title: Hyaluronic acid-decorated reconstituted high density lipoprotein targeting atherosclerotic lesions.
abstract: The primary aim of our current study was to utilize hyaluronic acid (HA) to decorate reconstituted high density lipoprotein (rHDL) loaded with lovastatin (LT), termed as HA-LT-rHDL, in order to investigate whether coating HA could efficiently evade from the undesired uptake of LT-rHDL in liver mediated by scavenger receptor class B type I (SR-BI) and then greatly accumulate LT-rHDL in atherosclerotic lesions via strong HA affinity to CD44 up-regulated at inflammatory sites such as atherosclerotic lesions, thus exerting enhanced atheroprotective efficacy. In vitro characterizations indicated the successful HA decoration onto the surface of LT-rHDL, which could be indirectly verified by the increased particle size, enhanced negative surface charge and reduced in vitro drug release rate after HA decoration. Compared with rHDL without HA, HA decoration endowed rHDL with better atherosclerotic lesions targeting efficiency and lower liver accumulation, proved by results from ex vivo imaging and tissue distribution. Furthermore, atheroprotective efficacy in model animal showed that HA-LT-rHDL had the best potent efficacy than other LT preparations, which was demonstrated by the fewest atherosclerotic lesions sizes, the most minimum mean intima-media thickness (MIT), the lowest macrophage infiltration and expression of matrix metalloproteinase-9 (MMP-9), respectively. Above results demonstrated that the newly designed HA-LT-rHDL could decrease the non-targeted uptake by liver and deliver a large amount of drug into atherosclerotic lesions so as to efficiently suppress the advancement of atherosclerosis.
authors.affiliation: Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Lisha
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Mengyuan
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Shuangshuang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: jianpingliu1293@163.com.
authors.forename: Jianping
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy / Q000473:pathology*; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry; D005455:Fluorescent Antibody Technique; D006820:Hyaluronic Acid / Q000737:chemistry*; D008075:Lipoproteins, HDL / Q000378:metabolism* / Q000648:ultrastructure; D008148:Lovastatin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D008264:Macrophages / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D049329:Nanostructures / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D011817:Rabbits; D055672:Static Electricity; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D004337:Drug Carriers; D008075:Lipoproteins, HDL; D006820:Hyaluronic Acid; D008148:Lovastatin; D020780:Matrix Metalloproteinase 9
keywords: Atheroprotective efficacy; Atherosclerotic lesions targeting; CD44; HA; SR-BI; rHDL