title: Enhanced cellular uptake by "pharmaceutically oriented devices" of new simplified analogs of Linezolid with antimicrobial activity.
abstract: The aim of the present study was to enhance cellular uptake of simplified analogs of Linezolid by their incorporation into suitable delivery devices in order to improve the antimicrobial activity of these novel synthesized oxazolidin-2-one derivatives. The oxazolidin-2-one derivatives were synthesized by developing a rather simple one-pot reaction starting from oxiranylmethanol and several primary amines. Three delivery devices were prepared by following different synthetic approaches, such as single-step free radical grafting, precipitation polymerization and nano-emulsion. Finally, the antimicrobial activity of the novel synthesized compounds, without any vehicle and after their incorporation into the delivery devices, was evaluated against Escherichia coli and Saccharomyces cerevisiae by performing time-kill analyses. The synthesized oxazolidinones exhibited modest antimicrobial activity against E. coli and S. cerevisiae (MIC 16 μg/mL). A good activity was, instead, highlighted after their incorporation into the prepared delivery devices (lecithin-based nano-emulsion, poly(N-vinyl-pyrrolidone)-methacrylic acid grafted copolymer and spherical polymeric nanoparticles) (MIC≤4 μg/mL). The incorporation into suitable vehicles, indeed, reduced by 4 times the normal MICs of the newly synthesized oxazolilidin-2-ones and represents an effective strategy to overcome cellular penetration constraints.
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende (CS), Italy; Department of Computer Engineering, Modeling, Electronics and Systems, University of Calabria, 87036 Rende (CS), Italy.
authors.forename: Ortensia Ilaria
authors.initials: OI
authors.lastname: Parisi
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende (CS), Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Fiorillo
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende (CS), Italy; Department of Computer Engineering, Modeling, Electronics and Systems, University of Calabria, 87036 Rende (CS), Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Caruso
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende (CS), Italy.
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Cappello
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, University of Salerno, 84084 Fisciano (SA), Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Saturnino
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende (CS), Italy. Electronic address: francescopuoci@gmail.com.
authors.forename: Francesco
authors.initials: F
authors.lastname: Puoci
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende (CS), Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Panno
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende (CS), Italy.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Dolce
authors.affiliation: Department of Chemistry, Faculty of Science, Assiut University, 71516, Assiut, Egypt.
authors.forename: Hussein
authors.initials: H
authors.lastname: El-Kashef
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende (CS), Italy.
authors.forename: Maria Stefania
authors.initials: MS
authors.lastname: Sinicropi
mesh_terms: D000081:Acetamides / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems; D004655:Emulsions; D004926:Escherichia coli / Q000187:drug effects; D000069349:Linezolid; D008826:Microbial Sensitivity Tests; D053758:Nanoparticles; D023303:Oxazolidinones / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000187:drug effects
chemical_list: D000081:Acetamides; D000890:Anti-Infective Agents; D004655:Emulsions; D023303:Oxazolidinones; D011108:Polymers; D000069349:Linezolid
keywords: Antimicrobial activity; Drug carriers; Enhanced cellular uptake; Oxazolidinones; Simplified analogs of Linezolid