title: Ex vivo permeation of carprofen from nanoparticles: A comprehensive study through human, porcine and bovine skin as anti-inflammatory agent.
abstract: The purpose of this study was the development of poly(d,l-lactide-co-glycolide) acid (PLGA) nanoparticles (NPs) for the dermal delivery of carprofen (CP). The developed nanovehicle was then lyophilized using hydroxypropyl-β-cyclodextrin (HPβCD) as cryoprotectant. The ex vivo permeation profiles were evaluated using Franz diffusion cells using three different types of skin membranes: human, porcine and bovine. Furthermore, biomechanical properties of skin (trans-epidermal water loss and skin hydration) were tested. Finally, the in vivo skin irritation and the anti-inflammatory efficacy were also assayed. Results demonstrated the achievement of NPs 187.32 nm sized with homogeneous distribution, negatively charged surface (-23.39 mV) and high CP entrapment efficiency (75.38%). Permeation studies showed similar diffusion values between human and porcine skins and higher for bovine. No signs of skin irritation were observed in rabbits. Topically applied NPs significantly decreased in vivo inflammation compared to the reference drug in a TPA-induced mouse ear edema model. Thus, it was concluded that NPs containing CP may be a useful tool for the dermal treatment of local inflammation.
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Biopharmaceutics and Pharmacokinetics Unit, Faculty of Pharmacy, University of Barcelona, Joan XXIII Avenue, 08028 Barcelona, Spain; Department of Physical Chemistry, Faculty of Pharmacy, University of Barcelona, Joan XXIII Avenue, 08028 Barcelona, Spain.
authors.forename: Alexander
authors.initials: A
authors.lastname: Parra
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, University of Granada, Campus de la Cartuja Street, 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 Avenue, 08028 Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Rosselló
authors.affiliation: Centro de Investigaciones Químicas, Universidad Autónoma del Estado de Morelos, Av. Universidad No. 1001, Col Chamilpa, Cuernavaca, Morelos, Mexico, Mexico.
authors.forename: María L
authors.initials: ML
authors.lastname: Garduño-Ramírez
authors.affiliation: Centro de Investigaciones Químicas, Universidad Autónoma del Estado de Morelos, Av. Universidad No. 1001, Col Chamilpa, Cuernavaca, Morelos, Mexico, Mexico.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Abrego
authors.affiliation: Department of Physical Chemistry, Faculty of Pharmacy, University of Barcelona, Joan XXIII Avenue, 08028 Barcelona, Spain.
authors.forename: María L
authors.initials: ML
authors.lastname: García
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Biopharmaceutics and Pharmacokinetics Unit, Faculty of Pharmacy, University of Barcelona, Joan XXIII Avenue, 08028 Barcelona, Spain.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Calpena
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D002227:Carbazoles / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D002417:Cattle; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D005612:Freeze Drying; D006801:Humans; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D013552:Swine; D013755:Tetradecanoylphorbol Acetate; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D000893:Anti-Inflammatory Agents; D002227:Carbazoles; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C007005:carprofen; D013755:Tetradecanoylphorbol Acetate
keywords: Anti-inflammatory efficacy; Carprofen; Carprofen (PubChem CID: 2581); Freeze-drying; Hydroxypropyl-β-cyclodextrin (PubChem CID: 44134771; Poloxamer 188 (PubChem CID: 24751); Poly(d,l-lactide-co-glycolide) acid (PubChem CID: 23111554); Polymeric nanoparticles