tamine ethylenediamine derivatives (bromphenifamine, diphenhydramine ); Anti-protozoa!: quinolones (iodoquinol); amidines (pentamidine ); antihelmintics (pyrantel); anti› schistosomal drugs ( oxaminiquine ); antifungal triazole derivatives (fliconazole, itraconazole, ketoconazole, micon› azole ); antimicrobial cephalosporins ( cefazolin, cefonicid, cefotaxime, ceftazimide, cefuoxime); antimicrobial beta› lactam derivatives (aztreopam, cefmetazole, cefoxitin); anti› microbials of erythromycine group ( erythromycin, azithro› mycin, clarithromycin, oleandomycin); penicillins (benzylpenicillin, phenoxymethylpenicillin, cloxacillin, methicillin, nafcillin, oxacillin, carbenicillin); tetracyclines; other antimicrobial antibiotics, novobiocin, spectinomycin, vancomycin; antimycobacterial drugs: aminosalicycic acid, capreomycin, ethambutol, isoniazid, pyrazinamide, rifabu› tin, rifampin, clofazime; antiviral adamantanes: amantadine, rimantadine; quinidine derivatives: chloroquine, hydroxy› chloroquine, promaquine, qionone; antimicrobial qionolo› nes: ciprofloxacin, enoxacin, lomefloxacin, nalidixic acid, norfloxacin, ofloxacin; sulfonamides; urinary tract antimi› crobials: methenamine, nitrofurantoin, trimetoprim; nitroimidazoles: metronidazole; cholinergic quaternary ammonium compounds (ambethinium, neostigmine, phys› ostigmine); anti-Alzheimer aminoacridines (tacrine); anti› Parkinsonal drugs (benztropine, biperiden, procyclidine, tri› hexylhenidyl); anti-muscanmc agents (atropine, hyoscyamine, scopolamine, propantheline ); adrenergic dop› amines (albuterol, dobutamine, ephedrine, epinephrine, nor› epinephrine, isoproterenol, metaproperenol, salmetrol, terb› utaline ); ergotamine derivatives; myorelaxants or curane series; central action myorelaxants; baclophen, cycloben› zepine, dentrolene; nicotine; beta-adrenoblockers (acebutil, amiodarone ); benzodiazepines ( ditiazem); antiarrhythmic drugs ( diisopyramide, encaidine, local anesthetic series› procaine, procainamide, lidocaine, flecaimide ), quinidine; ACE inhibitors: captopril, enelaprilat, fosinoprol, quinapril, ramipril; antilipidemics: fluvastatin, gemfibrosil, HMG-coA inhibitors (pravastatin); hypotensive drugs: clonidine, gua› nabenz, prazocin, guanethidine, granadril, hydralazine; and non-coronary vasodilators: dipyridamole. 

According to the present invention, the entity contained in the liposome composition of the present invention can also be a pre-entity, e.g., a pro-drug or an agent that is capable of being converted to a desired entity upon one or more conversion steps under a condition such as a change in pH or an enzymatic cleavage of a labile bond. Such conversion may occur after the release of the pro-drug from the lipo› some interior at the intended site of the drug/liposome action. However, the pre-entity can be converted into the desired active entity inside the liposomes of the present invention prior to the use of the liposomes as a delivery vehicle, e.g., administration to a patient. For example, an entity can be modified into a pre-entity so that it is easier to be loaded into the liposomes and then it can be converted back into the desired entity once it is inside the liposomes of the present invention. In this manner, according to the present invention, the entities that are generally not ame› nable to "active", "remote" or other gradient-based loading methods, can be effectively loaded into liposomes, e.g., into the liposome interior space, in their native, unmodified form. 

Globally cationic compounds, that is, compounds capable of attaining a net positive ionic charge under the liposome loading conditions, especially the compounds containing a titratable amine, are known to effectively load into lipo› somes exhibiting transmembrane ion gradients. If an entity of interest is an organic compound and is not a globally cationic compound having a titratable amine, a derivative 

thereof having the requisite ionic properties can be prepared by a suitable modification, e.g., according to the methods described in Woodle et al., in WO 96/25147. For example, an amine group can be introduced by esterification of a hydroxyl group of the entity with an amino acid. Alterna› tively, a hydrophobic group can be introduced into a water› soluble compound to aid in its partition into the liposome membrane and subsequent traversing of the membrane to the intraliposomal compartment, i.e., inside the liposomes. Another useful modification to create a liposome-loadable pre-entity is the formation of a carbonyl group adduct, e.g., a hydrazone, an oxime, an acetal, or a ketal. A modified amino-containing group can be hydrolyzed or otherwise chemically split from the modified compound after the loading of the modified compound into the liposomes according to the present invention. Typical processes to intraliposomally regenerate the entity from a pre-entity are hydrolysis, photolysis, radiolysis, thiolysis, ammonolysis, reduction, substitution, oxidation, or elimination. These pro- cesses can be effected, without limitation, by the change of pH or by an enzymatic action. For example, paclitaxel or docetaxel, a non-ionic entities, are converted into their 2’-( diethylaminopropionyl)- or T-( diethylaminopropionyl) esters, which are weak bases (pre-entities). After loading into the liposomes by any known method, including, without limitation, "active", "remote", "transmembrane-gradient› based" or "solubility gradient based" methods, and/or the methods of the present invention, the intraliposomal 2’› ( diethylaminopropionyl)-paclitaxel is converted into origi- nal paclitaxel by stimulating its hydrolysis through the increase of pH to above pH 7 .0. Thus, a liposome encapsu› lating a neutral taxane molecule within its interior space is obtained with the drug/lipid ratio of over 0.05 mole per mole of the liposome lipid, without the help of hydrophilic covalent modifications of the taxane molecule ( e.g. by attachment of PEG), cyclodextrine taxane complexes, or taxane-solubilizing, micelle-forming surfactants. 

According to the present invention, the liposomes con› tained in the liposome composition of the present invention can be any liposome known or later discovered in the art. In general, the liposomes of the present invention can have any liposome structure, e.g., structures having an inner space sequestered from the outer medium by one or more lipid bilayers, or any microcapsule that has a semi-permeable membrane with a lipophilic central part where the mem› brane sequesters an interior. A lipid bilayer can be any arrangement of amphiphilic molecules characterized by a hydrophilic part (hydrophilic moiety) and a hydrophobic part (hydrophobic moiety). Usually amphiphilic molecules in a bilayer are arranged into two dimensional sheets in which hydrophobic moieties are oriented inward the sheet while hydrophilic moieties are oriented outward. Amphiphi› lic molecules forming the liposomes of the present invention can be any known or later discovered amphiphilic mol- ecules, e.g., lipids of synthetic or natural origin or biocom› patible lipids. Liposomes of the present invention can also be formed by amphiphilic polymers and surfactants, e.g., polymerosomes and niosomes. For the purpose of this disclosure, without limitation, these liposome-forming materials also are referred to as "lipids". 

According to the present invention, the liposomes con› tained in the liposome composition of the present invention can also be targeting liposomes, e.g., liposomes containing one or more targeting moieties or biodistribution modifiers on the surface of the liposomes. A targeting moiety can be any agent that is capable of specifically binding or interact› ing with a desired target. In one embodiment, a targeting 

