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Innovative Pharmaceutical and Cosmetic Technology and Nanotechnology Group (i-PHARCOTEC)

Componenti

Fotografia

Settore ERC

LS7_3 - Nanomedicine
LS7_12 - Health care, including care for the ageing population
PE5_6 - New materials: oxides, alloys, composite, organic-inorganic hybrid, nanoparticles
PE5_10 - Colloid chemistry

Attività


Il gruppo i-PHARCOTEC possiede una consolidata esperienza nella progettazione, preparazione e caratterizzazione di formulazioni farmaceutiche innovative costituite da nano e/o microparticelle a matrice polimerica, lipidica e inorganica. In particolare, vengono sviluppate nanoparticelle polimeriche, nanoparticelle solide lipidiche, liposomi, coniugati polimero-farmaco, nanoparticelle a base di ciclodestrine, nanocristalli, sistemi a base di nanovescicole (nanobolle, nanocapsule), nano e microemulsioni per applicazioni farmaceutiche e/o cosmetiche. Inoltre, parte della ricerca è focalizzata allo sviluppo di sistemi direzionati, sfruttando strategie su più fronti.

Tali approcci formulativi sono tutti guidati dal principio attivo:

  • vengono sviluppate strategie formulative in funzione delle caratteristiche chimico-fisiche del farmaco/sostanza funzionale da caricare all'interno dei micro/nanosistemi, tra cui idro/lipofilia, peso molecolare, stabilità chimica e termica;
  • le dimensioni e le proprietà superficiali dei micro/nanosistemi sono ottimizzate al fine di raggiungere il sito bersaglio
  • la struttura composita del micro/nanosistema è progettata per migliorare la solubilità del farmaco e/o per ottenere il suo rilascio prolungato

 

Le attività di ricerca in campo farmaceutico sono focalizzate principalmente sui seguenti argomenti:

  • sviluppo di nanoparticelle lipidiche per il rilascio di farmaci e il direzionamento ai tumori solidi, quali il carcinoma mammario triplo negativo e l'osteosarcoma. Le nanoparticelle sono opportunamente funzionalizzate in base al target selezionato;

 

  •  sviluppo di microemulsioni olio-in-acqua e acqua-in-olio gelificanti in situ per il rilascio corneale di farmaci, la cui viscosità aumenta dopo la somministrazione, sia per la formazione di una struttura liquido-cristallina, sia per gelificazione indotta dalla temperatura corporea;

 

  •  sviluppo di sistemi di rilascio nanocompositi oftalmici (microemulsioni olio-in-acqua e nanoparticelle lipidiche), per la somministrazione intravitreale di farmaci, quali antibiotici, agenti antinfiammatori e anti-VEGF. Una cella di flusso oculare a 3 compartimenti in plexiglas, progettata e sviluppata nel laboratorio Pharcotec, consente la simulazione della farmacocinetica oftalmica;

 

  • formulazione e caratterizzazione di nanobolle polimeriche per la veicolazione di farmaci, gas e materiale genetico;
  • sviluppo di polimeri cationici e nanoparticelle per il rilascio intracellulare di siRNA;
  • preparazione e caratterizzazione di nanosistemi per la somministrazione di farmaci antibiotici o antivirali;
  • formulazione di complessi di inclusione di ciclodestrine o nanoparticelle a base di ciclodestrine (es. nanospugne) per aumentare la solubilità e la biodisponibilità dei farmaci;
  • progettazione di nanosistemi polimerici per il rilascio direzionato di farmaci antitumorali nel sito tumorale;
  • nanovaccini per l'immunoterapia oncologica

 

Attività di ricerca in corso in campo cosmetico:

  • formulazione e caratterizzazione di sistemi colloidali solidi, semisolidi e liquidi destinati all'applicazione cutanea;
  • veicolazione di molecole interessanti in campo dermatologico e cosmetico: antiossidanti naturali; vitamine; filtri UV organici e inorganici; fotosensibilizzatori; altri farmaci per i disturbi della pelle;
  • determinazione di metalli pesanti contenuti in prodotti cosmetici e studio della permeazione cutanea;
  • studio delle alterazioni morfologiche, biochimiche e meccaniche di capelli esposti ad agenti chimici e fisici;
  • sviluppo di formulazioni tricologiche termo- e fotoprotettive e verifica in vitro dell'efficacia.

