Laura Tiozzo Fasiolo

Istituto Oncologico Veneto

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Gaia Colombo

University of Ferrara

Fabio Sonvico

University of Parma

Fabrizio Bortolotti

University of Ferrara

Michele Dario Manniello

University of Salerno

Paola Russo

University of Salerno

Adriana Raffin Pohlmann

Universidade Federal do Rio Grande do Sul

Alessio Fabozzi

University of Campania "Luigi Vanvitelli"

Valentina Salizzato

Istituto Oncologico Veneto

Magno da Silva Marques

Universidade Federal do Rio Grande

Georgia Valsami

National and Kapodistrian University of Athens

Cooperative Institutions

Istituto Oncologico Veneto

Istituti di Ricovero e Cura a Carattere Scientifico

University of Padua

University of Parma

University of Ferrara

University of Florence

Universidade Federal do Rio Grande do Sul

University of Milan

National and Kapodistrian University of Athens

Regione del Veneto

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Flurbiprofen sodium microparticles and soft pellets for nose-to-brain delivery: Serum and brain levels in rats after nasal insufflation

International Journal of Pharmaceutics (2021)

Laura Tiozzo Fasiolo Michele Dario Manniello Sabrina Banella Laura Napoli Fabrizio Bortolotti

Flurbiprofen

10.1016/j.ijpharm.2021.120827

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Citations (18)

Chitosan-Coated Nanoparticles: Effect of Chitosan Molecular Weight on Nasal Transmucosal Delivery

Pharmaceutics (2019)

Franciele Aline Bruinsmann Stefania Pigana Tanira Alessandra Silveira Aguirre Gabriele Dadalt Souto Gabriela Garrastazu Pereira

Drug delivery to the brain represents a challenge, especially in the therapy of central nervous system malignancies. Simvastatin (SVT), as with other statins, has shown potential anticancer properties that are difficult to exploit in the central nervous system (CNS). In the present work the physico–chemical, mucoadhesive, and permeability-enhancing properties of simvastatin-loaded poly-ε-caprolactone nanocapsules coated with chitosan for nose-to-brain administration were investigated. Lipid-core nanocapsules coated with chitosan (LNCchit) of different molecular weight (MW) were prepared by a novel one-pot technique, and characterized for particle size, surface charge, particle number density, morphology, drug encapsulation efficiency, interaction between surface nanocapsules with mucin, drug release, and permeability across two nasal mucosa models. Results show that all formulations presented adequate particle sizes (below 220 nm), positive surface charge, narrow droplet size distribution (PDI < 0.2), and high encapsulation efficiency. Nanocapsules presented controlled drug release and mucoadhesive properties that are dependent on the MW of the coating chitosan. The results of permeation across the RPMI 2650 human nasal cell line evidenced that LNCchit increased the permeation of SVT. In particular, the amount of SVT that permeated after 4 hr for nanocapsules coated with low-MW chitosan, high-MW chitosan, and control SVT was 13.9 ± 0.8 μg, 9.2 ± 1.2 µg, and 1.4 ± 0.2 µg, respectively. These results were confirmed by SVT ex vivo permeation across rabbit nasal mucosa. This study highlighted the suitability of LNCchit as a promising strategy for the administration of simvastatin for a nose-to-brain approach for the therapy of brain tumors.

Nanocapsules

Mucoadhesion

Surface charge

Nanocarriers

10.3390/pharmaceutics11020086

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Citations (107)

Anti-inflammatory flurbiprofen nasal powders for nose-to-brain delivery in Alzheimer’s disease

Journal of drug targeting (2019)

Laura Tiozzo Fasiolo Michele Dario Manniello Fabrizio Bortolotti Francesca Buttini Alessandra Rossi

Neuroinflammation occurs in the early stages of Alzheimer's disease (AD). Thus, anti-inflammatory drugs in this asymptomatic initial phase could slow down AD progression, provided they enter the brain. Direct nose-to-brain drug transport occurs along olfactory or trigeminal nerves, bypassing the blood-brain barrier. Nasal administration may enable the drug to access the brain. Here, flurbiprofen powders for nose-to-brain drug transport in early AD-related neuroinflammation were studied. Their target product profile contemplates drug powder deposition in the nasal cavity, prompt dissolution in the mucosal fluid and attainment of saturation concentration to maximise diffusion in the tissue. Aiming to increase drug disposition into brain, poorly soluble flurbiprofen requires the construction of nasal powder microparticles actively deposited in nose for prompt drug release. Two groups of powders were formulated, composed of flurbiprofen acid or flurbiprofen sodium salt. Two spray dryer apparatuses, differing for spray and drying mechanisms, and particle collection, were applied to impact on the characteristics of the microparticulate powders. Flurbiprofen sodium nasal powders disclosed prompt dissolution and fast ex vivo transport across rabbit nasal mucosa, superior to the acid form, in particular when the powder was prepared using the Nano B-90 spray dryer at the lowest drying air temperature.

