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

Abstract

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.

Keywords: Nanosystems; bigels; gold nanorods; nanoemulsion; rheology; topical delivery.