Influence of Poloxamer 188 on Anti-Inflammatory and Analgesic Effects of Diclofenac-Loaded Nanoemulsion: Formulation, Optimization and in Vitro/in Vivo Evaluation.

In this study, a polymer-stabilized nanoemulsion (PNE) was developed to improve the inflammatory and analgesic activities of diclofenac (DA). DA-PNEs were prepared from sesame oil and poloxamer 188 (P188), polysorbate 80, and span 80 as emulsifiers and optimized by a systematic multi-objective optimization method. The developed DA-PNEs exhibited thermodynamical stability with low viscosity. The mean diameter, PDI, surface charge, and entrapment efficiency of DA-PNEs were 122.49±3.42 nm, 0.226±0.08, -47.3 ± 3.6 mV, and 93.57±3.4 %, respectively. The cumulative in vitro release profile of DA-PNEs was significantly higher than the neat drug in simulated gastrointestinal fluids. The anti-inflammatory activities of DA-PNEs were evaluated in the λ-carrageenan-induced paw edema model. To investigate the effect of P188 on analgesic and anti-inflammatory activities, a formulation without P188 was also prepared and named DA-NEs. Following oral administration, DA-PNEs showed a significantly higher (p<0.05) effect in reducing pain and inflammation symptoms as compared to free diclofenac and DA-NEs. Moreover, histopathological examination confirmed that DA-PNEs meaningfully reduced the extent of paw edema, comparable to that of DA. Taken together, the findings of the in vitro and in vivo studies suggest that diclofenac-loaded P188-stabilized nanoemulsion can be considered a potential drug delivery system for treating and controlling inflammatory disorders and alleviating pains.