Potential novel drug carriers for inner ear treatment: hyperbranched polylysine and lipid nanocapsules

AIM: Treatment of sensorineural hearing loss could be advanced using novel drug carriers such as hyperbranched polylysine (HBPL) or lipid nanocapsules (LNCs). This study examined HBPL and LNCs for their cellular uptake and possible toxicity in vitro and in vivo as the first step in developing novel nanosized multifunctional carriers. METHOD: Having incubated HBPL and LNCs with fibroblasts, nanoparticle uptake and cell viability were determined by confocal laser scanning microscopy, fluorescence measurements and neutral red staining. In vivo, electrophysiology, confocal laser scanning microscopy and cytocochleograms were performed for nanoparticle detection and also toxicity studies after intracochlear application. RESULTS: Both nanoparticles were detectable in the fibroblasts\u27 cytoplasm without causing cytotoxic effects. After in vivo application they were visualized in cochlear cells, which did not lead to a change in hearing threshold or loss of hair cells. Biocompatibility and traceability were demonstrated for HBPL and LNCs. Thus, they comply with the basic requirements for drug carriers for potential application in the inner ear

Dendritic and hyperbranched polyamides

This article discusses the synthesis and properties of dendritic and hyperbranched polyamides. The first part of the article focuses on peptide dendrimers and starts with providing an overview of the synthetic pathways that have been used to prepare dendrimers based on both natural and nonnatural amino acids. After that, the possible use of peptide dendrimers for medical and biological applications, in catalysis, chromatography and encapsulation as well as their supramolecular properties will be discussed. The second part of the article concentrates on the synthesis and properties of hyperbranched polyamides. Hyperbranched polyamides based on both aliphatic and aromatic monomers will be discussed and examples of applications of these materials as rheology modifiers or as supports for the preparation of nanoparticles will be presented. In the third and final part of the article, alternative highly branched polyamide architectures will be discussed, which are not obtained in a one step reaction, but which are produced via iterative protocols based on the ring-opening polymerization of α-amino acid N-carboxyanhydrides. © 2008 Elsevier Ltd. All rights reserved

Aromatic copolyester-based nano-biocomposites

Biodegradable polymers are one of the most promising ways to replace non-degradable polymers. But, to be a real alternative to classical synthetic polymers and find applications, biopolymer (biodegradable polymer) properties have to be enhanced. Nano-biocomposites, which are obtained by incorporation of nanofillers into a biomatrix, are an interesting way to achieve these improvements. Modified and unmodified montmorillonites have been introduced into a biodegradable aromatic copolyester, poly(butyleneadipate-co-terephthalate) (PBAT). Structural characterization, thermal and mechanical tests have been carried out to understand better the relations between the nanofillers structuring and the final nano-biocomposite properties. Main results show that clay incorporation and the obtained intercalated structures improve PBAT properties (enhanced thermal stability, increased stiffness) and thus may increase the attractiveness of this biopolymer. © Springer Science+Business Media, Inc. 2006

RUOLI DEI TOCOFEROLI IN GRANO E POMODORO: EFFETTI DI STRESS DIVERSI

La vitamina E è spesso riguardata esclusivamente come alfa-tocoferolo. In realtà essa comprende almeno quattro forme: alfa-, beta-, gamma- e delta-tocoferolo. Le forme che tra queste rivestono un ruolo maggiore come antiossidanti liposolubili sono l’alfa- ed il gamma-tocoferolo. Queste ultime due forme sono anche le più studiate e in vitro risultano possedere la stessa capacità di inibire la perossidazione lipidica in liposomi unilamellari (Wang and Quinn 1999). Tuttavia il gamma-tocoferolo presenta anche un’azione importante nel proteggere le cellule non solo contro i radicali liberi dell’ossigeno ma anche contro quelli azotati come il perossinitrito. Essendo un buon “nitro trap” il gamma-tocoferolo è considerato attualmente “l’altra vitamina E” importante per la salute umana (Navari-Izzo, comunicazione personale). Tradizionalmente la determinazione del tocoferolo è fatta tramite HPLC dotato di detector fluorimetrico. Nel nostro laboratorio l’abbiamo invece eseguita in fase inversa utilizzando un detector elettrochimico a grafite a +0.6 V. Allo scopo di chiarire il ruolo protettivo delle varie specie di tocoferoli in condizioni di stress, la loro determinazione è stata eseguita in pianticelle di grano (Triticum durum) cresciute in soluzione idroponica per 14 giorni ed incubate al momento del prelievo in una soluzione di CuSO4 100 uM per tempi diversi (da un minuto a 16 ore). Una volta chiarita la loro importanza in condizioni di stress ossidativo la determinazione di alfa-, gamma- e delta- tocoferolo è stata eseguita su alcune linee di pomodoro (Lycopersicon esculentum) cresciuto in condizioni di crescente salinità (EC = 3, 8 mS/cm). Lo scopo è stato quello di trasferire le conoscenze del loro ruolo in condizioni stressanti alla qualità del prodotto alimentare. Infatti nelle bacche di pomodoro i tocoferoli hanno il duplice ruolo di proteggere il tessuto vegetale dagli effetti dello stress ossidativo e quello salutistico. La variazione delle quantità di tocoferoli migliora infatti la qualità del prodotto, aumentandone le proprietà antiossidanti. In grano l’alfa-tocoferolo risultava presente, oltre che nei cloroplasti come generalmente accettato, anche nel plasmalemma delle radici in quantità paragonabili a quelle ritrovate nelle membrane subcellulari di ratto quali i lisosomi (Buttriss e Diplock 1988). Le forme maggiormente presenti nelle radici e foglie di grano e nelle bacche di pomodoro erano l’alfa- ed il gamma-tocoferolo mentre in grano il delta-tocoferolo era dieci volte inferiore rispetto alle altre due forme che erano presenti nelle stesse quantità

Evaluation of hyperbranched Poly-L-Lysine uptake and toxicity on inner ear derived cell line as a function of concentration and architecture

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Evaluation of cell viability and cell toxicity in PC12 and OCk-3 as a function of polycation concentration and architecture

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Uptake and toxicity tests of hyperbranched poly-l-lysine on PC12 and OCk-3 cells

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Hyperverzweigte Polylysin-Nanopartikel und Lipidnanokapseln als neuartige drug-delivery Systeme sind im Innenohr nachweisbar

W. Ling's Foden box lorry - registration HKM38 - photographed 18 September 1961. Digitisation and record funded by the Pilgrim Trust