title: Design and elaboration of freeze-dried PLGA nanoparticles for the transcorneal permeation of carprofen: Ocular anti-inflammatory applications.
abstract: This work aimed the design and development of poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) for the ocular delivery of Carprofen (CP) by a central rotatable composite design 2(3)+ star. NPs showed adequate size for ocular administration (189.50 ± 1.67 nm), low polydispersity (0.01 ± 0.01), negative charge surface (-22.80 ± 0.66 mV) and optimal entrapment efficiency (74.70 ± 0.95%). Physicochemical analysis confirmed that CP was dispersed inside the NPs. The drug release followed a first order kinetic model providing greater sustained CP release after lyophilization. Ex vivo permeation analysis through isolated rabbit cornea revealed that a sufficient amount of CP was retained in the tissue avoiding excessive permeation and thus, potential systemic levels. Ex vivo ocular tolerance results showed no signs of ocular irritancy, which was also confirmed by in vivo Draize test. In vivo ocular anti-inflammatory efficacy test confirmed an optimal efficacy of NPs and its potential application in eye surgery.
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Barcelona, Joan XXIII Av., 08028 Barcelona, Spain; Department of Physical Chemistry, Faculty of Pharmacy, University of Barcelona, Joan XXIII Av., 08028 Barcelona, Spain.
authors.forename: Alexander
authors.initials: A
authors.lastname: Parra
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Barcelona, Joan XXIII Av., 08028 Barcelona, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Mallandrich
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, University of Granada, Campus de la Cartuja St., 18071 Granada, Spain. Electronic address: beatrizclares@ugr.es.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Clares
authors.affiliation: Department of Physical Chemistry, Faculty of Pharmacy, University of Barcelona, Joan XXIII Av., 08028 Barcelona, Spain.
authors.forename: María A
authors.initials: MA
authors.lastname: Egea
authors.affiliation: Department of Physical Chemistry, Faculty of Pharmacy, University of Barcelona, Joan XXIII Av., 08028 Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Espina
authors.affiliation: Department of Physical Chemistry, Faculty of Pharmacy, University of Barcelona, Joan XXIII Av., 08028 Barcelona, Spain.
authors.forename: María L
authors.initials: ML
authors.lastname: García
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Barcelona, Joan XXIII Av., 08028 Barcelona, Spain.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Calpena
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D002227:Carbazoles / Q000493:pharmacokinetics*; D003315:Cornea / Q000378:metabolism*; D005612:Freeze Drying; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D014961:X-Ray Diffraction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002227:Carbazoles; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C007005:carprofen
keywords: Carprofen; Eye surgery; Factorial design; Freeze-drying; Nanoparticles; PLGA