 

upload_pharcotec_fig.1.jpgSolid lipid nanoparticles

upload_Immagine1.pngIn-situ gelling microemulsions

upload_2.pngOcular 3-compartments flow cell

 

 

 

 

 

 

 

 

 

 

 

 

upload_pig_skin.jpg

upload_hair1.jpg

Principali tecnologie disponibili:

  • liofilizzazione
  • analisi termica (calorimetria a scansione differenziale DSC)
  • determinazione della dimensione e del potenziale Zeta delle particelle mediante Dynamic Light Scattering (DLS)
  • frazionamento in Campo-Flusso (FFF)
  • microscopia ottica
  • misure reologiche
  • studi di permeazione in vitro (membrane sintetiche/pelle/cornea) con celle di Franz
  • studi di fotostabilità (simulatori della luce solare)
  • studi di stabilità di sistemi dispersi
  • valutazione della conducibilità e della tensione superficiale
  • determinazione non invasiva dei parametri fisiologici cutanei (mediante corneometro, sebometro, colorimetro, glossimetro, cutometro, pH-metro cutaneo).

 

 

Figure 3. Sunlight simulatorsimulatori della luce solare

 

upload_cutometer.jpgCutometro


- Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino 

- S.C. Farmacia Ospedaliera A.O. Ordine Mauriziano, Torino

- Istituto di Candiolo - IRCCS, Candiolo 

- Società Prodotti Antibiotici S.p.A

- Dipartimento di Scienza della Salute, Università del Piemonte Orientale, Novara 

- Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale, Novara

- Centro di Riferimento Oncologico (CRO) di Aviano IRCCS, Aviano 

- Neuroengineering and Neuroprosthesis Unit at the Bioengineering Institute. University Miguel Hernández (Spain)

- Department of Pharmaceutical Sciences, School of Health Sciences of Polytechnic Institute of Guarda (Guarda, Portugal)

- Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA) La Plata (Argentina)

- Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel), Prof. Ronit Satchi-Fainaro

- Research Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, University of Lisbon, Lisboa (Portugal), Prof. Helena Florindo

- Advanced Drug Delivery and Biomaterials, Louvain Drug Research Institute, UCLouvain (Belgium)

- Gliomagenesis and Microenvironment, Institute of NeuroPhysiopathology, Aix-Marseille University (France)





To develop innovative and smart nanosystems for drug delivery by exploiting drug-driven formulation approaches.

The i-PHARCOTEC group owns a widespread and established expertise in the design, preparation and characterization of innovative drug formulations by means of nano and/or microparticles, based on polymer, lipid and inorganic matrixes. In particular, polymeric nanoparticles, solid lipid nanoparticles, liposomes, polymer-drug conjugates, cyclodextrin-based nanoparticles, nanocrystals, nanovesicle-based systems (i.e. nanobubbles, nanocapsules), nano and microemulsion are developed for pharmaceutical and/or cosmetic applications. Moreover, such research has also been focused on the development of targeted nanosystems, by using multi-pronged strategies.
Such formulative approaches are all drug-driven;that is:

  1. formulation strategies are developed owing to the physico-chemical features of the drug/functional ingredient to be loaded within the micro/nanosystems, including hydro/lipophilicity, molecular weight, chemical and thermal stability;
  2. size and surface properties of micro/nanosystems are optimized, in order to enable them to deliver their cargo to its specific target site;
  3. micro/nanosystem composite structure is designed in order to enhance the drug solubility and/or to achieve its sustained release.

 

Research activities in pharmaceutical field are mainly focused on the following topics:

  • Formulation and characterization of lipid nanoparticles (solid lipid nanoparticles or nanostructured lipid carriers) for drug delivery and targeting to solid tumor, such as triple negative breast cancer and osteosarcoma. Nanoparticles are suitably decorated on their surface according to the selected target.
  • Formulation and characterization of in-situ gelling microemulsion systems for corneal delivery of drugs.
    Oil-in-water and water-in-oil microemulsions are developed, whose viscosity increases after administration, either by the formation of a liquid-crystalline structure, or by body-temperature-induced jellification. Consequently, the precorneal residence time increases, reducing the frequency of administration of ophthalmic systems.
  • Development of ophthalmic nanocomposite delivery systems (i.e. O/W microemulsion and lipid nanoparticles), for intravitreal administration of drugs, such as antibiotics, anti-inflammatory and anti-VEGF agents. For characterization of these systems an ocular flow cell, is used. The Plexiglas 3-compartment eye flow cell, designed and developed in the Pharcotec lab allows the simulation of ophthalmic pharmacokinetics. It is formed by an anterior and a posterior cavity, mimicking the anterior and the posterior sections of the eye; in addition, the posterior cavity is composed of a central unit, acting as the vitreous cavity, in which it formulations for intravitreal administration can be injected, and of a posterior one, separated by a support for retinal cell cultures.

