Multivesicular liposomes

While most vesicles are formed from double-tail amphiphiles such as lipids, they can also be made from some single chain fatty acids [73], surfactant-cosurfactant mixtures [71], and bola (two-headed) amphiphiles [74]. In addition to the more common spherical shells, tubular vesicles have been observed in DMPC-alcohol mixtures [70]. Polymerizable lipids allow photo- or chemical polymerization that can sometimes stabilize the vesicle [65] however, the structural change in the bilayer on polymerization can cause giant vesicles to bud into smaller shells [76]. Multivesicular liposomes are collections of hundreds of bilayer enclosed water-filled compartments that are suitable for localized drug delivery [77]. The structures of these water-in-water vesicles resemble those of foams (see Section XIV-7) with the polyhedral structure persisting down to molecular dimensions as shown in Fig. XV-11. 

Multivesicular Liposomes Kim and his colleages described a method for the preparation of cell size liposomes with high encapsulation efficiency the so-called multivesicular liposomes (Kim et al., 1983). The lipid phase consists of a combination of amphiphatic lipids and a small amount of triglycerides (triolein or trioctanoin) dissolved in chloroform-diethyl ether (1 1). The aqueous phase is slowly added to the organic phase and after vigorous shaking a water-ip-lipid emulsion is formed (Fig. 2A-B). Via a narrow Pasteur pipet the emulsion is subsequently added to a sucrose solution. 

Several studies have been performed in order to investigate the effect of liposomal size (Hirano and Hunt, 1985), lipid composition (Senior and Gregoriadis, 1982 Hirano et al., 1985), and lipid dose (Ellens et al., 1983, Kim et al., 1987) on the fate of liposomes after intraperitoneal administration. In the size range studied (0.048-0.72 Min), no size-dependent absorption could be expected (Hirano and Hunt, 1985). Particles larger than 22.5 pm are not expected to enter the lymphatic capillaries (Allen, 1956). After intraperitoneal administration of multivesicular liposomes (19 + 7 ym), Kim and Howell (1987a) and Kim et al. (1987) showed that liposomal entrapment of Ara-C prolongs the half-Ufe of the drug in the peritoneal... 

Kim, S., and Howell, S. B. (1987a). Multivesicular liposomes containing cytarabine entrapped in the presence of hydrochloric acid for intracavitary chemotherapy. Cancer Treatm. Rep., 71. 705-711. 

Liposomes consist of many phospholipid bilayers of only few, or just one bilayer (Fig. 5). Therefore multilamellar vesicles (MLV), oligolamellar vesicles (OLV), small unilamellar (SUV), and large unilamellar vesicles (LUV) have to be distinguished. Furthermore, multivesicular liposomes (MVL) may be formed. 

Jain, S. K., Jain, R. K., Chourasia, M. K., Jain, A. K., Chalasani, K. B., Soni, V., and Jain, A. (2005). Design and development of multivesicular liposomal deopt delivery system for controlled systemic delivery of acyclovir sodiumAAPS Pharm. Sci. Tech., 6, E35-E40. 

Liposomes (see Section 5.3.1), even small unilamellar vesicles, are usually too large to cross the BBB. Multivesicular liposomes of the order of 0.3-2 wm in diameter are retained by brain following systemic administration however, this is due to embolization of these large structures within the brain microvasculature. Since 40-80 nm liposomes do not undergo significant transport through the BBB, it is expected that nanoparticles, which typically have diameters of 140-300 nm, would also have insignificant... 

Katre, N.V. Asherman, J. Schaefer, H. Multivesicular liposome (DepoFoam ) technology for the sustained delivery of insulin-like growth factor-I. J. Pharm. Sci. 1998, 7(11), 1341-1346. 

Matsuo H, Chevallier I, Mayran N, et al. (2004) Role of LBPA and Alix in multivesicular liposome formation and endosome organization. Science 303 531-534... 

Zhong H, Deng Y, Wang X, Yang B. Multivesicular liposome formulation for the sustained delivery of breviscapine. Int J Pharm. 2005 301(l-2) 15-24. 

DepoDur is a sterile, non-pyrogenic, white to olf-white, preservative-free suspension of multi-vesicular lipid-based particles containing morphine sulfate, USP. The lipid carrier is a proprietary drug delivery system known as DepoFoam . After the administration of DepoDur into the epidural space, morphine sulfate is released from the multivesicular liposomes over a period of time [1-3] (Figures 44.2 and 44.3). 

Morphologically, with respect to the vesicle size and number of lamellae, it is possible to distinguish between small (S), large (L), and giant (G) uni-, oligo-, or multilamellar [U, O, ML, respectively] vesicles [Vj. Combination of these letters, 0[] ], gives rise to several widely used abbreviations for various vesicles, such as SUV, LUV, LOV, GOV, and MLV In the case when the encapsulated vesicles are not concentric, multivesicular liposomes are defined (MVL). Similar structure characterizes also DepoFoam, which consists of ca. 10 pm suspended particles with multiple interior compartments made of bifincated lipid bilayers. Structurally, they... 

On the basis of their size and their number of lipid bilayers, liposomes are classified into multilamellar vesicles (MLVs, diameter >200 nm), large unilamellar vesicles (diameter 100-1000 nm) and small xmilamellar vesicles (diameter <100 nm) (Fig. 28.2). However, other structures have also been described. For example, DepoCyte , a liposomal formulation of the anti-cancer drug cytara-bine, can be described as a multivesicular liposome (Fig. 28.3). 

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