title: Design of cationic lipid nanoparticles for ocular delivery: development, characterization and cytotoxicity.
abstract: In the present study we have developed lipid nanoparticle (LN) dispersions based on a multiple emulsion technique for encapsulation of hydrophilic drugs or/and proteins by a full factorial design. In order to increase ocular retention time and mucoadhesion by electrostatic attraction, a cationic lipid, namely cetyltrimethylammonium bromide (CTAB), was added in the lipid matrix of the optimal LN dispersion obtained from the factorial design. There are a limited number of studies reporting the ideal concentration of cationic agents in LN for drug delivery. This paper suggests that the choice of the concentration of a cationic agent is critical when formulating a safe and stable LN. CTAB was included in the lipid matrix of LN, testing four different concentrations (0.25%, 0.5%, 0.75%, or 1.0%wt) and how composition affects LN behavior regarding physical and chemical parameters, lipid crystallization and polymorphism, and stability of dispersion during storage. In order to develop a safe and compatible system for ocular delivery, CTAB-LN dispersions were exposed to Human retinoblastoma cell line Y-79. The toxicity testing of the CTAB-LN dispersions was a fundamental tool to find the best CTAB concentration for development of these cationic LN, which was found to be 0.5 wt% of CTAB.
authors.affiliation: 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), Vila Real, Portugal; Department of Biology and Environment, University of Trás-os-Montes e Alto Douro (UTAD), Vila Real, Portugal.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Andreani
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: 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: Division of Endocrinology, Diabetes and Metabolism, Hospital de Braga, Braga, Portugal.
authors.forename: Selma B
authors.initials: SB
authors.lastname: Souto
authors.affiliation: Centre for Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Vila Real, Portugal; Department of Biology and Environment, University of Trás-os-Montes e Alto Douro (UTAD), Vila Real, Portugal.
authors.forename: Amélia M
authors.initials: AM
authors.lastname: Silva
authors.affiliation: Faculty of Health Sciences, Fernando Pessoa University (UFP-FCS), Rua Carlos da Maia, 296, 4200-150 Porto, Portugal; Institute of Biotechnology and Bioengineering, Centre of Genetics and Biotechnology, Trás-os-Montes and Alto Douro University (IBB/CGB-UTAD), Vila Real, Portugal. Electronic address: eliana@ufp.edu.pt.
authors.forename: Eliana B
authors.initials: EB
authors.lastname: Souto
mesh_terms: D060433:Administration, Ophthalmic; D002412:Cations; D045744:Cell Line, Tumor; D000077286:Cetrimonium; D002593:Cetrimonium Compounds / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000009:adverse effects; D004355:Drug Stability; D004655:Emulsions; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles / Q000633:toxicity; D012175:Retinoblastoma / Q000378:metabolism; D018675:Toxicity Tests / Q000379:methods
chemical_list: D002412:Cations; D002593:Cetrimonium Compounds; D004337:Drug Carriers; D004655:Emulsions; D008055:Lipids; D000077286:Cetrimonium
keywords: Cytotoxicity; Lipid nanoparticles; Multiple emulsion; Ocular delivery; Turbiscan; Y-79 human retinoblastoma cells