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Polysialylated Liposomes: Preparation, Characterization and Stability Studies In Vitro and In Vivo

Zhang, Xiaoqin; (1999) Polysialylated Liposomes: Preparation, Characterization and Stability Studies In Vitro and In Vivo. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

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.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Polysialylated Liposomes: Preparation, Characterization and Stability Studies In Vitro and In Vivo
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
URI: https://discovery.ucl.ac.uk/id/eprint/10110853
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