Flurbiprofen

Nasal spray

10.1080/1061186x.2019.1574300

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Citations (26)

P.6.c.003 Changes of the 5-HT1B receptors protein level after chronic amphetamine self-administration and its withdrawal in designated structures of rat brain

European Neuropsychopharmacology (2015)

Joanna Miszkiel Grzegorz Kazek Laura Tiozzo Fasiolo Joanna Jastrzębska

10.1016/s0924-977x(15)30861-0

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Citations (0)

Chitosan-Coated Nanoparticles: Effect of Chitosan Molecular Weight on Nasal Transmucosal Delivery

Franciele Aline Bruinsmann Stefania Pigana Tanira Alessandra Silveira Aguirre Gabriele Dadalt Souto Gabriele Garrastazu Pereira

Drug delivery to the brain represents a challenge especially in the therapy of central nervous system malignancies. Simvastatin (SVT), as other statins, has shown potential anticancer properties that are difficult to exploit in the CNS. In the present work the physico-chemical, mucoadhesive and permeability enhancing properties of simvastatin-loaded poly-ε-caprolactone nanocapsules coated with chitosan for nose-to-brain administration were investigated. Lipid-core nanocapsules coated with different molecular weight (MW) chitosans (LNCchit) prepared by a novel one-pot technique were characterized for particle size, surface charge, particle number density, morphology, drug encapsulation efficiency, interaction between surface nanocapsules with mucin, drug release and permeability across two nasal mucosa models. Results show that all formulations present adequate particle size (below 220 nm), positive surface charge, narrow droplet size distribution (PDI<0.2) and high encapsulation efficiency. Nanocapsules presented controlled drug release and mucoadhesive properties dependent on the MW of the coating chitosan. The results of permeation across RPMI 2650 human nasal cell line evidenced that LNCchit increased the permeation of SVT. In particular, the amount of SVT permeated after 4h for nanocapsules coated with low MW chitosan, high MW chitosan and control SVT was 13.91 ± 0.78 µg, 9.15 ± 1.23 µg and 1.42 ± 0.21 µg respectively. These results were confirmed by the SVT ex vivo permeation across rabbit nasal mucosa. This study highlighted the suitability of LNCchit as promising strategy for the administration of simvastatin for a nose-to-brain approach for the therapy of brain tumors.

Nanocapsules

Mucoadhesion

Surface charge

Nanocarriers

10.20944/preprints201902.0034.v1

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Citations (30)

Chitosan coated human serum albumin nanoparticles: A promising strategy for nose-to-brain drug delivery

International Journal of Biological Macromolecules (2019)

Vieri Piazzini Elisa Landucci Mario D’Ambrosio Laura Tiozzo Fasiolo Lorenzo Cinci

Mucoadhesion

Human serum albumin

10.1016/j.ijbiomac.2019.02.005

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Citations (102)

Circulating cytokines as predictors of response to immune checkpoint inhibitors (ICIs) in patients (pts) with melanoma (Mel) and non–small cell lung cancer (NSCLC).

Journal of Clinical Oncology (2022)

Giulia Pasello Aline S.C. Fabricio Paola Del Bianco Adolfo Favaretto Valentina Salizzato

