Abstract
Poly (ethylene glycol) (PEG) modified nanocarriers are being used widely in the drug delivery system (DDS). However, the “accelerated blood clearance (ABC) phenomenon” was induced upon repeated administration of PEG-modified liposomes, resulting in reduced blood circulation time, and increased accumulation in liver and spleen. To avoid the unexpected phenomenon, polysialic acid (PSA) was selected to modify liposomes. PSA is a natural, highly hydrophilic polysaccharide polymer for which no receptors exists in the body. It is non-immunogenic, biodegradable and endows the conjugated bioactive macromolecule and drugs with increased circulation time in vivo. In the present study, the in vivo evaluation showed that PSA modified liposomes (PSA-Lip) afford extended blood circulation in wistar rats and beagle dogs. Moreover, the ABC phenomenon did not occur and the IgM antibody was not induced after repeated injections of PSA-Lip. These results strongly suggest that PSA modification represents a promising strategy to afford good stealth of the liposomes without evoking the ABC phenomenon.
Highlights
It is well known that common nanocarriers are recognized by the mononuclear phagocyte system (MPS), and are rapidly cleared from the blood circulation, distributed in the liver and spleen, which affect the effectiveness
A classic method based on the Gouy–Chapman theory was used to measure the fixed hydration layer thickness (FALT) of common liposomes (CLip), Polyethylene glycol (PEG)-Lip and polysialic acid (PSA)-Lip [34,35]. 10, 50, 100, 150, and 200 mM NaCl solutions were prepared
The results showed that PSA modified liposomes (PSA-Lip) could afford extended blood circulation time in time in vivo
Summary
It is well known that common nanocarriers are recognized by the mononuclear phagocyte system (MPS), and are rapidly cleared from the blood circulation, distributed in the liver and spleen, which affect the effectiveness. PEGylation technology can reduce the recognition of drugs/carriers by MPS and prolong blood circulation time, thereby using the enhanced permeability and retention (EPR) effect to achieve disease sites targeting [3,4]. If the PEGylated liposomes encapsulated cytotoxicity drug, the ABC phenomenon would causes serious toxic effects due to the accumulation in MPS in liver and spleen [16]. In vivo antitumor studies revealed that PSA-PEG modified liposomal epirubicin, serving as a binding molecule to the tumor site, exhibited increased accumulation in tumor area, enhanced the antitumor activity with reduced systemic toxicity. Luo et al [30] synthesized a PSA-p-octadecylamine conjugate (PSA-p-ODA) and decorate it on the surface of liposomal pixantrone, Experimental results showed that the modification of PSA-p-ODA could prolong the circulation time of the liposomal pixantrone, and targeted to peripheral blood neutrophils, which provide a neutrophil-mediated drug delivery system for the eradication of tumors. The systemic study was conducted to investigate whether PSA-Lip would overcome the ABC phenomenon and complement activation after intravenous administrations
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
