title: Polysialic acid-modifying liposomes for efficient delivery of epirubicin, in-vitro characterization and in-vivo evaluation.
abstract: Polysialic acid (PSA) serves as a hydrophilic polymer and affords conjugated biologically active molecules a longer circulation time in vivo. Furthermore, PSA could potentially target tumor tissues and help achieve better curative effects. In this study, PSA was conjugated with octadecyl dimethyl betaine (BS18) to yield a PSA-BS18 conjugate. The PSA-BS18 modified liposomal epirubicin (EPI-SL), had a particle size of 133.63±0.92nm, a zeta potential of -26.23±1.50mV and an encapsulation efficiency (%EE) of 96.23±1.16%. In vitro release studies showed that PSA-BS18 could delay EPI release from the modified liposomes. The MTT assay suggested that EPI-SL led to stronger cytotoxic activity than that exhibited by common and PEGylated liposomes. The pharmacokinetic study showed that EPI-SL prolonged the residence time of the EPI in the blood compared with that observed from common liposomes. Bio-distribution results obtained from tumor-bearing mice clearly demonstrated that PSA-BS18 increased the accumulation of modified liposomes in tumors compared with that of common liposomes. In the antitumor efficacy study, EPI-SL showed the best antitumor and life-prolonging effects among all of the tested formulations. These findings strongly indicate EPI-SL might have great potential as an effective approach for anticancer therapy.
authors: College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors: Ting
authors: T
authors: Zhang
authors: College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors: Songlei
authors: S
authors: Zhou
authors: College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors: Ling
authors: L
authors: Hu
authors: College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors: Bo
authors: B
authors: Peng
authors: College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors: Yang
authors: Y
authors: Liu
authors: College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors: Xiang
authors: X
authors: Luo
authors: College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors: Yanzhi
authors: Y
authors: Song
authors: College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
authors: Xinrong
authors: X
authors: Liu
authors: College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China. Electronic address: pharmdeng@gmail.com.
authors: Yihui
authors: Y
authors: Deng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D015251:Epirubicin / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D051379:Mice; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012794:Sialic Acids / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D012794:Sialic Acids; C021319:polysialic acid; D011092:Polyethylene Glycols; D015251:Epirubicin
keywords: Antitumor efficacy; Long circulation time; Polysialic acid; Tumor shed