Liposomes using

Subcutaneous injection of insulin encapsulated in liposomes in rats resulted in prolonged hypoglycemic effects compared to a solution of free insulin this study also indicated that a substantial fraction of hand-shaken multilamellar vesicles could enter the circulation in intact form after subcutaneous injection (Stevenson et al., 1982). The neutral liposomes used in this study were cleared more slowly from the injection site than the negatively charged liposomes. 

For a number of liposome preparations—both injectables and locally administered products—the therapeutic advantages over existing formulations have been proven in animal models clinical trials with liposome preparations are now under way. So far, clinical studies showed no significant toxic effects which could be ascribed to the lipid components of the liposomes used. 

Herbette and co-workers [425-428,445] studied the structures of drugs bound to liposomes using a low-angle X-ray diffraction technique. Although the structural... 

FIGURE 14.4 Rate of decay of 02 against (3-CRYP concentration in air-saturated solutions of DPPC unilamellar liposomes using either RB or PBA as ()2 sensitizer. 

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...

Figure 22.21 Antibodies may be conjugated to liposomes using an indirect approach incorporating a (strept)avidin-biotin system. Biotinylated liposomes may be complexed with biotinylated antibodies using (strept)avidin as a bridging molecule or may be complexed with an antibody-(strept)avidin conjugate.

Goundalkar, A., Chose, T., and Mezei, M. (1983) Covalent binding of antibodies to liposomes using a novel lipid derivative. /. Bharm. Pharmacol. 36, 465-466. 

Jopski B, Pirkl V, Jaroni HW, et al. Preparation of hemoglobin-containing liposomes using octyl glucoside and octyltetraoxyethylene. Biochim Biophys Acta 1989 978 79. 

Abugo 00, Balagopalakrishna C, Rifkind JM, et al. Direct measurements of hemoglobin interactions with liposomes using EPR spectroscopy. Artif Cells Blood Substit Immobil Biotechnol 2001 29 5. 

Figure 1 Chemical structures of some amphipathic weak bases that have been loaded and stabilized in liposomes using trialkylammonium salts of polyanionic trapping agents in our lab. (A) Doxorubicin, (B) epirubicin, (C) vinorelbine, (D) vincristine, (E) vinblastine, (E) topotecan, (G) irinotecan, (H) swainsonine, (I) 2-diethylami-noethyl-ellipticinium, (J) 6-(3-aminopropyl)ellipticine, and (K) LAQ824.

One method for the labeling of liposomes with chelator, hexamethylpropyleneamine oxime (HMPAO) was developed by Phillips et al. (16). Lipophilic HMPAO enters the liposome where it interacts with glutathione and becomes converted to the hydrophilic form, which is trapped in the liposome. A detailed protocol for radiolabeling liposomes using Tc-HMPAO has been reported (3). In a typical experiment, 10 to 15mCi (370-555 MBq) of Tc in the form of sodium pertechnetate... 

Gabizon A, Huberty J, Straubinger RM, Price DC, Papahadjopoulos D. An improved method for in vivo tracing and imaging of liposomes using a gallium 67-deferoxamine complex. J Liposome Res 1988 1 123. 

Cationic lipids cannot be dissolved in water and form aggregates in aqueous solution, such as bilayers. To prepare a homogeneous reagent, in most cases liposomes were made from cationic lipids in a first step. When it is not possible to form stable lipid bilayers (i.e., liposomes) using a single lipid, then it may be necessary to combine the cationic lipid with one or more so-called helper lipids like cholesterol (Choi) (41) or 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE) (42). 

Straubinger RM, Papahadjopoulos D, Hong KL. Endocytosis and intracellular fate of liposomes using pyranine as a probe. Biochemistry 1990 29(20) 4929-4939. 

Practically all available iodinated extracellular X-ray contrast agents have been encapsulated into liposomes using different lipids and methods of preparation. Table 1 gives a short and intentionally incomplete overview of some of the approaches. The first liposomal contrast agent preparation that was tested in humans contained diatrizoate [48]. The injected dose was up to 0.5 ml kg k The preparation was effective even in plain radiography where lesions down to 0.8-1.0 cm could be detected in patients. However, adverse events such as fever and hyperthermia, which occurred in 30% of the patients, limited further use. We have incorporated iopromide into MLVs that were prepared from phosphatidyl choline (PC), cholesterol and stearic acid at a molar ratio of 4 5 1 using the ethanol-evaporation technique [44]. The liposomes can be stored freeze-dried and they are reconstituted before use by... 

The oxidation of can proceed with hydroperoxides at a convenient rate without a catalyst, if the solution is heated to 90 °C, measuring at 348 nm. A modification of the iodometric method was proposed for determination of hydroperoxides in liposomes, using anhydrous EtOH as solvent in all the operations. A sample of liposome suspension is evaporated to dryness in a vacuum, after adding EtOH in a 4 96 sample-to-solvent proportion. 

Polyelectrolytes have recently found application in the development of pH sensitive liposomal controlled release systems. This application arises from the fact that polyelectrolytes may be used both to stabilize liposomes, and to disrupt liposomes in a pH dependent manner. Although the use of liposomes in oral pharmaceutical compositions has been discussed [424], liposomes generally suffer from poor stability and are therefore prone to leakage of the entrapped active agents. To overcome this problem, several authors have stabilized the liposomes using polyelectrolytes. For example, Tirrell and coworkers have employed ionene [425], and polyethylene imine) [426] to stabilize liposomes. Similarly, Sato and coworkers have studied maleic acid copolymers [427], and Sumamoto and coworkers have studied liposomes [428] coated with polysaccharides. In related work, Kondo and coworkers have emphasized the use of carboxymethyl chitin to produce artificial red blood cells [429-435]. 

Not only will the charge of a lipid and the composition of lipids affect the delivery of biomacromolecules, but the size of the liposome may alter the transport. Mixtures of insulin with three different diameter (1.98 pm, 0.4 pm, and 0.1 pm) neutral liposomes (DPPC Choi) resulted in similar overall hypoglycemic effects to insulin alone. Contrary to this finding is the fact that pulmonary absorption of liposomal [3H] terbutaline, a small molecule, has been reported to be dependent on both composition and size of the liposomes used (Abra et al. 1990). Differences in the absorption mechanism may be the explanation for this contradictory evidence further studies are needed to clarify this and other uncertainties about the uptake mechanism of macromolecules (Patton 1996). 

Figure 4. Patterns of enzyme release from liposomes using...

Figure 10.15 Plot of log 1 /LCi50 for guppies versus (a) log octanol-water distribution ratio (log Z),ow, Eq. 10-41), and (b) log liposome-water distribution ratio (log Z),lipsw, Eq. 10-41) at pH 7 for a series of chlorinated benzenes (o) and chlorinated phenols ( ) as well as for the herbicide 2-.9ec-butyl-4.6-dinitrophenol (dinoseb) (v). The liposomes used were L-a-dimy-ristoyl-phosphatidylcholine (chlorinated benzenes) and L-a-dioleyl-phosphatidylcholine (chlorinated phenols and dinoseb). The pH dependence of D/ow and D,lipsw of pentachlorophenol (PCP) and dinoseb is shown in Fig. 10.14. Data from Saarikoski and Viluskela (1992), Gobas et al. (1988), Escher and Schwarzenbach (1996), and Gunatilleka and Poole (1999).

Huang et al. (1980) coupled monoclonal antibodies to liposomes using an NHS ester modification of palmitic acid incorporated into the bilayer construction (Lapidot et al ... 

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