomonas aeruginosalung infections in cystic fibrosis (CF) sufferers. In this work, poly(lactide-co-glycolide) (PLGA) nanoparticles for lung delivery of AMPs deriving from the frog-skin esculentin-1a, namely, Esc(1-21) and Esc(1-21)-1c (Esc peptides), were successfully developed. Improved peptide transport through artificial CF mucus and simulated bacterial extracellular matrix was achieved in vitro. The formulations were effectively delivered through a liquid jet nebulizer already available to patients. Notably, Esc peptide-loaded nanoparticles displayed an improved efficacy in inhibiting P. aeruginosagrowth in vitro and in vivo in the long term. A single intratracheal administration of Esc peptide-loaded nanoparticles in a mouse model of P. aeruginosalung infection resulted in a 3-log reduction of pulmonary bacterial burden up to 36 h. Overall, results unravel the potential of PLGA nanoparticles as a reliable delivery system of AMPs to lungs.

Published
2019
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40. Toward Repositioning Niclosamide for Antivirulence Therapy of Pseudomonas aeruginosa Lung Infections: Development of Inhalable Formulations through Nanosuspension Technology

Author

Costabile, Gabriella, primary, d’Angelo, Ivana, additional, Rampioni, Giordano, additional, Bondì, Roslen, additional, Pompili, Barbara, additional, Ascenzioni, Fiorentina, additional, Mitidieri, Emma, additional, d’Emmanuele di Villa Bianca, Roberta, additional, Sorrentino, Raffaella, additional, Miro, Agnese, additional, Quaglia, Fabiana, additional, Imperi, Francesco, additional, Leoni, Livia, additional, and Ungaro, Francesca, additional

Published
2015
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50. Transmucosal delivery of the medical Cannabisoil via a nanoemulsion formulation

Author

d’Angelo, Ivana, Provenzano, Romina, Florio, Ettore, Lombardi, Annunziata, Trama, Ugo, Ungaro, Francesca, Quaglia, Fabiana, and Miro, Agnese

Abstract

Nowadays,oral oil extracts of Cannabisrepresent the most relevant galenic plant-derived formulations employed in clinics. Nevertheless, the low and variable Δ9-tetrahydrocannabinol (THC) oral bioavailability due to hepatic first-pass metabolism and low solubility in biological fluids makes Cannabispharmacological response highly unpredictable. In this scenario, new formulation strategies appear crucial to improve cannabinoids bioavailability and stability, administration comfort and patient compliance. Here, we present a nanoemulsion (NE) for the buccal administration of olive oil extract from a Cannabis sativaL. variety (Bedrocan®). A preliminary study was carried out on olive oil-based NE to identify the optimal formulation conditions to achieve a stable system. The Bedrocan®-loaded NE were then prepared and characterized for size, polydispersity index, stability upon delivery by the common buccal nebulizers.

Published
2023
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