This invention pertains to pharmaceutical formulations which comprise (i) a
drug (e.g., an amphiphilic
drug) (e.g., an
anthracycline) (e.g.,
doxorubicin) and (ii) a short-chain
sphingolipid (e.g., a short-chain
glycosphingolipid or a short-chain
sphingomyelin) (e.g., N-octanoyl-glucosylceramide, referred to as C8-GlcCer) (e.g., N-hexanoyl-
sphingomyelin, referred to herein as C6-SM), and which provide improved
drug delivery and
efficacy. The short-chain sphingolipidis selected from compounds of the following formula: wherein: R1 is independently: an O-linked saccharide group; or an O-linked polyhydric
alcohol group; or: R1 is independently: an O-linked (optionally N-(C1-4
alkyl)-substituted amino)-C1-6
alkyl-
phosphate group; or an O-linked (polyhydric
alcohol-substituted)-C1-6
alkyl-
phosphate group; R2 is independently C3-9alkyl, and is independently unsubstituted or substituted; R3 is independently C7-19alkyl, and is independently unsubstituted or substituted; R4 is independently —H, —OH, or —O—C1-4alkyl; RN is independently —H or C1-4alkyl; the bond marked with an alpha (α) is independently a
single bond or a
double bond; if the bond marked with an alpha (α) is a
double bond, then R5 is —H; if the bond marked with an alpha (α) is a
single bond, then R5 is —H or —OH; the
carbon atom marked (*) is independently in an R-configuration or an S-configuration; the
carbon atom marked (**) is independently in an R-configuration or an S-configuration; and pharmaceutically acceptable salts, solvates, esters, ethers, chemically protected forms thereof. In one embodiment, the
pharmaceutical formulation is a liposomal
pharmaceutical formulation prepared using a mixture of lipids comprising, at least,
vesicle-forming lipids (e.g., phospholipids) (e.g., phosphatidylcholines) (e.g., fully hydrogenated soy
phosphatidylcholine (HSPC)) (e.g., dipalmitoyl-
phosphatidylcholine (DPPC)) and said short-chain
sphingolipid, and optionally
cholesterol and optionally a
vesicle-forming lipid which is derivatized with a
polymer chain (e.g., a
phosphatidylethanolamine (PE) which is derivatized with polyethyleneglycol (PEG)) (e.g., N-(carbonyl-
methoxypolyethylene glycol 2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine
sodium salt (MPEG2000-DSPE). The present invention also pertains to methods for the preparation and use of such formulations.