Liposomes functional derivatives

Some 0-tosyl-lactones (e.g. 20 and 21) have been cyclized to tetrahydrofuran derivatives (22 and 23 respectively) on boiling in dioxane-water and synthesis of 2-deoxy-4-ep/-neuraminic acid and 2,4-dideoxy-neuraminic acid have been recorded. Liposomes functionalized with neuraminic acid by way of a C-... 

Fig. 11 Methods for the construction of PEGylated liposomes, (a) Liposomes possessing reactive groups, such as amino and carboxyl groups, can be prepared by incorporating lipophilic components containing these functional groups into a bilayer membrane. Functionalized liposomes can be PEGylated by reaction with activated PEG derivatives, (b) Preparation of PEGylated liposomes using PEG derivatives possessing lipid moieties...

Numerous methods have been developed for attaching ligands to the surface of liposomes for reviews, see Refs. (3,6 ). For peptides, they fall into two major categories (i) covalent coupling of the peptides to preformed liposomes that contain functionalized hydrophobic anchors such as, e.g., derivatives of phos-phatidylethanolamine (PE) or (ii) incorporation of lipopeptides, obtained by conjugation of peptides to hydrophobic anchors (fatty acids, phospholipids), into liposomes either during the preparation of the vesicles or by postinsertion into preformed vesicles. In this section, we will briefly discuss these techniques and focus on the ones we have been using in our own work. 

Similarly, the partitioning of nitroimidazoles into octanol-water, log Poet and into four liposome preparations with different lipid composition, log KM, was determined and regression equations were derived to explain the observed variation in the pharmacokinetic parameters of these drugs [85]. The log fCM ranged from 1.5 to 0.5 and was at least two- to threefold greater than log Poct (Table 4.24). In addition, the hydrophobic substituent constants of functional groups in various partitioning systems... 

Several pharmaceutical activities of nucleic acid analogs such as poly(VAd) have been studied in vitro and in cell-free systems [19]. It was expected that the present polymers would be effectively transferred into phagocytes by encapsulating in polysaccharide-coated liposomes and would show increased pharmaceutical activities similar to poly(maleic acid-a/l-2-cyclohexyl-l, 3-dioxap-5-ene) (MA-CDA) [68]. The activation of human neutrophils by poly(VAd) was evaluated by monitoring the in vitro superoxide anion production from activated human neutrophils. Shown in Table 15 is the superoxide liberated from human neutrophils (1 x 106 cells/ml) activated by poly(VAd) (0.5 mg/ml) as a function of time. Poly(VAd) encapsulated in mannan derivative-coated liposomes showed a... 

The higher generation dendrimeric derivative proved more effective in its interaction with liposomes. This behaviour was attributed to multivalent effects, exhibited at a greater extent by this dendrimeric derivative. Under an equal concentration of functional moieties the reactivity is favoured when the groups are located in a smaller number of particles. Thus the dendrimeric materials act as molecular glue causing adhesion of liposomal particles. 

The silatecan (DB-67) (21) represents a new generation of camptothecin derivatives (see Table 12) that exhibits a potent in vitro DNA topoisomerase I (TOPl)-mediated DNA-damaging activity, improved blood stability, and holds significant promise for the treatment of human cancers [79]. This new agent was found to be 25-times more lipophilic than camptothecin it incorporates readily into cellular and liposomal bilayers. In addition, its 10-hydroxy functionality enhances drug stability in the presence of human serum albumin. Thus, the net... 

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