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Title: Polysialylated liposomes : preparation, characterization and stability studies in vitro and in vivo
Author: Zhang, Xiaoqin
ISNI:       0000 0001 3577 3693
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 1999
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Colominic acid (CA), a derivative of polysialic acid B, with molecular weight at 15,000- 18,000 and sialic acid (SA) were incorporated into liposomes for reducing the uptake of liposomes by reticuloendothelial system (RES) and enhancing the half-life of liposomes in the circulation. Colominic acid was initially coupled with phosphatidylethanolamine (PE) by the Schiff reaction to form a linear polymer (PE- OX-CA), and the yield of PE-OX-CA was approximately 22.8-34.1 % depending on the reaction conditions. Conjugation of PE with CA in the presence of carbodiimide catalysts led to the formation of branched polymers (PE-CA). However, PE-OX-CA was difficult to be incorporated into lipid bilayers. Inclusion of PE-CA into liposomes composed of PC and equimolar cholesterol achieved 12.2-39.0%. Further animal results showed that the half-life of liposomes containing PE-CA did not improve significantly. The conjugation of colominic acid with the liposome surface (polysialylated liposomes) by the Schiff reaction was conducted. Results showed that the remaining of polysialylated liposomes (PC/Chol/PE 1:1.2:0.2, molar ratio) in the mouse circulation was improved to two-fold compared with native liposomes (PC/Chol/PE 1:1.2:0.2, molar ratio). The stability of polysialylated liposomes incubated in human serum albumin and mouse plasma was much better than native liposomes, and the surface charge of polysialylated liposomes was around -7.1mV to - 11.1mV. Sialic acid coupled with PE (PE-SA) was incorporated into liposomes composed of PC and equimolar cholesterol. The half-life of PE-SA-containing liposomes in the mouse blood circulation was improved. In conclusion, polysialic acid stabilized liposomes and delayed the clearance of liposomes from the circulation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Stealth; Anticancer