Novel Phenobarbital-Loaded Nanostructured Lipid Carriers for Epilepsy Treatment: From QbD to In Vivo Evaluation.

Autor:	Scioli-Montoto S; Laboratory of Bioactive Compounds Research and Development, Department of Biological Sciences, School of Exact Sciences, National University of La Plata, La Plata, Argentina.; National Council for Scientific and Technical Research (CONICET), La Plata, Argentina., Sbaraglini ML; Laboratory of Bioactive Compounds Research and Development, Department of Biological Sciences, School of Exact Sciences, National University of La Plata, La Plata, Argentina.; National Council for Scientific and Technical Research (CONICET), La Plata, Argentina., Cisneros JS; National Council for Scientific and Technical Research (CONICET), La Plata, Argentina.; Research Institute of Theoretical and Applied Physical Chemistry (INIFTA-CONICET-UNLP), Department of Chemistry, School of Exact Sciences, National University of La Plata, La Plata, Argentina., Chain CY; National Council for Scientific and Technical Research (CONICET), La Plata, Argentina.; Research Institute of Theoretical and Applied Physical Chemistry (INIFTA-CONICET-UNLP), Department of Chemistry, School of Exact Sciences, National University of La Plata, La Plata, Argentina., Ferretti V; Inorganic Chemistry Center (CEQUINOR-CONICET-UNLP), Department of Chemistry, School of Exact Sciences, National University of La Plata, La Plata, Argentina., León IE; National Council for Scientific and Technical Research (CONICET), La Plata, Argentina.; Inorganic Chemistry Center (CEQUINOR-CONICET-UNLP), Department of Chemistry, School of Exact Sciences, National University of La Plata, La Plata, Argentina.; Physiopathology Chair, Biological Sciences Department, School of Exact Sciences, National University of La Plata, La Plata, Argentina., Alvarez VA; National Council for Scientific and Technical Research (CONICET), La Plata, Argentina.; Institute of Materials Science and Technology Research (INTEMA-CONICET-UNMdP), Mar del Plata, Argentina., Castro GR; Nanomedicine Research Unit (Nanomed), Federal University of ABC (UFABC), Santo André, Brazil.; Max Planck Laboratory for Structural Biology, Chemistry and Molecular Biophysics of Rosario (MPLbioR, UNR-MPIbpC), Partner Laboratory of the Max Planck Institute for Biophysical Chemistry (MPIbpC, MPG), Center for Interdisciplinary Studies (CEI-CONICET), National University of Rosario, Rosario, Argentina., Islan GA; National Council for Scientific and Technical Research (CONICET), La Plata, Argentina.; Nanobiomaterials Laboratory, Center for Research and Development of Industrial Fermentations (CINDEFI-CONICET-UNLP), School of Exact Sciences, National University of La Plata, La Plata, Argentina., Talevi A; Laboratory of Bioactive Compounds Research and Development, Department of Biological Sciences, School of Exact Sciences, National University of La Plata, La Plata, Argentina.; National Council for Scientific and Technical Research (CONICET), La Plata, Argentina., Ruiz ME; Laboratory of Bioactive Compounds Research and Development, Department of Biological Sciences, School of Exact Sciences, National University of La Plata, La Plata, Argentina.; National Council for Scientific and Technical Research (CONICET), La Plata, Argentina.
Jazyk:	angličtina
Zdroj:	Frontiers in chemistry [Front Chem] 2022 Aug 17; Vol. 10, pp. 908386. Date of Electronic Publication: 2022 Aug 17 (Print Publication: 2022).
DOI:	10.3389/fchem.2022.908386
Abstrakt:	Pharmacological treatments of central nervous system diseases are always challenging due to the restrictions imposed by the blood-brain barrier: while some drugs can effectively cross it, many others, some antiepileptic drugs among them, display permeability issues to reach the site of action and exert their pharmacological effects. The development of last-generation therapeutic nanosystems capable of enhancing drug biodistribution has gained ground in the past few years. Lipid-based nanoparticles are promising systems aimed to improve or facilitate the passage of drugs through biological barriers, which have demonstrated their effectiveness in various therapeutic fields, without signs of associated toxicity. In the present work, nanostructured lipid carriers (NLCs) containing the antiepileptic drug phenobarbital were designed and optimized by a quality by design approach (QbD). The optimized formulation was characterized by its entrapment efficiency, particle size, polydispersity index, and Z potential. Thermal properties were analyzed by DSC and TGA, and morphology and crystal properties were analyzed by AFM, TEM, and XRD. Drug localization and possible interactions between the drug and the formulation components were evaluated using FTIR. In vitro release kinetic, cytotoxicity on non-tumoral mouse fibroblasts L929, and in vivo anticonvulsant activity in an animal model of acute seizures were studied as well. The optimized formulation resulted in spherical particles with a mean size of ca. 178 nm and 98.2% of entrapment efficiency, physically stable for more than a month. Results obtained from the physicochemical and in vitro release characterization suggested that the drug was incorporated into the lipid matrix losing its crystalline structure after the synthesis process and was then released following a slower kinetic in comparison with the conventional immediate-release formulation. The NLC was non-toxic against the selected cell line and capable of delivering the drug to the site of action in an adequate amount and time for therapeutic effects, with no appreciable neurotoxicity. Therefore, the developed system represents a promising alternative for the treatment of one of the most prevalent neurological diseases, epilepsy. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Scioli-Montoto, Sbaraglini, Cisneros, Chain, Ferretti, León, Alvarez, Castro, Islan, Talevi and Ruiz.)
Databáze:	MEDLINE
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