title: PEGylated PLGA nanospheres optimized by design of experiments for ocular administration of dexibuprofen-in vitro, ex vivo and in vivo characterization.
abstract: Dexibuprofen-loaded PEGylated PLGA nanospheres have been developed to improve the biopharmaceutical profile of the anti-inflammatory drug for ocular administration. Dexibuprofen is the active enantiomer of ibuprofen and therefore lower doses may be applied to achieve the same therapeutic level. According to this, two batches of nanospheres of different drug concentrations, 0.5 and 1.0mg/ml respectively, have been developed (the latter corresponding to the therapeutic ibuprofen concentration for inflammatory eye diseases). Both batches were composed of negatively charged nanospheres (--14.1 and --15.9mV), with a mean particle size below 200nm, and a high encapsulation efficiency (99%). X-ray, FTIR, and DSC analyses confirmed that the drug was dispersed inside the matrix of the nanospheres. While the in vitro release profile was sustained up to 12h, the ex vivo corneal and scleral permeation profile demonstrated higher drug retention and permeation in the corneal tissue rather than in the sclera. These results were also confirmed by the quantification of dexibuprofen in ocular tissues after the in vivo administration of drug-loaded nanospheres. Cell viability studies confirmed that PEGylated-PLGA nanospheres were less cytotoxic than free dexibuprofen in the majority of the tested concentrations. Ocular in vitro (HET-CAM test) and in vivo (Draize test) tolerance assays demonstrated the non-irritant character of both nanosphere batches. In vivo anti-inflammatory effects were evaluated in albino rabbits before and after inflammation induction. Both batches confirmed to be effective to treat and prevent ocular inflammation.
authors.affiliation: Department of Physical Chemistry, Faculty of Pharmacy, University of Barcelona, Barcelona 08028, Spain; Institute of Nanoscience and Nanotechnology (IN2UB), Faculty of Pharmacy, University of Barcelona, Barcelona 08028, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Sánchez-López
authors.affiliation: Department of Physical Chemistry, Faculty of Pharmacy, University of Barcelona, Barcelona 08028, Spain; Institute of Nanoscience and Nanotechnology (IN2UB), Faculty of Pharmacy, University of Barcelona, Barcelona 08028, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Egea
authors.affiliation: Department of Physical Chemistry, Faculty of Pharmacy, University of Barcelona, Barcelona 08028, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Cano
authors.affiliation: Department of Physical Chemistry, Faculty of Pharmacy, University of Barcelona, Barcelona 08028, Spain; Institute of Nanoscience and Nanotechnology (IN2UB), Faculty of Pharmacy, University of Barcelona, Barcelona 08028, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Espina
authors.affiliation: Institute of Nanoscience and Nanotechnology (IN2UB), Faculty of Pharmacy, University of Barcelona, Barcelona 08028, Spain; Department of Biopharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Barcelona, Barcelona 08028, Spain.
authors.forename: A C
authors.initials: AC
authors.lastname: Calpena
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry, Faculty of Pharmacy, University of Barcelona, Barcelona 08028, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), University of Barcelona, Barcelona 08028, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Ettcheto
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry, Faculty of Pharmacy, University of Barcelona, Barcelona 08028, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), University of Barcelona, Barcelona 08028, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Camins
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra (FFUC), Polo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal.
authors.forename: E B
authors.initials: EB
authors.lastname: Souto
authors.affiliation: Department of Biology and Environment, School of Life and Environmental Sciences, (ECVA, UTAD), University of Trás-os-Montes and Alto Douro, Quinta de Prados, Vila Real 5001-801, Portugal; Centre for the Research and Technology of Agro-Environmental and Biological Sciences, University of Trás-os-Montes and Alto Douro, CITAB-UTAD, Vila-Real 5001-801, Portugal.
authors.forename: A M
authors.initials: AM
authors.lastname: Silva
authors.affiliation: Department of Physical Chemistry, Faculty of Pharmacy, University of Barcelona, Barcelona 08028, Spain; Institute of Nanoscience and Nanotechnology (IN2UB), Faculty of Pharmacy, University of Barcelona, Barcelona 08028, Spain. Electronic address: marisagarcia@ub.edu.
authors.forename: M L
authors.initials: ML
authors.lastname: García
mesh_terms: D060433:Administration, Ophthalmic; D000818:Animals; D001682:Biological Availability; D016923:Cell Death / Q000187:drug effects; D003315:Cornea / Q000187:drug effects; D065546:Drug Liberation; D007052:Ibuprofen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D007249:Inflammation / Q000473:pathology; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D054118:Nanospheres / Q000737:chemistry*; D010539:Permeability; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D012590:Sclera / Q000187:drug effects
chemical_list: D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; C539402:dexibuprofen; D007052:Ibuprofen
keywords: Dexibuprofen; Dexibuprofen (PubChem CID: 39912); Drug delivery; Ethylene glycol (PubChem CID: 174); Glycolic acid (PubChem CID: 757); Inflammation; Lactic acid (PubChem CID: 612); Nanospheres; PEG; PLGA; Polyvinyl alcohol (PubChem CID: 11199)