 

  • Formulation and characterization of polymeric nanobubbles for the delivery of drugs, gases and genetic material.
  • Development of cationic polymers and nanoparticles for the intracellular delivery of siRNA
  • Preparation and characterization of nanosystems for antibiotic or antiviral drug delivery
  • Formulation of cyclodextrin inclusion complexes or cyclodextrin-based nanoparticles (i.e. nanosponges) to increase the solubility and bioavailability of drugs
  • Design of polymeric nanosystems for the targeted delivery of anticancer drugs to the tumor site
  • Nanovaccines for cancer immunotherapy

Research activities in progress in cosmetic field:

  • formulation and characterization of solid, semi-solid and liquid colloidal systems intended for skin application;
  • delivery of interesting molecules in the dermatological and cosmetic fields: natural antioxidants; vitamins; organic and inorganic UV filters; photosensitizers; other medications for skin disorders;
  • determination of heavy metals contained in cosmetic products and skin permeation study;
  • study of the morphological, biochemical and mechanical changes of hair exposed to chemical and physical agents;
  • development of thermo- and photoprotective hair care formulations and in vitro efficacy evaluation.

 

upload_pharcotec_fig.1.jpg

Solid lipid nanoparticles

upload_Immagine1.png

In-situ gelling microemulsions

upload_2.png

Ocular 3-compartments flow cell

 

 

 

 

 

 

 

 

 

 

upload_pig_skin1.jpg

upload_hair2.jpg

 

Main available technologies:

  • Freeze drying
  • Thermal analysis (DSC)
  • Particle size and Zeta potential determination (Dynamic Light Scattering DLS)
  • Multi Flow FFF Separation
  • Optical microscopy
  • Rheology measurements
  • In vitro permeation studies (synthetic membranes/skin slice/corneas) with Franz cells
  • Photostability studies (sunlight simulators) 
  • Stability studies of disperse systems
  • Conductivity and surface tension evaluation
  • Non-invasive determination of physiological skin parameters (corneometer, sebumeter, colorimeter, glossmeter, cutometer, skin pH-meter).

 

 

Figure 3. Sunlight simulatorSunlight simulator

 

upload_cutometer.jpgCutometer 

- University Hospital Città della Salute e della Scienza di Torino, Torino 

- S.C. Farmacia Ospedaliera A.O. Ordine Mauriziano, Torino

- Candiolo Cancer Institute, FPO—IRCCS, Candiolo 

- Società Prodotti Antibiotici S.p.A

- Department of Health Sciences, Università del Piemonte Orientale, Novara 

- Department of Pharmaceutical Sciences, Università del Piemonte Orientale, Novara 

- Centro di Riferimento Oncologico (CRO) di Aviano IRCCS, Aviano 

- Neuroengineering and Neuroprosthesis Unit at the Bioengineering Institute. University Miguel Hernández (Spain)

- Department of Pharmaceutical Sciences, School of Health Sciences of Polytechnic Institute of Guarda (Guarda, Portugal)

- Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA) La Plata (Argentina)

- Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel), Prof. Ronit Satchi-Fainaro

- Research Institute for Medicines, iMed.ULisboa, Faculty of Pharmacy, University of Lisbon, Lisboa (Portugal), Prof. Helena Florindo

- Advanced Drug Delivery and Biomaterials, Louvain Drug Research Institute, UCLouvain (Belgium)

- Gliomagenesis and Microenvironment, Institute of NeuroPhysiopathology, Aix-Marseille University (France)



Progetti

Prodotti della ricerca

Wang M, Malfanti A, Bastiancich C, Preat V. (2023) Synergistic effect of doxorubicin lauroyl hydrazone derivative delivered by alpha-tocopherol succinate micelles for the treatment of glioblastoma. International journal of pharmaceutics: X 5 100147 [DOI  PMID]

Argenziano M, Bessone F, Dianzani C, Cucci MA, Grattarola M, Pizzimenti S, Cavalli R. (2022) Ultrasound-Responsive Nrf2-Targeting siRNA-Loaded Nanobubbles for Enhancing the Treatment of Melanoma. Pharmaceutics 14(2) [DOI  PMID]

