Diclofenac diethylamine nanosystems-loaded bigels for topical delivery: development, rheological characterization, and release studies

The objective of this study was to develop novel topical drug delivery systems of the nonsteroidal anti-inflammatory drug diclofenac diethylamine (DDEA). Toward this objective, DDEA was loaded into two nanosystems, the oil in water (O/W) nanoemulsion (DDEA–NE) and the gold nanorods (GNR) that were conjugated to DDEA, forming DDEA–GNR. The DDEA–NE and DDEA–GNR were characterized in terms of particle size, zeta potential, morphology, thermodynamic stability, DDEA loading efficiency, and UV–Vis spectroscopy. These nanosystems were then incorporated into the biphasic gel-based formulations (bigels) for topical delivery. The rheological characterization and release studies of the DDEA NE– and DDEA GNR–incorporated bigels were performed and compared to those of DDEA traditional bigel. DDEA–NE exhibited a droplet size 15.2 ± 1.5 nm and zeta potential −0.37 ± 0.06 mV. The particle size of GNR was approximately 66 nm × 17 nm with an aspect ratio of approximately 3.8. The bigels showed composition–dependent viscoelastic properties, which in turn play a vital role in determining the rate and mechanism of DDEA release from the bigels. Bigels showed a controlled-release pattern where 61.6, 91.7, and 50.0% of the drug was released from DDEA traditional bigel, DDEA NE–incorporated bigel, and DDEA GNR–incorporated bigel, respectively, after 24 h. The ex vivo permeation studies showed that the amount of DDEA permeated through excised skin was relatively low, between 2.7% and 18.2%. The results suggested that the incorporation of the nanosystems NE and GNR into bigels can potentially improve the topical delivery of DDEA.