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Modulation of cell membrane disruption by pH-responsive pseudo-peptides through grafting with hydrophilic side chains

R. Chen, Z. Yue, M. E. Eccleston, S. Williams and N.K.H. Slater, Journal of Controlled Release, 2005, 108(1), 63-72

The effect of grafting an amphiphilic pseudo-peptide, poly (l-lysine iso-phthalamide), with poly (ethylene glycol) or a hydrophilic poly (ethylene glycol) analogue, Jeffamine M-1000®, on the pH-dependent erythrolytic activity and in vitro cytotoxicity have been studied together with the concentration-dependent haemolysis of the polymers with different degrees of grafting. PEGylated polymers showed pH-dependent membrane-disruptive ability similar to the parent poly (l-lysine iso-phthalamide). The polymers showed a better ability to haemolyse the erythrocyte membrane at mildly acidic pHs with increasing degree of PEGylation (up to 17.0 wt.%). Further increasing the degree of PEGylation resulted in a decrease in haemolytic ability. Grafting poly (l-lysine iso-phthalamide) with the lower molecular weight Jeffamine M-1000® had little effect on the haemolytic ability. Finally, the in vitro cytotoxicity of the grafted polymers was assessed by MTT assay, LDH assay and viable cell counts. At pH 7.4, these polymers were well tolerated by a range of mammalian cell lines and grafting reduced the cytotoxicity of polymers. However, at pH 5.5, relative to poly (l-lysine iso-phthalamide), the grafted polymers displayed a better ability to rupture the outer membranes of these cells.


Category: BioScience Engineering group, Cambridge | Added by: drug-delivery (04.10.2010)
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Molecular Simulation group, Tarragona [4]
Theory of Polymers at Interfaces group, Dresden [1]
BioScience Engineering group, Cambridge [2]
Membrane Biophysics Group, Copenhagen [0]
Membranes and Microforces Mcube group, Strasbourg [0]
Biological Physics group, Manchester [0]
Biomedical and Health Research Centre, Leeds [0]
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