Bozzato E, Tsakiris N, Paquot A, Muccioli GG, Bastiancich C, Preat V. (2022) Dual-drug loaded nanomedicine hydrogel as a therapeutic platform to target both residual glioblastoma and glioma stem cells. International journal of pharmaceutics 628 122341 [DOI  PMID]

Naked and Decorated Nanoparticles Containing H2S-Releasing Doxorubicin: Preparation, Characterization and Assessment of Their Antitumoral Efficiency on Various Resistant Tumor Cells
2022-01-01 Elena PEIRA; Daniela Chirio; Simona Sapino; Konstantin CHEGAEV; Giulia Chindamo; IRIS CHIARA SALAROGLIO; Chiara Riganti; Marina GALLARATE https://iris.unito.it/handle/2318/1885286

Chirio D, Sapino S, Chindamo G, Peira E, Vercelli C, Riganti C, Manzoli M, Gambino G, Re G, Gallarate M. (2022) Doxorubicin-Loaded Lipid Nanoparticles Coated with Calcium Phosphate as a Potential Tool in Human and Canine Osteosarcoma Therapy. Pharmaceutics 14(7) [DOI  PMID]

Chirio D, Peira E, Sapino S, Chindamo G, Oliaro-Bosso S, Adinolfi S, Dianzani C, Baratta F, Gallarate M. (2021) A New Bevacizumab Carrier for Intravitreal Administration: Focus on Stability. Pharmaceutics 13(4) [DOI PMID]

Giovannelli L, Milanesi A, Ugazio E, Fracchia L, Segale L. (2021) Effect of Methyl-beta-Cyclodextrin and Trehalose on the Freeze-Drying and Spray-Drying of Sericin for Cosmetic Purposes. Pharmaceuticals (Basel, Switzerland) 14(3) [DOI  PMID]

Peira E, Chindamo G, Chirio D, Sapino S, Oliaro-Bosso S, Rebba E, Ivanchenko P, Gallarate M. (2021) Assessment of In-Situ Gelling Microemulsion Systems upon Temperature and Dilution Condition for Corneal Delivery of Bevacizumab. Pharmaceutics 13(2) [DOI  PMID]

Scutera S, Argenziano M, Sparti R, Bessone F, Bianco G, Bastiancich C, Castagnoli C, Stella M, Musso T, Cavalli R. (2021) Enhanced Antimicrobial and Antibiofilm Effect of New Colistin-Loaded Human Albumin Nanoparticles. Antibiotics (Basel, Switzerland) 10(1) [DOI  PMID]

Argenziano M, Gigliotti CL, Clemente N, Boggio E, Ferrara B, Trotta F, Pizzimenti S, Barrera G, Boldorini R, Bessone F, Dianzani U, Cavalli R, Dianzani C. (2020) Improvement in the Anti-Tumor Efficacy of Doxorubicin Nanosponges in In Vitro and in Mice Bearing Breast Tumor Models. Cancers 12(1) [DOI  PMID]

Clemente N, Boggio E, Gigliotti LC, Raineri D, Ferrara B, Miglio G, Argenziano M, Chiocchetti A, Cappellano G, Trotta F, Caldera F, Capucchio MT, Yagi J, Rojo MJ, Reno F, Cavalli R, Dianzani C, Dianzani U. (2020) Immunotherapy of experimental melanoma with ICOS-Fc loaded in biocompatible and biodegradable nanoparticles. Journal of controlled release : official journal of the Controlled Release Society 320 112-124 [DOI  PMID]

Donalisio M, Argenziano M, Ritta M, Bastiancich C, Civra A, Lembo D, Cavalli R. (2020) Acyclovir-loaded sulfobutyl ether-beta-cyclodextrin decorated chitosan nanodroplets for the local treatment of HSV-2 infections. International journal of pharmaceutics 587 119676 [DOI  PMID]

Dianzani C, Monge C, Miglio G, Serpe L, Martina K, Cangemi L, Ferraris C, Mioletti S, Osella S, Gigliotti CL, Boggio E, Clemente N, Dianzani U, Battaglia L. (2020) Nanoemulsions as Delivery Systems for Poly-Chemotherapy Aiming at Melanoma Treatment. Cancers 12(5) [DOI  PMID]

Fathy Abd-Ellatef GE, Gazzano E, Chirio D, Hamed AR, Belisario DC, Zuddas C, Peira E, Rolando B, Kopecka J, Assem Said Marie M, Sapino S, Ramadan Fahmy S, Gallarate M, Abdel-Hamid AZ, Riganti C. (2020) Curcumin-Loaded Solid Lipid Nanoparticles Bypass P-Glycoprotein Mediated Doxorubicin Resistance in Triple Negative Breast Cancer Cells. Pharmaceutics 12(2) [DOI  PMID]

