Enhancement of liposomal stability and cellular drug uptake by incorporating tributyrin into celecoxib-loaded liposomes

Abstract

Tributyrin, a triglyceride analog of short chain fatty acid butyrate, can act as a prodrug of an anticancer agent butyrate. In view of other reports that demonstrated the improved characteristics of conventional liposomes by incorporating small amount of non-phospholipids such as Tween 80, herein we sought to investigate whether the incorporation of tributyrin into the liposomal layers may provide additional advantages for liposomes as an anticancer drug carrier. Liposomes were prepared with dimyristoylphosphatidylcholine as a main phospholipid with or without addition of tributyrin. Celecoxib was loaded in liposomes as a model anticancer drug. Tween 80-incorporated liposomes were also prepared for comparison. Tributyrin-incorporated liposomes were ineffective in enhancing the skin permeation of celecoxib compared to Tween 80-incorporated ones. However, tributyrin-incorporated liposomes enhanced the entrapped celecoxib concentration to an extent comparable to Tween 80-incorporated ones. Furthermore, tributyrin-incorporated liposomes exhibited much higher stability compared to Tween 80-incorporated ones. Finally, the cellular uptake of celecoxib loaded in tributyrin-incorporated liposomes into mouse melanoma cells were more than 10-fold higher compared to that loaded in conventional- and Tween 80-incorporated liposomes. Taken together, the incorporation of tributyrin into conventional liposomes loaded with anticancer drugs may provide an advanced anticancer drug carrier delivering both drug and tributyrin.