Polysialic acid-modifying liposomes for efficient delivery of epirubicin, in-vitro characterization and in-vivo evaluation

•A new PSA derivative, polysialic acid-octadecyl dimethyl betaine conjugate (PSA-BS18), was synthesized.•PSA-BS18 modified epirubicin liposomes were successfully prepared and characterized.•PSA-BS18 is a suitable material to prolong the circulation time of the modified liposomes.•In vivo studies confirmed EPI-SL have enhanced tumor accumulation and improved antitumor efficacy.

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 ± 0.92 nm, a zeta potential of −26.23 ± 1.50 mV 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.

Graphical abstractDownload high-res image (114KB)Download full-size image