title: Physicochemical characterization of epigallocatechin gallate lipid nanoparticles (EGCG-LNs) for ocular instillation.
abstract: The encapsulation of epigallocatechin gallate (EGCG) in lipid nanoparticles (LNs) could be a suitable approach to avoid drug oxidation and epimerization, which are common processes that lead to low bioavailability of the drug limiting its therapeutic efficacy. The human health benefits of EGCG gained much interest in the pharmaceutical field, and so far there are no studies reporting its encapsulation in LNs. The purpose of this study has been the development of an innovative system for the ocular delivery of EGCG using LNs as carrier for the future treatment of several diseases, such as dry eye, age-related macular degeneration (AMD), glaucoma, diabetic retinopathy and macular oedema. LNs dispersions have been produced by multiple emulsion technique and previously optimized by a factorial design. In order to increase ocular retention time and mucoadhesion by electrostatic attraction, two distinct cationic lipids were used, namely, cetyltrimethylammonium bromide (CTAB) and dimethyldioctadecylammonium bromide (DDAB). EGCG has been successfully loaded in the LNs dispersions and the nanoparticles analysis over 30 days of storage time predicted a good physicochemical stability. The particles were found to be in the nanometer range (<300 nm) and all the evaluated parameters, namely pH, osmolarity and viscosity, were compatible to the ocular administration. The evaluation of the cationic lipid used was compared regarding physical and chemical parameters, lipid crystallization and polymorphism, and stability of dispersion during storage. The results show that different lipids lead to different characteristics mainly associated with the acyl chain composition, i.e. double lipid shows to have influence in the crystallization and stability. Despite the recorded differences between DTAB and DDAB, both cationic LNs seem to fit the parameters for ocular drug delivery.
authors.affiliation: CEBIMED, Research Centre for Biomedicine, Fernando Pessoa University, UFP-FCS, Praça 9 de Abril, 349, P-4249-004 Porto, Portugal; Faculty of Health Sciences, Fernando Pessoa University, UFP-FCS, Rua Carlos da Maia, 296, 4200-150 Porto, Portugal.
authors.forename: Joana F
authors.initials: JF
authors.lastname: Fangueiro
authors.affiliation: Faculty of Health Sciences, Fernando Pessoa University, UFP-FCS, Rua Carlos da Maia, 296, 4200-150 Porto, Portugal; Centre for Research and Technology of Agro-Environmental and Biological Sciences, CITAB, University of Trás-os-Montes e Alto Douro, UTAD, Quinta de Prados, 5000-801 Vila Real, Portugal; Department of Biology and Environment, University of Trás-os-Montes e Alto Douro, UTAD, Quinta de Prados, 5000-801 Vila Real, Portugal.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Andreani
authors.affiliation: Electron Microscopy Unit, University of Trás-os-Montes e Alto Douro, UTAD, Quinta de Prados, 5000-801 Vila Real, Portugal.
authors.forename: Lisete
authors.initials: L
authors.lastname: Fernandes
authors.affiliation: Department of Physical Chemistry, Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08028 Barcelona, Spain; Institute of Nanoscience and Nanotechnology, University of Barcelona, Av. Joan XXIII s/n, 08028 Barcelona, Spain.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Garcia
authors.affiliation: Department of Physical Chemistry, Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08028 Barcelona, Spain; Institute of Nanoscience and Nanotechnology, University of Barcelona, Av. Joan XXIII s/n, 08028 Barcelona, Spain.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Egea
authors.affiliation: Centre for Research and Technology of Agro-Environmental and Biological Sciences, CITAB, University of Trás-os-Montes e Alto Douro, UTAD, Quinta de Prados, 5000-801 Vila Real, Portugal; Department of Biology and Environment, University of Trás-os-Montes e Alto Douro, UTAD, Quinta de Prados, 5000-801 Vila Real, Portugal.
authors.forename: Amélia M
authors.initials: AM
authors.lastname: Silva
authors.affiliation: CEBIMED, Research Centre for Biomedicine, Fernando Pessoa University, UFP-FCS, Praça 9 de Abril, 349, P-4249-004 Porto, Portugal; Faculty of Pharmacy of University of Coimbra (FFUC), Polo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal. Electronic address: ebsouto@ff.uc.pt.
authors.forename: Eliana B
authors.initials: EB
authors.lastname: Souto
mesh_terms: D060433:Administration, Ophthalmic; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry; D000077286:Cetrimonium; D002593:Cetrimonium Compounds / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry
chemical_list: D002593:Cetrimonium Compounds; D004337:Drug Carriers; D008055:Lipids; D000644:Quaternary Ammonium Compounds; C506939:dimethyldinonylammonium bromide; D002392:Catechin; C045651:epigallocatechin gallate; D000077286:Cetrimonium
keywords: Catechins; Cationic lipid; Epigallocatechin gallate; Lipid nanoparticles; Multiple emulsion; Ocular delivery