Browsing by Author "Rosso, Annalisa"
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- Locust bean gum (LBG) – a potential excipient for inhalation purposes: excipient characterisation and in vitro and in vivo toxicological evaluationPublication . Pontes, Jorge Filipe; Guerreiro, Filipa; da Silva, Joana Pinto; Almeida, Maria; Rosso, Annalisa; Rosa da Costa, Ana M; Agusti, Géraldine; Lollo, Giovanna; Gaspar, Maria Manuela; Grenha, AnaDry powders proposed for lung drug delivery typically involve excipients not approved for inhalation. The physicochemical characterisation of excipients is informative regarding their interaction with different body structures. Locust Bean Gum (LBG) has been proposed for diverse applications, including inhalation, benefiting from targeting ability towards phagocytic cells owing to the presence of mannose moieties. The aim of the present study was to characterise the physicochemical parameters of LBG and, for the first time, draw a toxicological profile for this excipient. LBG from three different suppliers was evaluated and eventual changes on polymer characteristics induced by purification and microparticle production were assessed, which were observed to not occur. The commercial samples showed identical FTIR spectra, as well as TGA and DSC profiles, Mw around 3.60 × 106 Da, and Tg near − 39 ◦C. All microparticles presented similar morphology and Feret diameters around 4 μm. In vitro assays performed on respiratory (A549) cells evidenced no impact of LBG microparticles on cell viability (> 80 %) when biorelevant concentrations (≈ 0.1 mg/mL) were used. Additionally, inhalation of LBG microparticles by mice provided indications of a safe profile, without induction of allergic reactions. The basis is laid for further exploration of this material in inhalation.
- Nanocomposite sponges for enhancing intestinal residence time following oral administrationPublication . Rosso, Annalisa; Andretto, Valentina; Chevalier, Yves; Kryza, David; Sidi-Boumedine, Jacqueline; Grenha, Ana; Guerreiro, Filipa; Gharsallaoui, Adem; La Padula, Veronica; Montembault, Alexandra; David, Laurent; Briançon, Stéphanie; Lollo, GiovannaIn this work, nanocomposites that combine mucopenetrating and mucoadhesive properties in a single system are proposed as innovative strategy to increase drug residence time in the intestine following oral administration. To this aim, novel mucoadhesive chitosan (CH) sponges loaded with mucopenetrating nanoemulsions (NE) were developed via freeze-casting technique. The NE mucopenetration ability was determined studying the surface affinity and thermodynamic binding of the nanosystem with mucins. The ability of nanoparticles to penetrate across a preformed mucins layer was validated by 3D-time laps Confocal Laser Scanning Microscopy imaging. Microscopy observations (Scanning Electron Microscopy and Optical Microscopy) showed that NE participated in the structure of the sponge affecting its stability and in vitro release kinetics. When incubated with HCT 116 and Caco-2 cell lines, the NE proved to be cytocompatible over a wide concentration range. Finally, the in vivo biodistribution of the nanocomposite was evaluated after oral gavage in healthy mice. The intestinal retention of NE was highly enhanced when loaded in the sponge compared to the NE suspension. Overall, our results demonstrated that the developed nanocomposite sponge is a promising system for sustained drug intestinal delivery.
- Supersaturable self-microemulsifying delivery systems: an approach to enhance oral bioavailability of benzimidazole anticancer drugsPublication . Rosso, Annalisa; Almouazen, Eyad; Pontes, Jorge Filipe; Andretto, Valentina; Leroux, Marine; Romasko, Etienne; Azzouz-Maache, Samira; Bordes, Claire; Coste, Isabelle; Renno, Touffic; Giraud, Stephane; Briancon, Stephanie; Lollo, GiovannaThis study explored the design of supersaturable self-microemulsifying drug delivery systems (S-SMEDDS) to address poor solubility and oral bioavailability of a novel benzimidazole derivative anticancer drug (BI). Firstly, self-microemulsifying drug delivery systems SMEDDS made of Miglyol (R) 812, Kolliphor (R) RH40, Transcutol (R) HP, and ethanol were prepared and loaded with the BI drug. Upon dispersion, the systems formed neutrally charged droplets of around 20 nm. However, drug precipitation was observed following incubation with simulated gastric fluid (pH 1.2). Aiming at reducing this precipitation and enhancing drug payload, supersaturable systems were then prepared by adding 1% hydroxypropyl cellulose as precipitation inhibitor. Supersaturable systems maintained a higher amount of drug in a supersaturated state in gastric medium compared with conventional formulations and were stable in simulated intestinal medium ( pH 6.8). In vitro cell studies using Caco-2 cell line showed that these formulations reduced in a transient manner the transepithelial electrical resistance of the monolayers without toxicity. Accordingly, confocal images revealed that the systems accumulated at tight junctions after a 2 h exposure. In vivo pharmacokinetic studies carried out following oral administration of BI-loaded S-SMEDDS, SMEDDS, and free drug to healthy mice showed that supersaturable systems promoted drug absorption compared with the other formulations. Overall, these data highlight the potential of using the supersaturable approach as an alternative to conventional SMEDDS for improving oral systemic absorption of lipophilic drugs.