Design and synthesis of novel galactosylated polymers for liposomes as gene drug carriers targeting the hepatic asialoglycoprotein receptor.
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.
Wang
Si Ling
SL
Department of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
Yu
Feng Bo
FB
Jiang
Tong Ying
TY
Sun
Chang Shan
CS
Wang
Tianyi
T
Zhang
Jing Hai
JH
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
D037263:Asialoglycoprotein Receptor; D008081:Liposomes; D009838:Oligodeoxyribonucleotides; D011108:Polymers; D005690:Galactose