Liposomal drug delivery systems: from concept to clinical applications.

There are many potential barriers to the effective delivery of a drug in its active form to solid tumors. Most small-molecule chemotherapeutic agents have a large volume of distribution on i.v. administration ([Speth et al., 1988][1]; [Chabner and Longo, 1996][2]). The result of this is often a

Optimizing Liposomes for Delivery of Chemotherapeutic Agents to Solid Tumors

Dermaseptin, a 34 amino-acid residue antimicrobial polypeptide [Mor, A., Nguyen, V. H., Delfour, A., Migliore-Samour, D., & Nicolas, P. (1991) Biochemistry 30, 8824-8830] was synthesized and selectively labeled at its N-terminal amino acid with either 7-nitrobenz-2-oxa-1,3-diazole-4-yl (NBD), rhodamine, or fluorescein. The fluorescent emission spectra of the NBD-labeled dermaseptin displayed a blue-shift upon binding to small unilamellar vesicles (SUV), reflecting the relocation of the fluorescent probe to an environment of increased apolarity. Titrations of solutions containing NBD-labeled dermaseptin with SUV composed of zwitterionic or acidic phospholipids were used to generate binding isotherms, from which were derived surface partition constants of (0.66 +/- 0.06) x 10(4) M-1 and (2.8 +/- 0.3) x 10(4) M-1, respectively. The shape of the binding isotherms, as well as fluorescence energy transfer measurements, suggests that some aggregation of membrane-bound peptide monomers occurs in acidic but not in zwitterionic vesicles. The preferential susceptibility of the peptide to proteolysis when bound to zwitterionic but not to acidic SUV suggests that these aggregates might then penetrate a relatively short distance into the hydrophobic region of the acidic membrane. Furthermore, the results provide good correlation between the peptide's strong binding and its ability to permeate membranes composed of acidic phospholipids, as revealed by a dissipation of diffusion potential and a release of entrapped calcein from SUV.

Interaction of antimicrobial dermaseptin and its fluorescently labeled analogues with phospholipid membranes.

Liposomes, spherical bilayer vesicles from dispersion of polar lipids in aqueous solvents, have been widely studied for their ability to act as drug delivery vehicles by shielding reactive or sensitive compounds prior to release. Liposome entrapment has been shown to stabilize encapsulated, bioactive materials against a range of environmental and chemical changes, including enzymatic and chemical modification, as well as buffering against extreme pH, temperature, and ionic strength changes. Liposomes have been especially useful to researchers in studies of various physiological processes as models of biological membranes in both eukaryotes and prokaryotes. Industrial applications include encapsulation of pharmaceuticals and therapeutics, cosmetics, anti-cancer and gene therapy drugs. In the food industry, liposomes have been used to deliver food flavors and nutrients and more recently have been investigated for their ability to incorporate food antimicrobials that could aid in the protection of food products against growth of spoilage and pathogenic microorganisms. In this review we briefly introduce key physicochemical properties of liposomes and review competing methods for liposome production. A survey of non-agricultural and food applications of liposomes are given. Finally, a detailed up-to-date summary of the emerging usage of liposomes in the food industry as delivery vehicles of nutrients, nutraceuticals, food additives, and food antimicrobials is provided.

L.G. Cleland

Papers

Serum-induced leakage of liposome contents.