[en] Ferulic acid (Fer) and geraniol (Ger) are natural compounds whose antioxidant and anti-inflammatory activity confer beneficial properties, such as antibacterial, anticancer, and neuroprotective effects. However, the short half-lives of these compounds impair their therapeutic activities after conventional administration. We propose, therefore, a new prodrug (Fer-Ger) obtained by a bio-catalyzed ester conjugation of Fer and Ger to enhance the loading of solid lipid microparticles (SLMs) designed as Fer-Ger delivery and targeting systems. SLMs were obtained by hot emulsion techniques without organic solvents. HPLC-UV analysis evidenced that Fer-Ger is hydrolyzed in human or rat whole blood and rat liver homogenates, with half-lives of 193.64 ± 20.93, 20.15 ± 0.75, and 3.94 ± 0.33 min, respectively, but not in rat brain homogenates. Studies on neuronal-differentiated mouse neuroblastoma N2a cells incubated with the reactive oxygen species (ROS) inductor H2O2 evidenced the Fer-Ger ability to prevent oxidative injury, despite the fact that it appears ROS-promoting. The amounts of Fer-Ger encapsulated in tristearin SLMs, obtained in the absence or presence of glucose, were 1.5 ± 0.1%, allowing the control of the prodrug release (glucose absence) or to sensibly enhance its water dissolution rate (glucose presence). These new "green" carriers can potentially prolong the beneficial effects of Fer and Ger or induce neuroprotection as nasal formulations.
Disciplines :
Chemistry Pharmacy, pharmacology & toxicology
Author, co-author :
Lerin, Lindomar Alberto ; Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via Luigi Borsari, 46, I-44121 Ferrara, Italy
Botti, Giada ; Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via Luigi Borsari, 46, I-44121 Ferrara, Italy ; Center for Translational Neurophysiology of Speech and Communication (CTNSC@UniFe), Italian Institute of Technology (IIT), Via Fossato di Mortara 19, I-44121 Ferrara, Italy
Dalpiaz, Alessandro ; Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via Luigi Borsari, 46, I-44121 Ferrara, Italy
Bianchi, Anna ; Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via Luigi Borsari, 46, I-44121 Ferrara, Italy
Ferraro, Luca ; Department of Life Sciences and Biotechnology, University of Ferrara and LTTA Center, Via Fossato di Mortara 19, I-44121 Ferrara, Italy
Chaibi, Chaimae ; Université de Liège - ULiège > TERRA Research Centre > Chemistry for Sustainable Food and Environmental Systems (CSFES) ; Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via Luigi Borsari, 46, I-44121 Ferrara, Italy
Zappaterra, Federico ; Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via Luigi Borsari, 46, I-44121 Ferrara, Italy
Meola, Domenico ; Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via Luigi Borsari, 46, I-44121 Ferrara, Italy
Giovannini, Pier Paolo; Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via Luigi Borsari, 46, I-44121 Ferrara, Italy
Pavan, Barbara ; Center for Translational Neurophysiology of Speech and Communication (CTNSC@UniFe), Italian Institute of Technology (IIT), Via Fossato di Mortara 19, I-44121 Ferrara, Italy ; Department of Neuroscience and Rehabilitation-Section of Physiology, University of Ferrara, Via L. Borsari 46, I-44121 Ferrara, Italy
Language :
English
Title :
Characterization and Hydrolysis Studies of a Prodrug Obtained as Ester Conjugate of Geraniol and Ferulic Acid by Enzymatic Way.
Publication date :
06 June 2024
Journal title :
International Journal of Molecular Sciences
ISSN :
1661-6596
eISSN :
1422-0067
Publisher :
Multidisciplinary Digital Publishing Institute (MDPI)
This research was (i) supported by the European Union\u2014PON Ricerca e Innovazione 2014\u20132020 ai sensi dell\u2019art. 24, comma 3, lett. (a), della Legge 30 dicembre 2010, n. 240 es.m.i. e del D.M. 10 agosto 2021 n. 1062 (2021-PON-DM-1062-LL-RIC) and (ii) funded by the University of Ferrara, Italy (2022-FAR.L-DA_018, A.D.; 2022-FAR.L-PB_001, B.P.), in the frame of Projects FAR2022.
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