title: Potential Eye Drop Based on a Calix[4]arene Nanoassembly for Curcumin Delivery: Enhanced Drug Solubility, Stability, and Anti-Inflammatory Effect.
abstract: Curcumin is an Indian spice with a wide spectrum of biological and pharmacological activities but poor aqueous solubility, rapid degradation, and low bioavailability that affect medical benefits. To overcome these limits in ophthalmic application, curcumin was entrapped in a polycationic calix[4]arene-based nanoaggregate by a simple and reproducible method. The calix[4]arene-curcumin supramolecular assembly (Calix-Cur) appeared as a clear colloidal solution consisting in micellar nanoaggregates with size, polydispersity index, surface potential, and drug loading percentage meeting the requirements for an ocular drug delivery system. The encapsulation in the calix[4]arene nanoassembly markedly enhanced the solubility, reduced the degradation, and improved the anti-inflammatory effects of curcumin compared to free curcumin in both in vitro and in vivo experiments. Calix-Cur did not compromise the viability of J774A.1 macrophages and suppressed pro-inflammatory marker expression in J774A.1 macrophages subjected to LPS-induced oxidative stress. Histological and immunohistochemical analyses showed that Calix-Cur reduced signs of inflammation in a rat model of LPS-induced uveitis when topically administrated in the eyes. Overall, the results supported the calix[4]arene nanoassembly as a promising nanocarrier for delivering curcumin to anterior ocular tissues.
authors.affiliation: Institute of Biomolecular Chemistry, National Research Council (C.N.R.) , 95126 Catania, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Granata
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina , 98166 Messina, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Paterniti
authors.affiliation: Institute of Biomolecular Chemistry, National Research Council (C.N.R.) , 95126 Catania, Italy.
authors.forename: Corrada
authors.initials: C
authors.lastname: Geraci
authors.affiliation: Institute of Biomolecular Chemistry, National Research Council (C.N.R.) , 95126 Catania, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cunsolo
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina , 98166 Messina, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina , 98166 Messina, Italy.
authors.forename: Marika
authors.initials: M
authors.lastname: Cordaro
authors.affiliation: SIFI SpA , 95025 Lavinaio, Catania, Italy.
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Blanco
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Science, University of Messina , 98166 Messina, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
authors.affiliation: Institute of Biomolecular Chemistry, National Research Council (C.N.R.) , 95126 Catania, Italy.
authors.forename: Grazia M L
authors.identifier: 0000-0003-4189-930X
authors.initials: GML
authors.lastname: Consoli
mesh_terms: D000818:Animals; D047250:Calixarenes / Q000737:chemistry*; D002460:Cell Line; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry* / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry; D007249:Inflammation / Q000188:drug therapy; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D009883:Ophthalmic Solutions / Q000737:chemistry*; D010636:Phenols / Q000737:chemistry*; D014605:Uveitis / Q000188:drug therapy
chemical_list: D004337:Drug Carriers; D009883:Ophthalmic Solutions; D010636:Phenols; C121325:calix(4)arene; D047250:Calixarenes; D003474:Curcumin
keywords: calix[4]arene; curcumin; drug delivery; inflammation; uveitis