Liposomal drug delivery systems: from concept to clinical applications.

Production of large unilamellar vesicles by a rapid extrusion procedure. Characterization of size distribution, trapped volume and ability to maintain a membrane potential

https://dspace.library.uu.nl/bitstream/handle/1874/24866/cullis_79_Lipid%20polymorphism.pdf;sequence=1

Lipid polymorphism and the functional roles of lipids in biological membranes.

The results obtained in this study establish that liposome formulations incorporating a synthetic polyethylene glycol-derivatized phospholipid have a pronounced effect on liposome tissue distribution and can produce a large increase in the pharmacological efficacy of encapsulated antitumor drugs. This effect is substantially greater than that observed previously with conventional liposomes and is associated with a more than 5-fold prolongation of liposome circulation time in blood, a marked decrease in uptake by tissues such as liver and spleen, and a corresponding increased accumulation in implanted tumors. These and other properties described here have expanded considerably the prospects of liposomes as an effective carrier system for a variety of pharmacologically active macromolecules.

https://www.pnas.org/content/pnas/88/24/11460.full.pdf

Sterically stabilized liposomes: improvements in pharmacokinetics and antitumor therapeutic efficacy.

Small-volume extrusion apparatus for preparation of large, unilamellar vesicles

Preparation of liposomes of defined size distribution by extrusion through polycarbonate membranes

Preparation of unilamellar liposomes of intermediate size (0.1–0.2 μm) by a combination of reverse phase evaporation and extrusion through polycarbonate membranes

Characterization of liposomes prepared using a microemulsifier.

The folded conformation of the encephalitogenic protein of the human brain.

The membrane stabilization effect of cholesteryl hemisuccinate (CHEMS) and the sensitivity of the CHEMS-phosphatidylethanolamine membranes to protons and calcium ions were studied by differential scanning calorimetry, freeze-fracture electron microscopy, and 31P NMR. (1) At neutral pH, the addition of 8 mol % CHEMS to transesterified egg phosphatidylethanolamine (TPE) raised the lamellar-hexagonal transition temperature of TPE by 11 degrees C. Stable bilayer vesicles were formed when the incorporated CHEMS exceeded 20 mol %. (2) At a pH below 5.5, the protonation of CHEMS enhanced the formation of the hexagonal phase (HII) of TPE. At 25 mol % CHEMS the bilayer-hexagonal transition temperature was lowered by 30 degrees C at pH 4.5. (3) The endothermic acid-induced hexagonal hexagonal transition of TPE-CHEMS was suppressed at 35 mol % CHEMS. However, 31P NMR and electron microscopy indicated that a lamellar-hexagonal transition still occurred at this composition. (4) The main transition of TPE was not affected by the protonation of the incorporated CHEMS, indicating that no macroscopic phase separation occurred in TPE-CHEMS mixtures at low pH. (5) In contrast to the HII-promoting effect of H+, the neutralization of the negative charge on TPE-CHEMS by Ca2+ resulted in aggregates that remained in the lamellar structure even at the hexagonal transition temperature of TPE. It is suggested that calcium might form a complex between CHEMS in apposed bilayers. These results are related to the possible biological function of acidic cholesterol esters in biomembranes.

W.J. Vail

Papers

Preparation of liposomes of defined size distribution by extrusion through polycarbonate membranes

Preparation of unilamellar liposomes of intermediate size (0.1–0.2 μm) by a combination of reverse phase evaporation and extrusion through polycarbonate membranes

Characterization of liposomes prepared using a microemulsifier.

The folded conformation of the encephalitogenic protein of the human brain.

Acid- and calcium-induced structural changes in phosphatidylethanolamine membranes stabilized by cholesteryl hemisuccinate.