Abstract: A synthetic lung surfactant composition and process for depositing a monolayer of a phosphatidylcholine lung surfactant to the alveoli of a mammal. The composition comprises a phosphatidylcholine lung surfactant, a phosphatidylethanolamine, and cholesterol in proportions such that the composition is in lamellar form at or below a first temperature and in non-lamellar form at a second temperature which is higher than the first temperature. A preferred phosphatidylcholine lung surfactant for use in this invention is dipalmitoyl phosphatidylcholine (DPPC), which is known to be the major lipid constituent of natural mammalian lung surfactant, and a preferred phosphatidylethanolamine is dioleoyl phosphatidylethanolamine (DOPE). In particular embodiments, the composition is in lamellar form at about room temperature (25.degree. C.), and in non-lamellar form at a temperature in the range of about 30.degree. to 37.degree. C., which is at or below normal human body temperature (37.degree. C.).

Abstract: Provided herein is a method of administering a liposome composition to an animal, the method involving adminstering to the animal a liposome composition containing an adverse physiological reaction-reducing effective amount of a liposome which has, in addition to a bioactive agent, a lipid bilayer containing a lipid and a surface agent-modified molecule. An adverse physiological reaction which may be experienced by the animal upon administration of a liposome composition is reduced by way of the presence of the surface agent-modified molecule in the liposome's lipid bilayer.

Abstract: This invention provides a taxane derivative of the formula: ##STR1## wherein a hydrophobic organic moiety is attached to a taxane. R and R.sup.1 is each indepently H or a hydrophobic organic moiety, as long as at least one of R and R.sup.1 is not H. Attachment of a hydrophobic organic moiety to the taxane so as to obtain a taxane derivative generally stabilizes the association of the derivative with a lipid, including a liposomal lipid, carrier in the plasma of animals to which the derivative-carrier association is administered. Also provided herein is a composition containing the taxane derivative and a pharmaceutically acceptable medium; desirably, the medium also contains a lipid carrier, and the derivative is associated with the carrier. Further provided herein is a method of administering taxane derivatives to animals, for example, animals afflicted with cancers.

Abstract: Dehydrated liposomes are prepared by drying liposome preparations under reduced pressure in the presence of one or more protective sugars, e.g., the disaccharides trehalose and sucrose. Preferably, the protective sugars are present at both the inside and outside surfaces of the liposome membranes. Freezing of the liposome preparation prior to dehydration is optional. Alternatively, the protective sugar can be omitted if: (1) the liposomes are of the type which have multiple lipid layers; (2) the dehydration is done without prior freezing; and (3) the dehydration is performed to an end point which results in sufficient water being left in the preparation (e.g., at least 12 moles water/mole lipid) so that the integrity of a substantial portion of the multiple lipid layers is retained upon rehydration.

Abstract: High ratio active agent:lipid complexes, their preparation and use are disclosed. Particular reference is made to cephalosporin:lipid complex and iodinated contrast agent:lipid complex. Use of high ratio cephalosporin:lipid complex in bacterial prophylaxis, and particularly bacteremia prophylaxis, including a method of preventing bacterial infection in an animal over an extended period comprising the step of administering to said animal a high ratio cephalosporin:lipid complex is further disclosed as is the use of high ratio iodinated contrast agent:lipid complex in X-ray applications.

Abstract: Aminoglycosides, analogs and derivatives thereof, in the form of phosphate salts are described as well as the process for making and utilizing same. Aminoglycoside phosphate liposomes and nonguanadino aminoglycoside phosphate liposomes, their preparation and use, are particularly described.

Abstract: A method for making a pharmaceutical composition is described. The composition is comprised of an organic acid derivative of alpha tocopherol, and may additionally comprise other lipids. The composition may be in the form of liposomes, and as such are associated with or entrap a bioactive agent. Particularly suited for such systems are drugs stable at acidic pH, for example drugs having imidazole groups, such as pilocarpine. The composition requires a stabilizer to maintain the bilayer phase of the organic acid derivative of alpha tocopherol in a low pH environment. Such a stabilizer is for example a detergent. Upon in vivo administration of the system and concomitant increase of pH, viscosity of the preparation increases.

Abstract: Methods and compositions are described for the preparation of alpha-tocopherol vesicles, the bilayers of which comprise a salt form of an organic acid derivative of alpha-tocopherol such as the Tris salt form of alpha-tocopherol hemisuccinate. The method is rapid and efficient and does not require the use of organic solvents. The alpha-tocopherol vesicles may be used to entrap compounds which are insoluble in aqueous solutions. Such preparations are especially useful for entrapping bioactive agents of limited solubility, thus enabling administration in vivo.

Abstract: Methods and compositions are described for the preparation of bioactive agents entrapped in lipid vesicles the bilayers of which comprise a salt form of an organic acid derivative of a sterol, such as the tris-salt form of a sterol hemisuccinate, and to compositions comprising a mixture of tris(hydroxymethyl)aminomethane salt of cholesteryl hemisuccinate with either an antifungal compound or a peptide. These compositions have various applications in vivo.