2549 Background: ICIs lead to durable response and a significant survival improvement in a limited number of advanced stage Mel and NSCLC pts. The identification of predictive circulating biomarkers could be a promising tool to optimize pts’ selection and outcome for ICIs treatment. Methods: This is a prospective real-world study enrolling advanced stage Mel and NSCLC pts referred to four Italian Centers and treated with ICIs. The primary endpoint is to verify the presence of an association between circulating cytokines (IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, TNFα, GM-CSF) and disease control rate (DCR), progression free survival (PFS) and overall survival (OS). Pts undergo a blood collection, before every cycle for 6 cycles (T1-T6) and at tumor assessment till disease progression (PD) or for 2 years. Biomarker levels were assessed by Luminex xMAP based technology using R&D High Sensitivity kits. Each marker was categorized according to high and low levels by maximizing its discriminative ability, and the association with the outcome was tested in univariate and multiple analyses. Results: We report preliminary results on the T1-T2 blood samples from the first 78 enrolled pts (32 females/46 males; 43 Mel/35 NSCLC; median age 69 years). Serum IL-6, IL-8 and IL-10 were significantly higher at T1 and T2 in pts with PD (Kruskal-Wallis test). The median relative increase (RI) of IL-8 was 32% and 2% in pts with PD and disease control (DC), respectively (p = 0.0001). At multiple logistic analysis, IL-6 and IL-8 at T2 and the RI of IL-8 were independent factors predicting the probability of DC, with an overall accuracy of 83.8%. High levels of IL-6 and IL-8 at T2 were significantly associated with a low probability of DC (OR = 0.13, 95%CI: 0.03-0.52 and OR = 0.09, 95%CI: 0.02-0.37, respectively), and the RI showed a significantly lower probability of DC (OR = 0.14, 95%CI: 0.02-0.58). With a median follow-up of 10.6 months (m), mPFS and mOS were 5.8 m, 95%CI: 2.3-7.4 and 8.3 m, 95%CI: 4.0-13.8 for NSCLC; 6.9 m, 95%CI: 2.8-15.9 and 12.6 m, 95%CI: 4.7-NE for Mel pts, respectively. In the multiple Cox model, elevated IL-6 and IL-8 at T1 (HR = 3.03, 95%CI: 1.55-6.37, HR = 2.86, 95%CI: 1.46-5.63), elevated IL-10 at T2 (HR = 2.86, 95%CI: 1.39-5.94), and a RI of IL-8 (HR = 4.22, 95%CI: 1.85-11.21) remained significantly associated with a worse PFS. Higher levels of IL-6 (HR = 3.85, 95%CI: 1.13-20.0) and IL-8 (HR = 4.29, 95%CI: 1.98-9.83) at T2 and a RI of IL-8 (HR = 3.06, 95%CI: 1.43-6.72) remained significantly associated with a worse OS. Conclusions: High serum levels of IL-8 and IL-6 at T2 of ICI, combined with an increase of IL-8 from baseline, are strong predictors of PD, PFS, OS, in pts with advanced Mel and NSCLC. The role of the other cytokines tested, their time fluctuations and associations with clinical prognostic factors, gender, and immuno-related adverse events will be presented at the meeting.

Clinical endpoint

Univariate analysis

10.1200/jco.2022.40.16_suppl.2549

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Citations (3)

Isotonia e soluzioni tampone

Beatrice Albertini Martha Biondi G. Bonacucina L. Casettari R. Cassano

Source

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Citations (0)

Neurotensin: A role in substance use disorder?

Journal of Psychopharmacology (2016)

Luca Ferraro Laura Tiozzo Fasiolo Sarah Beggiato Andrea Celeste Borelli Lucyna Pomierny-Chamioło

Neurotensin is a tridecapeptide originally identified in extracts of bovine hypothalamus. This peptide has a close anatomical and functional relationship with the mesocorticolimbic and nigrostriatal dopamine system. Neural circuits containing neurotensin were originally proposed to play a role in the mechanism of action of antipsychotic agents. Additionally, neurotensin-containing pathways were demonstrated to mediate some of the rewarding and/or sensitizing properties of drugs of abuse. This review attempts to contribute to the understanding of the role of neurotensin and its receptors in drug abuse. In particular, we will summarize the potential relevance of neurotensin, its related compounds and neurotensin receptors in substance use disorders, with a focus on the preclinical research.

Neurotensin receptor

10.1177/0269881115622240

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Citations (40)

Cytokine and soluble programmed death-ligand 1 levels in serum and plasma of cancer patients treated with immunotherapy: Preanalytical and analytical considerations

The International Journal of Biological Markers (2024)

Elia Cappelletto Laura Tiozzo Fasiolo Valentina Salizzato Luisa Piccin Alessio Fabozzi

To evaluate cytokine and soluble programmed death ligand-1 (sPD-L1) levels in the serum and plasma of cancer patients treated with immunotherapy, and to test different assays.

Cancer Immunotherapy

10.1177/03936155231226234

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Citations (3)