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The targeted delivery of therapeutics to the kidneys has a profound potential for the management of renal fibrosis. Thus, we developed a drug delivery system that targets mesangial cells by conjugating anti-alpha8 integrin to the surface of liposomes. We coloaded emodin (EMO) and diammonium glycyrrhizinate (DAG) to the immunoliposomes for combined therapy. The coloaded immunoliposomes were small size (92.4±0.4 nm), narrowly distributed, and with nearly neutral zeta potential and good stability. The encapsulation rate of EMO and DAG in immunoliposomes was 45.5±2.0% and 44.3±1.1%, respectively. Using a BCA assay, the actual number of antibody molecules attached to a single liposome was determined as being approximately 41. An in vitro release study showed that EMO and DAG could be ratiometrically released from the immunoliposomes, which means that an optimized synergistic ratio of the two drugs could be achieved. Studies on cellular uptake studies demonstrated an approximately 3-fold increase for immunoliposomes in HBZY-1 cells compared to nonconjugated liposomes. In vitro cell growth inhibition and Western Blot assay revealed that the coloaded immunoliposomes exhibited a stronger and synergistic in vitro antifibrosis effect against NIH3T3 and HBZY-1 cells in vitro. Taken together, it indicated that anti-alpha8 integrin-modified immunoliposomes for codelivery of EMO and DAG have great potential for targeting the kidneys for the treatment of renal fibrosis.

Codelivery of Emodin and Diammonium Glycyrrhizinate by Anti-alpha8 Integrin-Conjugated Immunoliposomes for the Treatment of Renal Fibrosis