title: Structure and remodeling behavior of drug-loaded high density lipoproteins and their atherosclerotic plaque targeting mechanism in foam cell model.
abstract: This study is one of the first to test the relationship of formulation and structure of reconstituted high density lipoproteins (rHDL), drug behavior involved in remolding process and their targeting mechanism in a foam cell model. Tanshinone IIA-loaded rHDL (TA-rHDL) with different formulations and techniques were prepared and characterized. The targeting mechanism and drug behavior involved in remolding process were undertaken using a foam cell model. TA-rHDL prepared with cholesteryl ester (CE) and glycerol trioleate (TG) were spheres, or else discs. Guanidine hydrochloride denaturation experiments showed increased stability with TA-rHDL, compared to free apos. Phagocytosis tests demonstrated that the spherical TA-rHDL had targeting effect for foam cells through the scavenger receptor-BI and CE-TG interchange with TG-rich lipoproteins pathway under cholesteryl ester transfer protein. Discoidal TA-rHDL could reconstruct to spheres and target via a similar route as TA-rHDL spheres, showing a higher targeting efficiency. Lipophilic Tanshinone IIA could be re-entrapped in rHDL after remolding from discs to spheres and uptaken more by foam cells. Discoidal rHDL may serve as potential nanocarriers for targeting lipophilic cardiovascular drugs to atherosclerosis plaque.
authors.affiliation: Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Wen-Li
authors.initials: WL
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiao
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Liu
authors.forename: Zi-Mei
authors.initials: ZM
authors.lastname: Wu
authors.forename: Xiao
authors.initials: X
authors.lastname: Gu
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Xu
authors.forename: Hui
authors.initials: H
authors.lastname: Lu
mesh_terms: D045784:Abietanes / Q000008:administration & dosage*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D002460:Cell Line; D002788:Cholesterol Esters / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D019791:Guanidine / Q000737:chemistry; D008074:Lipoproteins / Q000737:chemistry; D008075:Lipoproteins, HDL / Q000737:chemistry*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D053758:Nanoparticles; D010587:Phagocytosis / Q000187:drug effects; D058226:Plaque, Atherosclerotic / Q000188:drug therapy* / Q000473:pathology; D014304:Triolein / Q000737:chemistry
chemical_list: D045784:Abietanes; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002788:Cholesterol Esters; D004337:Drug Carriers; D008074:Lipoproteins; D008075:Lipoproteins, HDL; C034366:discoidal lipoproteins; C021751:tanshinone; D014304:Triolein; D019791:Guanidine