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

Plasma‐stable liposomes (100 nm) were prepared from dioleoylphosphatidylethanolamine (DOPE) and 3–6 mol% of a new disulfide‐linked poly(ethylene glycol)‐phospholipid conjugate (mPEG‐DTP‐DSPE). In contrast to similar preparations containing non‐cleavable PEG‐phospholipid conjugate, thiolytic cleavage of the grafted polymer chains facilitated rapid and complete release of the liposome contents. Furthermore, the detachment of PEG from DOPE liposomes resulted in liposomal fusion. Finally, while formulation of pH‐sensitive DOPE/cholesterol hemisuccinate liposomes with mPEG‐DTP‐DSPE abolished the pH sensitivity, cleavage of the PEG chains completely restored this property. These are the first examples of new useful properties of liposomes grafted with cleavable polymer.

[1]  L. Huang,et al.  Phosphatidylethanolamine liposomes: drug delivery, gene transfer and immunodiagnostic applications. , 1992, Biochimica et biophysica acta.

[2]  P. Cullis,et al.  Poly(ethylene glycol)--lipid conjugates regulate the calcium-induced fusion of liposomes composed of phosphatidylethanolamine and phosphatidylserine. , 1996, Biochemistry.

[3]  C. Gilon,et al.  Attachment of drugs to polyethylene glycols , 1983 .

[4]  A J Lomant,et al.  Chemical probes of extended biological structures: synthesis and properties of the cleavable protein cross-linking reagent [35S]dithiobis(succinimidyl propionate). , 1976, Journal of molecular biology.

[5]  M. Bally,et al.  Production of large unilamellar vesicles by a rapid extrusion procedure: characterization of size distribution, trapped volume and ability to maintain a membrane potential. , 1985, Biochimica et biophysica acta.

[6]  M S Newman,et al.  Long circulating, cationic liposomes containing amino‐PEG‐phosphatidylethanolamine , 1994, FEBS letters.

[7]  W. R. Morrison.  A FAST, SIMPLE AND RELIABLE METHOD FOR THE MICRODETERMINATION OF PHOSPHORUS IN BIOLOGICAL MATERIALS. , 1964, Analytical biochemistry.

[8]  L. Huang,et al.  Amphipathic poly(ethylene glycol) 5000-stabilized dioleoylphosphatidylethanolamine liposomes accumulate in spleen. , 1992, Biochimica et biophysica acta.

[9]  F. Szoka,et al.  Acid- and calcium-induced structural changes in phosphatidylethanolamine membranes stabilized by cholesteryl hemisuccinate. , 1985, Biochemistry.

[10]  L. Huang,et al.  Structural and functional comparisons of pH-sensitive liposomes composed of phosphatidylethanolamine and three different diacylsuccinylglycerols. , 1990, Biochimica et biophysica acta.

[11]  M. Woodle,et al.  Sterically stabilized liposomes. , 1992, Biochimica et biophysica acta.

[12]  P. Low,et al.  Folate-mediated tumor cell targeting of liposome-entrapped doxorubicin in vitro. , 1995, Biochimica et biophysica acta.

[13]  D. Friend,et al.  Proton-induced fusion of oleic acid-phosphatidylethanolamine liposomes. , 1985, Biochemistry.

[14]  D. Papahadjopoulos,et al.  Membrane contact, fusion, and hexagonal (HII) transitions in phosphatidylethanolamine liposomes. , 1986, Biochemistry.

[15]  F. Szoka,et al.  Preparation of liposomes of defined size distribution by extrusion through polycarbonate membranes. , 1979, Biochimica et biophysica acta.

[16]  J. Boggs.  Intermolecular hydrogen bonding between lipids: influence on organization and function of lipids in membranes. , 1980, Canadian journal of biochemistry.

[17]  S. Zalipsky.  Synthesis of an end-group functionalized polyethylene glycol-lipid conjugate for preparation of polymer-grafted liposomes. , 1993, Bioconjugate chemistry.

[18]  D. Papahadjopoulos,et al.  Endocytosis of liposomes by macrophages: binding, acidification and leakage of liposomes monitored by a new fluorescence assay. , 1990, Biochimica et biophysica acta.

[19]  T. Allen,et al.  A new strategy for attachment of antibodies to sterically stabilized liposomes resulting in efficient targeting to cancer cells. , 1995, Biochimica et biophysica acta.

[20]  F. Szoka,et al.  H+- and Ca2+-induced fusion and destabilization of liposomes. , 1985, Biochemistry.

[21]  P. Cullis,et al.  Poly(ethylene glycol)-lipid conjugates promote bilayer formation in mixtures of non-bilayer-forming lipids. , 1996, Biochemistry.