Super-hydrophilic zwitterionic poly(carboxybetaine) and amphiphilic non-ionic poly(ethylene glycol) for stealth nanoparticles

Nonionic polyethylene glycol (PEG) as a stealth polymer destabilizes liposomes due to its amphiphilic property. As a result, PEGylated liposomes have to be further stabilized, such as by using a large amount cholesterol. This is a long existing dilemma faced by PEG. In this work, we show that zwitterionic poly(carboxybetaine) (PCB) stabilizes liposomes because of its superhydrophilic nature, thus solving this dilemma. Specifically, PCB-modified liposomes without cholesterol exhibited good retention of hydrophilic drug and long blood circulating characteristics in vivo. To further validate this new PCB chemistry, PCB liposomal doxorubicin without cholesterol was compared with DOXIL for their antitumor therapeutic efficacies.

Superhydrophilic zwitterionic polymers stabilize liposomes.

Effect of membrane composition on lipid oxidation in liposomes.

Binding and relaxation behaviour of prodan and patman in phospholipid vesicles: a fluorescence and 1H NMR study

In view of the many roles played by cholesterol in membranes, it is not surprising that the interactions of cholesterol with phospholipids, and their consequences with respect to membrane structure and function, have been studied intensively for more than three decades This chapter reviews recent studies on the importance of the isooctyl side chain of cholesterol on ordering of the acyl chains, as well as how variations in the alkyl side chain length affect the conformational order of fatty acyl chains of phospholipids in bilayer membranes and the molecular packing of phospholipids in monolayers The discussion focuses on recent biophysical studies of liposomes and monolayers in which the alkyl chain length of the sterol and/or the acyl chain length of the phospholipid were varied The results are interpreted according to the hydrophobic mismatch effect Also reviewed in this chapter are some recent kinetic studies of intermembrane movement and intracellular transport of sterols having a side-chain structure different from that of cholesterol For a recent review of other aspects of sterol-phospholipid interactions, including a more detailed discussion of the use of NMR spectroscopy to establish phase diagrams than are presented here, and an overview of differential interaction of cholesterol with subclasses of phospholipids, the reader is referred to Keough et al (1996) and reference cited therein

J. Higinbotham

Papers

DSC of DMPC liposomes containing low concentrations of cholesteryl esters or cholesterol

13C-NMR determination of the molecular dynamics of cholesterol in dimyristoylphosphatidylcholine vesicles

Cooperative unit and enthalpy studies of cholesterol and cholesteryl esters in dimyristoylphosphatidylcholine liposomes.