Repeated Administration of Hyaluronic Acid Coated Liposomes with Improved Pharmacokinetics and Reduced Immune Response.
PEGylated liposomes (PEG-Lip) have been widely used as a drug carrier for their good stealth property in blood circulation. However, the second injection of PEG-Lip was reported to result in the accelerated blood clearance (ABC) phenomenon and trigger hypersensitivity reactions in sensitive individuals for its complement activation effect. To avoid adverse immune responses, HA was selected to modify liposomes to afford HA modified liposomes (HA-Lip). Repeated administrations of PEG-Lip and HA-Lip were performed in rats. Our results showed that PEG-Lip induced the ABC phenomenon accompanied by a greatly increased accumulation of PEG-Lip in the liver. In contrast, HA-Lip showed good stealth property without inducing either the ABC phenomenon or an increase in liver uptake. Moreover, HA-Lip did not trigger complement activation in human serum in vitro and in rat blood in vivo. Consequently, HA modification represents a viable strategy to prolong the blood circulation time of liposomes without inducing the ABC phenomenon and adverse immune responses.
Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu 610041, China.|School of Pharmacy, Chengdu Medical College , Chengdu 610083, China.
Quan
Q
Zhang
Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu 610041, China.
Caifeng
C
Deng
Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu 610041, China.
Yao
Y
Fu
Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu 610041, China.
Xun
X
Sun
Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu 610041, China.
Tao
T
Gong
Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University , Chengdu 610041, China.
Zhirong
Z
Zhang
D000818:Animals; D003167:Complement Activation / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage; D005260:Female; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000276:immunology*; D007267:Injections / Q000379:methods; D008081:Liposomes / Q000008:administration & dosage* / Q000276:immunology*; D008099:Liver / Q000187:drug effects; D008297:Male; D008813:Mice, Inbred ICR; D011092:Polyethylene Glycols / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar
D004337:Drug Carriers; D008081:Liposomes; D011092:Polyethylene Glycols; D006820:Hyaluronic Acid
ABC phenomenon; complement activation; hyaluronic acid; liposomes