Ceramide liposome

Fig. 2. Agarose gel electrophoresis of apoptotic DNA ladder formed by the incubation of cells with ceramide STPP liposomes. The cells were incubated with the various liposomal preparations for 18 h at a ceramide concentration equivalent to 25 pM, followed by DNA extraction and gel electrophoresis. Lane a ceramide liposomes lane b ceramide STPP liposomes lanec untreated...

Mice are randomized and liposomes injected IV via tail vein injection. The injection schedule followed is as per a previous study conducted using ceramide liposomes (10), with mice injected at a frequency of one injection per 2 days. 

Ferrying of molecules into cells via entry through caveolae may represent a way to traffic specifically cytotoxic molecules to specific action sites. For example, elevating the intracellular level of the sphingolipid ceramide is known to exert antimitogenic and proapoptotic effects. While ceramide is cell-permeable and displays antiapoptotic properties in vitro, systemic in vivo use of ceramide is hampered by its hydrophobicity. Using a C6-ceramide formulation in pegylated liposomes was shown to elicit a sixfold reduction in solid phase tumors, when compared to unloaded liposomes in a mouse model of breast adenocarcinoma [68],... 

T. C. Stover, A. Sharma, G. P. Robertson, and M. Kester. Systemic delivery of liposomal short-chain ceramide limits solid tumor growth in murine models of breast adenocarcinoma. Clin. Cancer Res. 11 3465-3474 (2005). 

Talk about milking a story. The newspapers got all excited when pop star Shania Twain revealed that the secret behind her soft, supple skin wasn t some complex, highly touted product filled with liposomes, collagen, or ceramides. The secret, she said, was udderly simple Bag Balm delivered the goods. Just as it had done for cow udders since 1908, when a small Vermont company decided to take the bull by the horns and tackle the chronic problem of chapped cow udders. 

Lipid moieties coupled to polyethylene glycol (PEG) have been used to increase the blood circulation time of lipoplexes (Fig. 32). The PEG-lipid conjugates such as DOPE-PEG, Chol-PEG, ceramides-PEG and their derivatives are then coformulated with the cationic lipid, helper lipid, and DNA. This results in coating the surface of the lipoplexes with PEG and preventing undesired association with plasma proteins or circulating cells (stealth liposomes). Recently, a-tocopheryl PEG-succinate (TPGS) was also used in gene delivery formulations because of its ability to confer not only a stealth property but also antioxidant and absorption enhancer properties [129]. 

Another group of naturally occurring lipids with applications in liposome technology is comprised of the sphingophospholipids (mainly sphingomyelin) which are derivatives of ceramides [17]. Sphingomyelin (SM) is found in the outer leaflet of plasma membranes [17] and has many similarities with PC since they both have the same zwitterionic polar group and two hydrophobic acyl chains. 

FIGURE 13 Blood and tumor concentrations of bioactive ceramide-lipid C6 in tumorbearing mice were maintained over a 48-h period (a) 10- and 40-mg/kg doses of liposomal-C6 followed first-order kinetics with blood concentration exceeding in vitro IC50 sustaibed at 48h (b) at these doses steady-state concentration of C6 in tumor tissue achieved at 60min. The 40-mg/kg dose maintained a concentration above the desired IC50 up to 48 h. (Reprinted from ref. 431 with permission of American Association for Cancer Research.)... 

Liposomes with compositions that imitate the skin s lipid content (ceramides, cholesterol, fatty acids, cholesterol sulfate) have also been prepared [37] and their pharmacological response on a skin barrier disruption model was assessed. Apart from their action as lipidic carriers for the repair of skin barrier, tliese liposomes are expected to penetrate easily the skin barrier due to their biocompatibilily with the stratum corneum. Many attempts have being made to incorporate ceramides, the major component of stratum corneum. These lipids have a relatively large stereochemical shape, and in the presence of water they tend to form multilamellar bilayers [50-53],... 

An interesting example of intracellular targeting of liposomes was described recently, when liposomes containing in their membrane composition mitochonriotropic amphiphilic cation with delocalized positive charge were shown to specifically target mitochondria in inact cells (153). The liposomes were deemed mitochondriotropic due to inclusion of lipidic analogues of triphenylphosphonium cations, which facilitates the efficient subcellular delivery of proapototic ceramide to mitochondria of mammalian cells and improves its activity in vitro and in vivo (154). 

BoddapatiSV etal (2008) Organelle-targeted nanocarriers Specific delivery of liposomal ceramide to mitochondria enhances its cytotoxicity in vitro and in vivo. Nano Lett 8 2559-2563... 

Drug-incorporated STPP liposomes are prepared by adding 10 mole% ceramide C6 to the lipid composition mentioned in step 1 in Subheading 3.1 earlier. 

Ceramide-incorporated STPP liposomes are evaluated for efficacy of targeted delivery by measuring cell cytotoxicity and DNA fragmentation. 

The cells are washed with serum free DMEM and liposomes diluted to the appropriate ceramide concentration, using serum-free DMEM. 

Cells are incubated with liposomes at a ceramide concentration of 25 pM for a time period of 18 h. 

STPP liposomes for tumor growth inhibition studies containing ceramide and 3 mole% PEG5000PE are prepared as described in Subheading 3.4 earlier. 

Shabbits JA, Mayer LD (2003) Intracellular delivery of ceramide lipids via liposomes enhances apoptosis in vitro. Biochim Biophys Acta 1612 98-106... 

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