title: Nanoscaled polyion complex micelles for targeted delivery of recombinant hirudin to platelets based on cationic copolymer.
abstract: Polyion complex (PIC) micelles based on methoxy poly(ethylene glycol)-grafted-chitosan (mPEG-g-chitosan) and Arg-Gly-Asp conjugated poly(ethylene glycol)-grafted-chitosan (RGD-PEG-g-chitosan) were designed as carriers for platelet-targeted delivery of recombinant hirudin variant-2 (rHV2). The rHV2-loaded plain PIC micelles (mPIC micelles) and RGD conjugated PIC micelles (RGD-PIC micelles) were successfully prepared with mean size of 30.9 +/- 0.5 nm and 41.9 +/- 1.8 nm, and their encapsulation efficiencies were 76.90 +/- 0.84% and 81.08 +/- 0.85%, respectively. The pharmacokinetics experiments showed that the mean retention time (MRT) of rHV2 encapsulated in both kinds of micelles was significantly prolonged, especially for mPIC micelles. The confocal laser scanning microscopy intuitively proved the specific binding of RGD-PIC micelles to platelets. The efficacies of rHV2-loaded RGD-PIC micelles were greatly better than those of rHV2-loaded mPIC micelles and rHV2 solution in aspect of anticoagulation and inhibition of platelet aggregation. These results suggested platelet-targeting specificity of RGD-PIC micelles and that RGD-PIC micelles could potentially be used as a carrier for platelet-targeted delivery and long circulation of rHV2.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Xinru
authors.initials: X
authors.lastname: Li
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Zhou
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xingwei
authors.initials: X
authors.lastname: Chen
authors.forename: Jingxiong
authors.initials: J
authors.lastname: Yang
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Huang
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002412:Cations / Q000737:chemistry; D048271:Chitosan / Q000737:chemistry; D024764:Hirudin Therapy; D006629:Hirudins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000493:pharmacokinetics; D008297:Male; D008823:Micelles; D018613:Microscopy, Confocal; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry; D010974:Platelet Aggregation / Q000187:drug effects; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins
chemical_list: D000925:Anticoagulants; D002412:Cations; D006629:Hirudins; D008823:Micelles; D009842:Oligopeptides; D011108:Polymers; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid; C028210:monomethoxypolyethylene glycol; D048271:Chitosan