Browsing by Author "Arena, Emanuela"

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Nanoencapsulation Strategies for the Delivery of Novel Bifunctional Antioxidant/Σ1 Selective Ligands
(Elsevier, 2017) Carbone, Claudia; Arena, Emanuela; Pepe, Veronica; Prezzavento, Orazio; Cacciatore, Ivana; Turkez, Hasan; Puglisi, Giovanni
Nowadays sigma-1 receptors are considered as new therapeutic objectives for central nervous system neurodegenerative diseases. Among different molecules, alpha lipoic acid has been identified as a natural potent antioxidant drug, whose therapeutic efficacy is limited by its many drawbacks, such as fast metabolism, poor bioavailability and high physico-chemical instability. Alfa-lipoic acid derivatives have been recently developed demonstrating their neuroprotective activity and effectiveness in different types of oxidative stress. In this work, two derivatives containing an amide or an ester functional group with different lipophilicity, were selected for their important affinity for sigma-1 receptors. Herein, in order to improve the in vitro stability and antioxidant effectiveness of alpha-lipoic acid derivatives, we focused our efforts in thenanoencapsulation strategies. Aqueous-core nanocapsules for the delivery of the hydrophilic compound and nanostructured lipid carrier for the lipophilic derivative, were properly designed and prepared using a direct or inverse eco-friendly organic solvent-free procedure. All nanosystems were characterized in terms of mean size, polydispersity, stability, morphology, encapsulation efficiency and in vitro release profiles. In order to evaluate the nanocarriers biocompatibility and antioxidant effectiveness, in vitro biological studies (cell viability, total antioxidant capacity and total oxidative status) were developed on primary human whole blood cell cultures, on both unloaded and derivatives-loaded nanodevices. (C) 2017 Elsevier B.V. All rights reserved.
New Bifunctional Antioxidant/Σ1 Agonist Ligands: Preliminary Chemico-Physical and Biological Evaluation
(Pergamon-Elsevier Science Ltd, 2016) Arena, Emanuela; Cacciatore, Ivana; Cerasa, Laura S.; Turkez, Hasan; Pittala, Valeria; Pasquinucci, Lorella; Prezzavento, Orazio
We previously reported bifunctional sigma-1 (sigma(1)) ligands endowed with antioxidant activity (1 and 2). In the present paper, pure enantiomers (R)-1 and (R)-2 along with the corresponding p-methoxy (6, 11), p-fluoro derivatives (7, 12) were synthesized. sigma(1) and sigma(2) affinities, antioxidant properties, and chemico-physical profiles were evaluated. Para derivatives, while maintaining strong sigma(1) affinity, displayed improved sigma(1) selectivity compared to the parent compounds 1 and 2. In vivo evaluation of compounds 1, 2, (R)-1, 7, and 12 showed sigma(1) agonist pharmacological profile. Chemico-physical studies revealed that amides 2, 11 and 12 were more stable than corresponding esters 1, 6 and 7 under our experimental conditions. Antioxidant properties were exhibited by fluoro derivatives 7 and 12 being able to increase total antioxidant capacity (TAC). Our results underline that p-substituents have an important role on sigma(1) selectivity, TAC, chemical and enzymatic stabilities. In particular, our data suggest that new very selective compounds 7 and 12 could be promising tools to investigate the disorders in which sigma(1) receptor dysfunction and oxidative stress are contemporarily involved. (C) 2016 Elsevier Ltd. All rights reserved.