Abstract
Lipid nanoparticles have been paid growing interest for topical application of non-steroidal anti-inflammatory drugs to increase skin penetration and to reduce side effects. Solid lipid nanoparticles and nanostructured lipid carriers of celecoxib were prepared by high-pressure homogenization technique. Transmission electron microscopy, fourier transform infrared spectroscopy, differential scanning calorimetry, photon correlation spectroscopy and laser diffraction were used for characterization of nanoparticles. Their physical stability was investigated for 6 months of storage at the room temperature, 4oC and 40oC. Nanoemulsions were also prepared at the same conditions for comparison with the aim of pyhsico-chemical characterization of nanoparticles. Spherical nanoparticles with high drug payload were obtained below 250 nm when similar particle sizes were observed for 3 months of storage at all temperatures. Low microparticle content was detected in formulations after 6 months when d(0.5) values were below 270 nm at room temperature and 4oC. 40oC was not detected as a suitable storage condition for formulations. Nanoparticles were observed to provide controlled drug release. Their release profiles fitted Korsmeyer-Peppas model indicating Fickian diffusion release (case I diffusional) as the dominant mechanism. In ex-vivo skin penetration experiments through abdominal rat skins, solid lipid nanoparticles, nanostructured lipid carriers and nanoemulsion significantly increased drug penetration rate 1.4-2.2 times higher compared to a traditional gel formulation containing celecoxib (p<0.05). Penetration profiles were significantly similar for lipid nanoparticles (p>0.05). Nanoemulsion displayed the highest drug penetration rate among nano-formulations. Lipid nanoparticles and nanoemulsion were found as good canditates in order to transport celecoxib through deeper skin layers increasing drug penetration.
Keywords: Celecoxib, controlled drug delivery, high-pressure homogenization, nanoemulsion, nanostructured lipid carriers, solid lipid nanoparticles, transdermal delivery.
Graphical Abstract
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