Effect of nanostructured lipid carriers on transdermal delivery of tenoxicam in irradiated rats

Abstract

Transdermal delivery of non-steroidal anti-inflammatory drugs (NSAIDs) is an effective route of drug administration, as it directs the drug to the inflamed site with reduced incidence of systemic adverse effects such as gastric hemorrhage and ulcers. Tenoxicam (TNX) is a member of NSAIDs that are marketed only as oral tablets due to very poor absorption through the skin. The current study intended to formulate and characterize a hydrogel loaded with nanostructured lipid carriers (NLCs) to enhance the transdermal delivery of TNX. Six formulations of TNX were formulated by slight modifications of high shear homogenization and ultrasonication method. The selected formula was characterized for their particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE), in-vitro drug release and ex-vivo skin permeation studies. Moreover, the effectiveness of the developed formula was studied in-vivo using carrageenan-induced paw edema and hyperalgesia model in irradiated rats. Formula F4 was chosen from six formulations, as the average diameter was 679.4 ± 51.3 nm, PDI value of about 0.02, zeta potential of -4.24 mV, EE of 92.36%, globules nanoparticles without aggregations and absence of interactions in the developed formula. Additionally, the in-vivo study showed the efficacy of formula F4 (TNX-NLCs hydrogel) equivalent to oral TNX in reducing the exaggerated inflammatory response induced by carrageenan after irradiation. In conclusion, the present findings suggest that TNX-NLCs hydrogel could be a potential transdermal drug delivery system alternative to the oral formulation for the treatment of various inflammatory conditions.

Keywords: Tenoxicam; carrageenan; irradiated rats; nanostructured lipid carriers; transdermal delivery.

Figure 1.

In-vitro release of tenoxicam (TNX) from tested formulations.

Figure 2.

Transmission electron micrographs of the tenoxicam-nanostructured lipid carriers (TNX-NLCs, F4).

Figure 3.

Fourier transform infrared spectroscopy (FTIR) spectra of pure tenoxicam (TNX), physical mixture of solid components, and F4.

Figure 4.

In-vitro drug release of tenoxicam (TNX) form the hydrogel.

Figure 5.

Skin permeation of tenoxicam (TNX) across natural rat skin using F4 formula.

Figure 6.

Effect of tenoxicam-nanostructured lipid carriers (TNX-NLCs) hydrogel against carrageenan-induced (A) paw edema and (B) hyperalgesia in irradiated rats. Statistical analysis was carried out by one-way ANOVA test. All values were expressed as mean ± s.e.m (n = 6). *Denotes statistical significance at p < .05 vs normal group. #denotes statistical significance at p < .05 vs inflamed group. @denotes statistical significance at p < .05 vs inflamed irradiated group.

Figure 7.

Photomicrographs of paw tissue (H & E, 100×). (A) Normal group, showing two articular cartilages separated by normal joint space with normal synovial membrane. (B) Inflamed group, showing pannus formation (small arrow) and marked edema (large arrow). (C) Inflamed irradiated, showing pannus formation (small arrow), necrosis of cartilage (large arrow) and edema with inflammatory cells infiltration (arrowhead). (D) Inflamed irradiated group treated with blank hydrogel, showing edema (small arrow) and inflammatory cells infiltration (large arrow). (E) Pure tenoxicam (TNX) hydrogel showing the accumulation of inflammatory exudate (arrow). (F) Tenoxicam-nanostructured lipid carriers (TNX-NLCs) hydrogel, showing no histopathological changes. (G) Oral TNX, showing pannus formation (small arrow) and edema (large arrow).

Figure 8.

Effect of tenoxicam-nanostructured lipid carriers (TNX-NLCs) hydrogel on (A) the serum level of thiobarbituric acid reactive substances (TBARS, mmol/l), (B) the blood level of reduced glutathione (GSH, mg/ml), (C) total nitrate/nitrite (NOx, µmol/l) and (D) tumor necrosis factor-alpha (TNF-α, pg/ml) in inflamed irradiated rats. Statistical analysis was carried out by one-way ANOVA test. All values were expressed as mean ± s.e.m (n = 6). *Denotes statistical significance at p < .05 vs normal group. #denotes statistical significance at p < .05 vs inflamed group. @denotes statistical significance at p < .05 vs inflamed irradiated group.