Nanostructured Lipid Carriers for Enhancement of Oral Delivery of Ebastine: In Vitro and In Vivo Investigation

Background/Objectives: Ebastine is a second-generation non-sedative antihistamine with potent anti-inflammatory activity. The therapeutic efficacy of ebastine is limited by its low water solubility. Accordingly, this study aimed to formulate nano lipid-based systems to enhance the anti-inflammatory potential of ebastine. Methods: Nanostructured lipid carriers (NLCs) loaded with ebastine were formulated using the micro-emulsification technique. The prepared systems were characterized for particle size (PS), zeta potential (ZP), morphological features using transmission electron microscopy (TEM), entrapment efficiency (%EE), and in vitro drug release. The in vivo anti-inflammatory efficacy was also evaluated employing the carrageenan-induced paw edema model. Results: The constructed NLCs demonstrated negatively charged spherical nanoparticles with average particle sizes ranging from 146.7 nm to 293.0 nm. Ebastine was effectively trapped in the NLCs, with the recorded %EE ranging from 96.4% to 97.5%. All the fabricated NLCs revealed a sustained ebastine release behavior over 8 h compared to the aqueous drug dispersion. In vivo performance evaluations demonstrated a significant improvement in the anti-inflammatory efficacy of ebastine-loaded NLCs compared to unprocessed ebastine aqueous dispersion. This was manifested in the significant reduction of the rats’ paw edema, with the % edema inhibition reaching 31.3%, 40.2%, and 35.2% for F1, F2, and F3, respectively. However, without a blank NLC control, the isolated effect of ebastine could not be fully distinguished from that of the carrier. Additionally, histopathological examinations revealed a remarkable reduction in the inflammation score in thin and thick skin sections for NLC groups compared to the untreated negative control group. Notably, F2 and F3 showed significant improvement in thin-skin inflammation scores. Conclusions: The tested NLCs potentially demonstrated an improved anti-inflammatory efficiency compared to the free drug. The overall findings introduced NLCs as a promising nanoplatform for enhancing the pharmacodynamic efficacy of ebastine.