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Context: Aceclofenac (ACE) is a systematically designed drug, developed to circumvent the concerns associated with diclofenac. But ACE is also associated with non-steroidal antiinflammatory drug (NSAIDs)-tagged side effects, although of decreased amplitude. Objective: The present study aims to develop phospholipid-based vesicles (elastic membrane vesicles; EMV and ethosomes) loaded with ACE and explore their potential in topical delivery. Methods: Elastic membrane vesicles (EMVs) were prepared by thin-film hydration method and ethosomes by cold method. The composition of both the vesicular systems was selected on the basis of vesicle density and drug entrapment. The developed systems were characterized for micromeritics, surface charge, drug entrapment, and morphology. Ex vivo permeation and retention studies on Laca mice skin were performed. In vivo pharmacodynamic evaluation was performed by tail-flick method and carrageenan-induced rat paw-edema model. During stability studies, percent drug leakage was studied. Results: The selected ratios of phospholpid:drug:stearylamine for EMVs and ethosomes were 8:1:1 and 3:1:1, respectively. The ethosomes were found to offer more vesicle density, drug loading, and deformability index as compared with that of EMVs. The drug permeation and the retention offered by both the vesicular systems were superior to that of the conventional cream; however, performance of ethosomes superseded that of EMVs. The phospholipid-based vesicles were found to be well tolerated on mice skin. Although, the in vivo performance of ethosomes was found to be better than that of EMVs in both the studied models. Conclusion: The phospholipid-based vesicular systems, especially, ethosomes can be a promising tool to enhance the delivery and safety of ACE by topical route.

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