title: Design and synthesis of novel galactosylated polymers for liposomes as gene drug carriers targeting the hepatic asialoglycoprotein receptor.
abstract: The 18-mer oligodeoxynucleotides (ODNs) that can inhibit survivin gene expression were selected as a model gene drug to study hepatic-targeting drug delivery system. Novel galactosylated polymers (cholesteryloxycarbonylamino) ethylamine-alpha,beta-polyasparthydrazied (CHE-PAHy-Lacs), which target asialoglycoprotein receptor on hepatic parenchymal cells (PC), were designed and synthesized as non-toxic, non-antigenic and non-teratogenic ligands for liposomes. The liposomes incorporating different CHE-PAHy-Lacs were prepared and characterized by zeta potential and particle size analyzer. The drug encapsulation efficiency was measured by gel filtration method. 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate was used as a marker for all the liposome preparations in the in vivo experiments. The CHE-PAHy-Lac liposomes produced a significant improvement in the encapsulation efficiency of ODNs (28.73-51.37%) compared with conventional liposomes (9.88%). The in vivo results showed that the liposomes incorporating CHE-PAHy-Lac, which contained about 30% (w/w) galactosyl residues, exhibited marked accumulation in the liver and hepatic PC. These results suggest that the novel galactosylated polymers used for liposomes have a great potential as a gene delivery system for hepatic targeting.
authors: Department of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors: Si Ling
authors: SL
authors: Wang
authors: Feng Bo
authors: FB
authors: Yu
authors: Tong Ying
authors: TY
authors: Jiang
authors: Chang Shan
authors: CS
authors: Sun
authors: Tianyi
authors: T
authors: Wang
authors: Jing Hai
authors: JH
authors: Zhang
mesh_terms: D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000378:metabolism*; D005690:Galactose / Q000737:chemistry; D008081:Liposomes; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage*; D011108:Polymers / Q000008:administration & dosage* / Q000138:chemical synthesis; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D037263:Asialoglycoprotein Receptor; D008081:Liposomes; D009838:Oligodeoxyribonucleotides; D011108:Polymers; D005690:Galactose