Abstract: Methods and compositions are described for the preparation of alpha-tocopherol vesicles, the bilayers of which comprise a salt form of an organic acid derivative of alpha-tocopherol such as the Tris salt form of alpha-tocopherol hemisuccinate. The method is rapid and efficient and does not require the use of organic solvents. The alpha-tocopherol vesicles may be used to entrap compounds which are insoluble in aqueous solutions. Such preparations are especially useful for entrapping bioactive agents of limited solubility, thus enabling administration in vivo.

Abstract: Methods and compositions are described for the preparation of bioactive agents entrapped in lipid vesicles the bilayers of which comprise a salt form of an organic acid derivative of a sterol, such as the tris-salt form of a sterol hemisuccinate, and to bompositions comprising a mixture of tris(hydroxymethyl)aminomethane salt of cholesteryl hemisuccinate with either an antifungal compound or a peptide. These compositions have various applications in vivo.

Abstract: A new and substantially improved type of lipid vesicle, called stable plurilamellar vesicles (SPLVs), are described, as well as the process for making the same and X-ray diffraction methods for identifying the same. SPLVs are characterized by lipid bilayers enclosing aqueous compartments containing one or more entrapped solutes, the concentration of such solutes in each aqueous compartment being substantially equal to the emunization of solutes used to prepare the SPLVs. The bilayers of SPLVs are substantially non-compressed. SPLVs are stable during storage and can be used in vivo for the sustained release of compounds and in the treatment of disease.

Abstract: A pharmacological agent-lipid solution preparation comprising a lipophilic pharmacological agent, a desalted charged lipid and an aqueous-miscible lipid solvent such that upon introduction into an aqueous medium a suspension of lipid aggregates associated with the pharmacological agent are formed, and methods of manufacture and use.

Abstract: Preparations of drugs in admixture with certain ligands are described which, when administered to animals or humans, are less toxic than conventional drug preparations. Although the toxicity of the drug-ligand preparations described is greatly reduced, the drug retains pharmacological activity.

Abstract: Methods and compositions are described for the preparation of alpha-tocopherol vesicles, the bilayers of which comprise a salt form of an organic acid derivative of alpha-tocopherol such as the Tris salt form of alpha-tocopherol hemisuccinate. The method is rapid and efficient and does not require the use of organic solvents. The alpha-tocopherol vesicles may be used to entrap compounds which are insoluble in aqueous solutions. Such preparations are especially useful for entrapping bioactive agents of limited solubility, thus enabling administration in vivo.

Abstract: A new and substantially improved type of lipid vesicle, called stable plurilamellar vesicles (SPLVs), are described, as well as the process for making the same and X-ray diffraction methods for identifying the same. SPLVs are characterized by lipid bilayers enclosing aqueous compartments containing one or more entrapped solutes, the concentration of such solutes in each aqueous compartment being substantially equal to the concentration of solutes used to prepare the SPLVs. The bilayers of SPLVs are substantially non-compressed. SPLVs are stable during storage and can be used in vivo for the sustained release of compounds and in the treatment of disease.

Abstract: A multilamellar vesicle dispersed in an aqueous phase comprising an aqueous medium, a lipid concentration of at least about 50 mg/ml and a trapping efficiency of at least about 40 percent. The vesicle can be prepared by dispersing the lipid in an aqueous phase to form a multilamellar vesicle, rapidly freezing the multilamellar vesicle to obtain a frozen lipid-aqueous medium mixture, and warming the mixture to obtain a frozen and thawed multilamellar vesicle dispersed in an aqueous phase.

Abstract: A method and composition are described for the solubilization of hydrophobic materials using a lysophospholipid. The method includes drying a composition comprising a hydrophobic material-solubilizing effective amount of phospholipid from organic solvent and hydrating the resulting film with an aqueous medium at either a pH of between about 8.5 and about 14.0, or at pH 7.0 followed by reduction of the temperature to less then 0.degree. C.

Abstract: Preparations of drugs in admixture with certain ligands are described which, when administered to animals or humans, are less toxic than conventional drug preparations. Although the toxicity of the drug-ligand preparations described is greatly reduced, the drug retains pharmacological activity.

Abstract: Steroidal liposomes comprising a bioactive agent and method for their administration are disclosed, the bilayers of said steroidal liposomes comprising a salt form of a carboxylic acid derivative of a sterol, a salt form of a polycarboxylic acid derivative of a sterol, a salt form of a hydroxy carboxylic acid derivative of a sterol, a salt form of an amino acid derivative of a sterol or a salt form of a poly (amino acid) derivative of a sterol; or a salt form of an organic acid derivative of cholesterol, a vitamin D, a phytosterol, or a steroidal hormone.