pH-Controlled Liposomes for Enhanced Cell Penetration in Tumor Environment

An innovative pH-switchable colloidal system that can be exploited for site-selective anticancer drug delivery has been generated by liposome decoration with a new novel synthetic non-peptidic oligo-arginine cell-penetration enhancer (CPE) and a quenching PEGylated counterpart that detaches from the vesicle surface under the acidic conditions of tumors. The CPE module (Arg(4)-DAG) is formed by four arginine units conjugated to a first-generation (G1) 2,2-bis(hydroxymethyl)propionic acid (bis-MPA)/2,2-bis(aminomethyl)propionic acid (bis-AMPA) polyester dendron terminating with 1,2-distearoyl-3-azidopropane for liposome bilayer insertion. The zeta potential of the Arg(4)-DAG-decorated liposomes increased up to +32 mV as the Arg(4)-DAG/lipids molar ratio increased. The Arg(4)-DAG liposome shielding at pH 7.4 was provided by methoxy-PEGS(5 kDa)-polymethacryloyl sulfadimethoxine (mPEG(5) (kDa)-SDM8) with 7.1 apparent pK(a). Zeta potential, surface plasmon resonance and synchrotron small-angle X-ray scattering analyses showed that at pH 7.4 mPEG(5) (kDa)-SDM8 associates with polycationic Arg(4)-DAG-decorated liposomes yielding liposomes with neutral zeta potential. At pH 6.5, which mimics the tumor environment, mPEG(5) (kDa)-SDM8 detaches from the liposome surface yielding Arg(4)-DAG exposure. Flow cytometry and confocal microscopy showed a 30-fold higher HeLa cancer cell association of the Arg(4)-DAG-decorated liposomes compared to non-decorated liposomes. At pH 7.4, the mPEG(5) (kDa)-SDM8-coated liposomes undergo low cell association while remarkable cell association occurred at pH 6.5, which allowed for the controlled intracellular delivery of model macromolecules and small molecules loaded in the liposome under tumor conditions.Peer reviewe

Evaluation of intra-aneurysmal hemodynamics after flow diverter placement in a patient-specific aneurysm model

BACKGROUND: The growth and rupture of cerebral aneurysms is intrinsically related to the hemodynamics prevailing in the diseased area. Therefore, a better understanding of intra-aneurysmal hemodynamics is essential for developing effective treatment methods. OBJECTIVE: The intention of this study was to evaluate the intra-aneurysmal flow and flow reduction induced by flow diverters in a true-to-scale elastic aneurysm model, obtained from real patient data. METHODS: Based on the computed tomography angiography (CTA) data of a fusiform aneurysm of a 34 year old patient, an elastic silicon rubber model of the aneurysm was produced. A physiologic pulsatile flow was created with a circulatory experimental set-up, and a non-Newtonian perfusion fluid was used as a substitute for human blood. Hemodynamics were measured by LDA before and after flow diverter implantation. RESULTS: Implantation of a flow diverter device resulted in a reduction of intra-aneurysmal maximum flow velocities of 97.8% at the inflow zone, 89.1% in the dome and 89.3% at the outflow zone, when compared to the native model. A significant reduction of 94% in the mean intra-aneurysmal velocity was found. CONCLUSIONS: This promising methodology can optimize patient treatment and will correlate with computational simulations to evaluate their reliability

Giovanni Maroni, l'ultimo madrigalista estense prima della devoluzione

Questo volume a cura di Daniele Biancardi, Saggi ariosteschi. I primi 500 anni dell’Orlando Furioso, raccoglie gli Atti del Convegno “Ariosto e il suo tempo”, tenutosi a Bondeno (FE) il 18 giugno 2016. La presente preziosa pubblicazione, peraltro ricca di numerose illustrazioni, accoglie esemplari studî, frutto di approfondite ricerche, colte riflessioni e rare competenze, di: Marco Bertozzi, Dennis Looney, Andrea Marchesi, Lucio Scardino, Enrico Scavo, Daniele Biancardi, Alberto Balasso, Marco Dorigatti

Recueil des actes administratifs de la Délégation générale du Gouvernement en Algérie : Lois et décrets...

28 octobre 19581958/10/28 (A1,N27)-1958/10/28

Preoperative velocity distribution for central cross-section of B01 aneurysm.

<p>a) CFD simulation; b) MRI measurement.</p

Preoperative velocity distribution for central cross-section of B02 aneurysm.

<p>a) CFD simulation; b) MRI measurement.</p

Pre-operative distribution of normalized wall shear stress in aneurysm models.

<p>a)—B01; b)—B02; c)—A01.</p

Velocity distribution for central cross-section of A01 aneurysm after flow-diverter placement.

<p>a) CFD simulation; b) MRI measurement.</p

Institutions de physique. Tome 1 / , par B. G. Sage,...

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