Improved percutaneous delivery of ketoprofen using combined application of nanocarriers and silicon microneedles

J Pharm Pharmacol. 2013 Oct;65(10):1451-62. doi: 10.1111/jphp.12118. Epub 2013 Aug 5.

Abstract

Objectives: 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).

Key findings: 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.

Keywords: ketoprofen; microneedles; nanoparticles; skin.

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Diffusion Chambers, Culture
  • Drug Carriers / chemistry*
  • Drug Compounding
  • In Vitro Techniques
  • Ketoprofen / administration & dosage*
  • Microscopy, Electrochemical, Scanning
  • Nanoparticles / chemistry*
  • Needles*
  • Particle Size
  • Permeability
  • Silicon / chemistry*
  • Skin / metabolism
  • Skin Absorption
  • Surface Properties
  • Swine

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Drug Carriers
  • Ketoprofen
  • Silicon