title: Improved percutaneous delivery of ketoprofen using combined application of nanocarriers and silicon microneedles.
abstract: OBJECTIVE
  The aim of our study was to evaluate the effect of designing ketoprofen-loaded nanosized spheres and combining them with solid silicon microneedles for enhanced and sustained percutaneous drug delivery.
  
  
  METHODS
  Ketoprofen-loaded nanoparticles (KET-NP) were designed by modified solvent displacement method, using poly (D, L-lactic acid) (PDLLA). All prepared nanoparticles were characterised with regard to their particle size distribution, morphology, surface properties, thermal behaviour, drug content, drug release and stability. In-vitro skin permeation studies were conducted on Franz-type diffusion cells using porcine skin treated with ImmuPatch silicon microneedles (Tyndall Nation Institute, Cork, Ireland).
  
  
  RESULTS
  The study showed that uniform nanospheres were prepared with high encapsulation efficiency and retained stable for 2 months. After an initial burst release, the PDLLA nanoparticles were capable of sustaining and controlling ketoprofen release that followed Korsmeyer-Peppas kinetics. An enhanced flux of ketoprofen was observed in the skin treated with silicon microneedles over a prolonged period of time.
  
  
  CONCLUSIONS
  Following application of silicon microneedle arrays, KET-NP were able to enhance ketoprofen flux and supply the porcine skin with drug over a prolonged (24 h) period of time. Our findings indicate that the delivery strategy described here could be used for the further development of effective and painless administration systems for sustained percutaneous delivery of ketoprofen.
authors.affiliation: School of Pharmacy, University College Cork, Cork, UK; Department of Pharmacy, Faculty of Medicine, University of Banja Luka, Banja Luka, Bosnia and Herzegovina.
authors.forename: Sonja R
authors.initials: SR
authors.lastname: Vučen
authors.forename: Gordana
authors.initials: G
authors.lastname: Vuleta
authors.forename: Abina M
authors.initials: AM
authors.lastname: Crean
authors.forename: Anne C
authors.initials: AC
authors.lastname: Moore
authors.forename: Nenad
authors.initials: N
authors.lastname: Ignjatović
authors.forename: Dragan
authors.initials: D
authors.lastname: Uskoković
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D015194:Diffusion Chambers, Culture; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D066298:In Vitro Techniques; D007660:Ketoprofen / Q000008:administration & dosage*; D064347:Microscopy, Electrochemical, Scanning; D053758:Nanoparticles / Q000737:chemistry*; D009339:Needles; D010316:Particle Size; D010539:Permeability; D012825:Silicon / Q000737:chemistry*; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D013499:Surface Properties; D013552:Swine
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D007660:Ketoprofen; D012825:Silicon
keywords: ketoprofen; microneedles; nanoparticles; skin