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

Abstract:

PURPOSE: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. METHODS: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. RESULTS: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. CONCLUSION:AA-LT-d-rHDL could decrease the drug leakage during the remodeling behaviors induced by LCAT and fulfill efficient drug delivery.

journal_name

Pharm Res

journal_title

Pharmaceutical research

authors

He H,Liu L,Bai H,Wang J,Zhang Y,Zhang W,Zhang M,Wu Z,Liu J

doi

10.1007/s11095-013-1273-3

subject

Has Abstract

pub_date

2014-07-01 00:00:00

pages

1689-709

issue

7

eissn

0724-8741

issn

1573-904X

journal_volume

31

pub_type

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