title: Two cholesterol derivative-based PEGylated liposomes as drug delivery system, study on pharmacokinetics and drug delivery to retina.
abstract: In this study, two cholesterol derivatives, (4-cholesterocarbonyl-4'-(N,N,N-triethylamine butyloxyl bromide) azobenzene (CAB) and 4-cholesterocarbonyl-4'-(N,N-diethylamine butyloxyl) azobenzene (ACB), one of which is positively charged while the other is neutral, were synthesized and incorporated with phospholipids and cholesterol to form doxorubicin (DOX)-loaded liposomes. PEGylation was achieved by including 1,2-distearoyl-sn-glycero-3-phosphatiylethanol-amine-N-[methoxy-(polyethylene glycol)-2000 (DSPE-PEG2000). Our results showed that PEGylated liposomes displayed significantly improved stability and the drug leakage was decreased compared to the non-PEGylated ones in vitro. The in vivo study with rats also revealed that the pharmacokinetics and circulation half-life of DOX were significantly improved when liposomes were PEGylated (p < 0.05). In particular, the neutral cholesterol derivative ACB played some role in improving liposomes' stability in systemic circulation compared to the conventional PC liposome and the positively charged CAB liposome, with or without PEGylation. In addition, in the case of local drug delivery, the positively charged PEG-liposome not only delivered much more of the drug into the rats' retinas (p < 0.001), but also maintained much longer drug retention time compared to the neutral PEGylated liposomes.
authors: School of Biomedical Engineering, Shanghai Jiaotong University, Shanghai, 200240, People's Republic of China.
authors: Shengyong
authors: S
authors: Geng
authors: Bin
authors: B
authors: Yang
authors: Guowu
authors: G
authors: Wang
authors: Geng
authors: G
authors: Qin
authors: Satoshi
authors: S
authors: Wada
authors: Jin-Ye
authors: JY
authors: Wang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D002784:Cholesterol / Q000031:analogs & derivatives / Q000138:chemical synthesis; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D008081:Liposomes / Q000737:chemistry / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects*
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D002784:Cholesterol