Liposome entrapment

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... 

Begent, R. H. J., Green, A. J., Bagshawe, K. D., Jones, B. E., Keep, P. A., Searle, F., Jewkes, R. F., Barrat, G. M., and Ryman, B. E. (1982). Liposomally entrapped second antibody improves tumor imaging with radiolabelled (first) antitumor anti-body. Lancet, 2, 739-742. 

Jackson, A. J. (1981). Intramuscular absorption and regional lymphatic uptake of liposome-entrapped inulin. Drug Metab. Dispos., 9, 535-540. 

Mayhew, E., and Rustum, Y. (1983). Effect of liposome entrapped chemotherapeutic agents on mouse primary and metastatic tumors, Biol. Cell. 81-85. 

Parker, R. J., Hartman, K. D., and Sieber, S. M. (1981b). Lymphatic absorbtion and tissue disposition of liposome-entrapped [1 CJadriamycin following intraperitoneal administration, Cancer Res., 41, 1311-1317. 

Rhalem, A., Bourdieu, C., Luffau, G., and Pery, P. (1988). Vaccination of mice with liposome-entrapped adult antigens of Nippo-strongylus brasiliensis. Ann. Inst. Pasteur/Immunol.. 139, 157-166. 

Rustum, Y. M., Chandrakant, D., Mayhew, E., and Papahadjopoulos, D. (1979). Role of liposome t5 e and route of administration in the antitumor activity of liposome-entrapped l-p-arabinofuranosyl-cytosine against mouse L1210 leukemia. Cancer Res.. 39, 1390-1395. 

Imaizumi, S., Woolworth, V., Fishman, R.A. and Chan, P.H. (1990). Liposome-entrapped superoxide dismutase reduces infarction in cerebral ischemia in rats. Stroke 21, 1312-1317. 

Freeman, B.A., Turrens, J.F., Mirza, Z., Crapo, J.D. and Young, S.L. (1985). Modulation of oxidant lung injury by using liposome-entrapped superoxide dismutase and catalase. Fed. Proc. 44, 2591-2595. 

Gregoriadis, G., and Neerunjun, D.E., Control of the rate of hepatic uptake and catabolism of liposome-entrapped proteins injected into rats possible therapeutic applications, European Journal of Biochemistry, 1974, 47, 179-185. 

J. P. O Connell, R. L. Campbell, B. M. Fleming, T. J. Mercolino, M. D. Johnson, and D. A. McLaurin, A highly sensitive immunoassay system involving antibody-coated tubes and liposome-entrapped dye, clin. Chem. 31, 1424-1426 (1985). 

Entrapment of plasmid DNA and/or protein into liposomes entails the preparation of a lipid film from which multilamellar vesicles and, eventually, small unilamellar vesicles (SUVs) are produced. SUVs are then mixed with the plasmid DNA and/or protein destined for entrapment and dehydrated. The dry cake is subsequently broken up and rehydrated to generate multilamellar dehydration-rehydration vesicles (DRV) containing the plasmid DNA and/or protein. On centrifugation, liposome-entrapped vaccines are separated from nonentrapped materials. When required, the DRV are reduced in size by microfluidization in the presence or absence of nonentrapped materials or by employing an alternative method (7) of DRV production, which utilizes sucrose (see below). 

It can therefore be concluded that immunization with liposomes containing both DNA and the encoded antigen leads to superior immune responses when compared with liposomes entrapping the DNA or protein vaccine alone. 

Perrie Y, Gregoriadis G. Liposome-entrapped plasmid DNA characterization studies. Biochim Biophys Acta 2000 1475 125-132. 

Cardile, V., Renis, M., Gentile, B., and Panico, A.M., Activity of liposome-entrapped immunomodulator oligopeptides on human epithelial thymic cells, Pharm. Pharmacol. Commun., 6, 381-386, 2000. 

Ramundo-Orlando, A., Mattia, E, Palombo, A., and D Inzeo, G. (2000). Effect of low frequency, low amplitude magnetic fields on the permeability of cationic liposomes entrapping carbonic anhydrase, part II. Bioelectromagnetics, 21,499-507. 

A very recent development is encapsulation of actives in colloidosomes [16, 41]. The method is analogous to liposome entrapment. Selectively permeable capsules are formed by surface-tension-driven deposition of solid colloidal particles onto the surface of an inner phase or active ingredient in a water-in-oil or an oil-in-water emulsion composed of colloidal particles. Initially synthetic polymer microparticles were used but more recently a natural alternative has been described based on small starch particles. After spray-drying, redispersible emulsions can be formed. 

Liposomes were formed from 1,2-dipalmitoylphosphatidylcholine (DPPC) and cholesterol (Choi) and the effect of liposomal entrapment on pulmonary absorption of insulin was related to oligomerization of insulin (Liu et al. 1993). Instillation of both dimeric and hexameric insulin produced equivalent duration of hypoglycemic response. However, the initial response from the hexameric form was slightly slower than that from dimeric insulin, probably due to lower permeability across alveolar epithelium of the hexameric form caused by larger molecular size. The intratracheal administration of liposomal insulin enhanced pulmonary absorption and resulted in an absolute bioavailability of 30.3%. Nevertheless, a similar extent of absorption and hypoglycemic effects was obtained from a physical mixture of insulin and blank liposomes and from liposomal insulin. This suggests a specific interaction of the phospholipid with the surfactant layer or even with the alveolar membrane. 

When the microencapsulated liposomes are left untreated the lipid bilayer provides a barrier to diffusion through which the entrapped protein does not pass until the liposomes gradually become leaky, primarily due to oxidation of the phospholipid side chains. This mechanism results in a delayed release. Triton or sonic treatment of the microencapsulated liposomes provide pulsed re ease. Since both detergent and sonication disrupt lipid bi ayers, the mechanism by which pulsed release is achieved may be that these stimuli initially disrupt the liposomes and then the lipid reforms around some of the protein solution inside the capsule, possibly in an altered lamellar form alternatively, the treatment could disrupt only the more susceptible liposomes, leading to two phases of release, first from the freed protein and later from protein that remained liposome-entrapped. 

Nicolau, C., Le Pape, A., Soriano, P., Fargette, F. and Juhel, M.F. (1983) In vivo expression of rat insulin after intravenous administration of the liposome-entrapped gene for rat insulin I. Proc. Natl. Acad. Sci. USA, 80, 1068-1072. 

Lee, R. J., and Low, P. S. Folate-mediated tumor cell targeting of liposome-entrapped doxorubicin in vitro. Biochim. Biophys. Acta 1233 134-44, 1995. 

NTA has found new applications in the medical sciences liposomally entrapped luIn-NTA has been screened for potential in detection of tumours in mice84 and ferric NTA has been used to stimulate in vivo lipid peroxidation. 

The high hydrophilicity and corresponding low lipophilicity of both EDTA and DTP A result in very low uptake of these chelating agents into cells. In an endeavour to increase intracellular uptake of DTPA, Rahman et al.98 injected liposomally entrapped DTP A into mice which had hepatic accumulations of 239Pu. Although this was an effective treatment for mice it proved to be unsatisfactory for hamsters99. ... 

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