Synthesis of a novel polymer bile salts-(polyethylene glycol)2000-bile salts and its application to the liver-selective targeting of liposomal DDB.

Purpose: The objective of this study was to achieve a sustained and targeted delivery of liposome to the liver, by modifying the phospholipid [phosphatidylcholine (PC)/cholesterol (10 : 1) liposomes with a novel polymer bile salts-(polyethylene glycol)(2000)-bile salts (BP(2)B).

Methods: First, we generated a novel BP(2)B by N,N'-dicyclohexylcarbodiimide/4-dimethylaminopyridine esterification method and confirmed by Fourier transform infraredand (1) H-NMR spectra. Second, we prepared the BP(2)B-modified liposomes (BP(2)BL) that included BP(2)B, and the effect of the weight ratios of BP(2)B/PC on entrapment efficiency was investigated and BP(2)B/PC = 3% (w/w) was determined as the optimum ratio for the 4,4'-dimethoxy-5,6,5',6'-bi (methylenedioxy)-2,2'-bicarbomethoxybiphenyl liposomes. And then, the ability of the liver target of BP(2)BL was studied by calculating the targeted parameters.

Results And Discussion: All the results revealed that the introduction of polyoxyethylene chains could control interactions of bile salt moieties on liposome surfaces with the receptor compared with traditional liposomes (CL), marking BP(2)BL as a suitable carrier for hepatic parenchymal cell-specific and sustained targeting. It was suggested that liposomes containing such novel BP(2)B have great potential as drug delivery carriers for the liver-selective targeting that has targeted and sustained drug delivery.