title: Polyethylene glycol-complexed cationic liposome for enhanced cellular uptake and anticancer activity.
abstract: Liposomes as one of the efficient drug carriers have some shortcomings such as their relatively short blood circulation time, fast clearance from human body by reticuloendothelial system (RES) and limited intracellular uptake to target cells. In this study, polyethylene glycol (PEG)-complexed cationic liposomes (PCL) were prepared by ionic complex of cationically charged liposomes with carboxylated polyethylene glycol (mPEG-COOH). The cationic liposomes had approximately 98.6+/-1.0 nm of mean particle diameter and 45.5+/-1.1 mV of zeta potential value. While, the PCL had 110.1+/-1.2 nm of mean particle diameter and 18.4+/-0.8 mV of zeta potential value as a result of the ionic complex of mPEG-COOH with cationic liposomes. Loading efficiency of model drug, doxorubicin, into cationic liposomes or PCL was about 96.0+/-0.7%. Results of intracellular uptake evaluated by flow cytometry and fluorescence microscopy studies showed higher intracellular uptake of PCL than that of Doxil. In addition, in vitro cytotoxicity of PCL was comparable to cationic liposomes. In pharmacokinetic study in rats, PCL showed slightly lower plasma level of DOX than that of Doxil. In vivo antitumor activity of DOX-loaded PCL was comparable to that of Doxil against human SKOV-3 ovarian adenocarcinoma xenograft rat model. Consequently, the PCL, of which surface was complexed with PEG by ionic complex may be applicable as drug delivery carriers for increasing therapeutic efficacy of anticancer drugs.
authors: Biomaterials Research Center, Korea Research Institute of Chemical Technology, Yuseong, Deajeon, Republic of Korea; Center for Bioactive Molecular Hybrids and Department of Chemistry, Yonsei University, Seoul, Republic of Korea.
authors: Suk Hyun
authors: SH
authors: Jung
authors: Soon Hwa
authors: SH
authors: Jung
authors: Hasoo
authors: H
authors: Seong
authors: Sun Hang
authors: SH
authors: Cho
authors: Kyu-Sung
authors: KS
authors: Jeong
authors: Byung Cheol
authors: BC
authors: Shin
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001692:Biological Transport; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D004337:Drug Carriers; D004339:Drug Compounding; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007275:Injections, Intravenous; D008081:Liposomes; D009682:Magnetic Resonance Spectroscopy; D008546:Melanoma, Experimental / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; D011092:Polyethylene Glycols; D004317:Doxorubicin