Chirio D, Peira E, Dianzani C, Muntoni E, Gigliotti CL, Ferrara B, Sapino S, Chindamo G, Gallarate M. (2019) Development of Solid Lipid Nanoparticles by Cold Dilution of Microemulsions: Curcumin Loading, Preliminary In Vitro Studies, and Biodistribution. Nanomaterials (Basel, Switzerland) 9(2) [DOI  PMID]

Conniot J, Scomparin A, Peres C, Yeini E, Pozzi S, Matos AI, Kleiner R, Moura LIF, Zupancic E, Viana AS, Doron H, Gois PMP, Erez N, Jung S, Satchi-Fainaro R, Florindo HF. (2019) Immunization with mannosylated nanovaccines and inhibition of the immune-suppressing microenvironment sensitizes melanoma to immune checkpoint modulators. Nature nanotechnology 14(9) 891-901 [DOI  PMID]

Gnaim S, Scomparin A, Eldar-Boock A, Bauer CR, Satchi-Fainaro R, Shabat D. (2019) Light emission enhancement by supramolecular complexation of chemiluminescence probes designed for bioimaging. Chemical science 10(10) 2945-2955 [DOI  PMID]

Jadhav SA, Brunella V, Sapino S, Caprarelli B, Riedo C, Chirio D, Gallarate M. (2019) Poly (N-isopropylacrylamide) based hydrogels as novel precipitation and stabilization media for solid lipid nanoparticles (SLNs). Journal of colloid and interface science 541 454-460 [DOI  PMID]

Malfanti A, Scomparin A, Pozzi S, Gibori H, Krivitsky A, Blau R, Satchi-Fainaro R, Mastrotto F, Caliceti P, Salmaso S. (2019) Oligo-guanidyl targeted bioconjugates forming rod shaped polyplexes as a new nanoplatform for oligonucleotide delivery. Journal of controlled release : official journal of the Controlled Release Society 310 58-73 [DOI  PMID]

Muntoni E, Marini E, Ahmadi N, Milla P, Ghe C, Bargoni A, Capucchio MT, Biasibetti E, Battaglia L. (2019) Lipid nanoparticles as vehicles for oral delivery of insulin and insulin analogs: preliminary ex vivo and in vivo studies. Acta diabetologica 56(12) 1283-1292 [DOI  PMID]

Muntoni E, Martina K, Marini E, Giorgis M, Lazzarato L, Salaroglio IC, Riganti C, Lanotte M, Battaglia L. (2019) Methotrexate-Loaded Solid Lipid Nanoparticles: Protein Functionalization to Improve Brain Biodistribution. Pharmaceutics 11(2) [DOI  PMID]

Nunes F, Rodrigues M, Ribeiro MP, Ugazio ECavalli R, Abollino O, Coutinho P, Araujo ARTS. (2019) Incorporation of Cro thermal water in a dermocosmetic formulation: cytotoxicity effects, characterization and stability studies and efficacy evaluation. International Journal of Cosmetic Science 41 (6), 604-612   [DOI   PMID]

Sapino S, Peira E, Chirio D, Chindamo G, Guglielmo S, Oliaro-Bosso S, Barbero R, Vercelli C, Re G, Brunella V, Riedo C, Fea AM, Gallarate M. (2019) Thermosensitive Nanocomposite Hydrogels for Intravitreal Delivery of Cefuroxime. Nanomaterials (Basel, Switzerland) 9(10) [DOI  PMID]

Caldera F, Argenziano M, Trotta F, Dianzani C, Gigliotti L, Tannous M, Pastero L, Aquilano D, Nishimoto T, Higashiyama T, Cavalli R. (2018) Cyclic nigerosyl-1,6-nigerose-based nanosponges: An innovative pH and time-controlled nanocarrier for improving cancer treatment. Carbohydrate polymers 194 111-121 [DOI  PMID]

Chirio D, Peira E, Sapino S, Dianzani C, Barge A, Muntoni E, Morel S, Gallarate M. (2018) Stearoyl-Chitosan Coated Nanoparticles Obtained by Microemulsion Cold Dilution Technique. International journal of molecular sciences 19(12) [DOI  PMID]

Ultimo aggiornamento: 01/08/2023 11:19
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