Arachidonic acid-modified lovastatin discoidal reconstituted high density lipoprotein markedly decreases the drug leakage during the remodeling behaviors induced by lecithin cholesterol acyltransferase.

Our previous studies indicated that drug leaked from discoidal reconstituted high density lipoprotein (d-rHDL) during the remodeling behaviors induced by lecithin cholesterol acyl transferase (LCAT) abundant in circulation, thus decreasing the drug amount delivered into the target. In this study, arachidonic acid (AA)-modified d-rHDL loaded with lovastatin (LT) were engineered as AA-LT-d-rHDL to explore whether AA modification could reduce the drug leakage during the remodeling behaviors induced by LCAT and further deliver more drug into target cells to improve efficacy. After successful preparation of AA-LT-d-rHDL with different AA modification amount, a series of in vitro remodeling behaviors were investigated. Furthermore, inhibition on macrophage-derived foam cell formation was chosen to evaluate drug efficacy of AA-LT-d-rHDL. In vitro physicochemical characterizations studies showed that all LT-d-rHDL and AA-LT-d-rHDL preparations had nano-size, negative surface charge, high entrapment efficiency (EE) and comparable drug loading efficiency (DL). With increment of AA modification amount, AA-LT-d-rHDL manifested lower reactivity with LCAT, thus significantly reducing the undesired drug leakage during the remodeling behaviors induced by LCAT, eventually exerting stronger efficacy on inhibition of macrophage-derived foam cell formation. AA-LT-d-rHDL could decrease the drug leakage during the remodeling behaviors induced by LCAT and fulfill efficient drug delivery.