Untitled

Abstract

The intracellular processing of pH-sensitive liposomes composed of cholesterylhemisuccinate (CHEMS) and dioleoylphosphatidylethanolamine (DOPE) by eukaryotic cell lines has been compared to non-pH-sensitive liposomes made of CHEMS and dioleoylphosphatidylcholine (DOPC). The pH-sensitive liposomes can deliver encapsulated fluorescent molecules [calcein, fluoresceinated dextran, fluoresceinated polypeptide, and diphtheria toxin A chain (DTA)] into the cytoplasm. Cytoplasmic delivery can be blocked in the presence of ammonium chloride or EDTA, indicating that the process requires a low-pH environment and the presence of divalent cations. Inhibition of cellular protein synthesis by DTA delivery from the pH-sensitive liposome is orders of magnitude greater than from the non-pH-sensitive liposome composition. The delivery of DTA into the cytoplasm by pH-sensitive liposomes is at least 0.01% of cell-associated liposomal DTA. There is no significant difference in the degradation rate of bovine serum albumin (BSA) or the rate of acidification of pH-sensitive dye, 8-hydroxy-1,3,6-pyrene-trisulfonate (HPTS), when delivered to cells in pH-sensitive and non-pH-sensitive liposomes. Thus the efficiency of cytoplasmic delivery is less than 10% of the cell-associated liposome contents, which is the smallest difference that can be detected by these two assays. Based upon the various assays used to measure liposome content disposition in the cell, we conclude that the efficiency of cytoplasmic delivery by the CHEMS/DOPE liposomes is greater than 0.01% and less than 10% of the cell-associated liposomal contents.

Liposomes with detachable polymer coating: destabilization and fusion of dioleoylphosphatidylethanolamine vesicles triggered by cleavage of surface‐grafted poly(ethylene glycol)

“…pH-sensitive liposomes were prepared from DOPE and CHEMS (4:1 molar ratio) [15,16]. Lipid films were hydrated in HEPES-NS or HPTS-DPX solution (30 mM HPTS, 30 mM DPX, pH 7.2, adjusted to 290 mOs with NaCI) and extruded through two 0.1 gm polycarbonate membranes [17,18].…”

“…When pH drops to levels suppressing ionization of the amphiphile's carboxyl, the lipid undergoes phase transition with concomitant release of liposomal contents. Such pH-sensitive liposomes are potentially promising as carriers specific to the acidic environment of endosomes and many tumors [15,16,22,23,29,30]. Yet their potential use in vivo is hampered by their fast clearance by RES.…”

Docetaxel-loaded liposomes: preparation, pH sensitivity, Pharmacokinetics, and tissue distribution

“…Negatively charged lipids such as OA distributed among PE molecules provide electrostatic repulsions which decrease PE intermolecular interactions, thus preventing interbilayer interactions under physiological conditions (Connor and Huang, 1985;Straubinger et al, 1985;Chu et al, 1990). The protonation of OA in the acidic endosomal compartment neutralizes their negative charges, and the vesicles become destabilized as the PE component reverts to hexagonal II (HII) phase.…”

Tumor Cell Killing Enabled by Listeriolysin O-liposome-mediated Delivery of the Protein Toxin Gelonin

“…LLO and gelonin versus gelonin alone in pH-sensitive liposomes led us to test the hypothesis that LLO is able to significantly enhance the efficiency of delivering macromolecules even when used in combination with pH-insensitive liposomes (27,34). To test this hypothesis B16 cells were treated with LLO and gelonin co-encapsulated in liposomes consisting of either PE:CHEMS (pH-sensitive) or PC:CHEMS (pH-insensitive) for 1, 8, or 24 h and their metabolic activity monitored by the XTT assay (Fig.…”