Liposomes encapsulation

Liposomal encapsulation of DOX or DNR Preferred anthracycline delivery to the tumor Breast cancer, ovarian cancer, AIDS-related Kaposi s sarcoma, multiple myeloma (pegylated liposomal DOX). Breast cancer (uncoated liposomal DOX). AIDS-related Kaposi s sarcoma, acute mye-loblastic leukemia, multiple myeloma, non-Hodgkin s lymphomas (uncoated liposomal DNR)... 

A variety of other clinically important infections, such as brucellosis, listeriosis, salmonellosis, and various Mycobacterium infections, are of interest as these are often localized in organs rich in MPS cells. Liposome encapsulation has been demonstrated to improve therapeutic indices of several drugs in a number of infectious models. The natural avidity of macrophages for liposomes can also be exploited in the application of the vesicles as carriers of immunomodulators to activate these cells to an microbicidal, antiviral, or tumoricidal state. These studies were recently reviewed by Emmen and Storm (1987), Popescu et al. (1987), and Alving (1988). In addition to the treatment of "old" infectious diseases, the concept of MPS-directed drug delivery is of considerable interest for the therapy AIDS, possibly enabling control of human immunodeficiency virus replication in human macrophages. 

Encapsulation of cDDP in liposomes did not show such favorable effects. Liposome encapsulation of cDDP decreased the antitumor effect (Fig. 9). It was demonstrated that administration of cDDP liposomes resulted in a lower incidence as well as reduced severity of focal alterations of the epithelium of the proximal tubuli compared to administration of the free drug (Steerenberg et al., 1988). However, despite this reduction in renal toxicity the therapeutic index... 

FIGURE 9 Antitumor activity of liposome-encapsulated cDDP and free cDDP in solid IgM immunocytoma-bearing Lou/M rats. Tumorbearing rats were injected with 2 mg cDDP/kg body weight twice a week (arrow). Tumor diameter at the start of the experiment was 2-3 cm. Tumor growth during treatment is presented (mean SD of six animals unless otherwise indicated). Liposomes DPPC/DPPG/ chol (molar ratio 10 1 10) size about 0.7 pm. PC/PS/chol (molar... 

Delivery of peptides and proteins via the gastrointestinal tract has not been successful because of poor penetration through the intestinal epithelium and high levels of proteolytic activity in the gastrointestinal tract. Liposomal encapsulation of proteins and peptides will not improve the efficiency and capacity of this absorption pathway considerably (e.g., Ryman et al., 1982 Machy and Leserman, 1987 Weiner and Chia-Ming Chiang, 1988). These difficulties in delivery via the oral route caused the parenteral route to remain the preferred route for the administration of therapeutic peptides... 

In conclusion, until now insufficent data have been available to define general rules to predict for which drugs liposome encapsulation will be therapeutically beneficial when applied to the skin. It is too early to draw definite conclusions about the advantage of the vise of liposomes over alternative dermal delivery systems in the therapy for drugs designed to exert a pharmacological effect either locally or systemically. 

Prolonged presence of the drug at the site of injection is the aim of liposome encapsulation of drugs, which are injected in the vitreous body. Both amphotericin and gentamicin in liposome formulations were cleared from the injection site significantly more slowly than the free drug residence times depended on liposome size and, in some cases, on bilayer composition (Tremblay et al., 1985 Barza et al., 1985, 1987 Fishman et al., 1986). 

In conclusion, delivery of liposome-encapsulated drugs in eye drops can improve the extent of uptake and the residence time compared to the free drug. In particular, lipophilic substances seem to benefit from this approach. The exact mechanism behind the improved biopharmaceutical behavior still has to be unraveled. Intra-vitreal injection of drug-containing liposomes increases the residence times of both hydrophilic and lipophilic drugs. 

Presently, several clinical trials with liposome-encapsulated agents are under way and more are planned (Zonneveld and Crommelin, 1988 Klausner, 1988). During the last 5 years, key issues related to the pharmaceutical manufacturing of liposomes such as stability, sterilization, upscaling, and reproducibility have been successfully addressed. Although it is generally believed that a proper selection of the bi-layer components can minimize the occurrence of toxic effects due to the use of natural body constituents, the issue of liposome-related toxicity is not a trivial one and should be carefully studied,... 

Allen, T. M., and Everest, J. M. (1983). Effect of liposome size and di ug release properties on pharmacokinetics of liposome-encapsulated drugs in rats, J. Pharmacol. Exp. Ther.. 226, 539-544. 

Therapy of leishmaniasis Superior efficacies of liposome-encapsulated drugs, Proc. Natl. Acad. Sci. USA, 75, 2959-2963. 

Fishman, P. G., Peyman, G. A., and Lesar, T. (1986). Intra-vitreal liposome-encapsulated gentamicin in a rabbit model,... 

Hirano, K., and Hunt, C. A. (1985). Lymphatic transport of liposome-encapsulated agents Effects of liposome size following intraperitoneal administration, J. Pharm. Sci., 74, 915-921. 

Juliano, R. L., and Stamp, D. (1975). Effect of particle size and charge on the clearance rates of liposomes and liposome encapsulated drugs, Biochlm. Biophys. Res. Commun.. 63, 651-658. 

Juliano, R. L., and Me Cullough, H. N. (1980). Controlled delivery of an antitumor drug Localized action of liposome encapsulated cytosine arabinoside administered via the respiratory system, J. Pharmacol. Exp. Ther., 214, 381-387. 

D. (1978). Effect of lipid vesicle (liposome) encapsulation of methotrexate on its chemotherapeutic efficacy in solid rodent tumors. Cancer Res., 38, 2848-2853. 

Lautersztain, J., Perez-Soler, R., Khokhar, A. R., Newman, R. A., and Lopez-Berestein, G. (1986). Pharmacokinetics and tissue distribution of liposome-encapsulated cis-bis-N-decyUminodiacetato-... 

Lopez-Berestein, G., Metha, R., Hopfer, R. L., Mills, K., Kasi, L., Metha, K., Fainstein, V., Luna, M., Hersh, E. M., and Juliano, R. L. (1983). Treatment and prophylaxis of disseminated infection due to Candida albicans in mice with liposome-encapsulated amphotericin B, J. Infect. Pis.. 147, 939-945. 

Altered tissue distribution of amphotericin B by liposomal encapsulation Comparison of normal mice and mice infected with Candida albicans. Cancer Drug Deliv., 1, 199-205. 

E. M., and Juliano, R. L. (1984c). Liposome-encapsulated amphotericin B for treatment of disseminated candidiasis in neutropenic mice, J. Infect. Pis., 150, 278-283. 

M. (1987). Tumor targeting potential of liposomes encapsulating Ga-67 and antibody to Dalton s lymphoma associated antigen (anti-DLAA), Int. J. Rad. Oncol. Biol. Phys.. 13, 1713-1719. 

Wiebe, V. J., and Degregorio, M. W. (1988). Liposome-encapsulated amphotericin B A promising new treatment for disseminated fungal infections. Rev. Infect. Pis., 10. 1097-1101. 

Li, L., Braiteh, F.S., and Kurzrock, R., Liposome-encapsulated curcumin in vitro and in vivo effects on proliferation, Apopf. Signal. Angiogen. Cancer, 104, 1322, 2005. Socaciu, C., Jessel, R., and Diehl, H.A., Competitive carotenoid and cholesterol incorporation into liposomes effects on membrane phase transition, fluidity, polarity... 

Niwa, Y., Soniya, K., Michelson, A.M. and Puget, K. (1985). Effect of liposomal-encapsulated superoxide dismutase on active oxygen-related disorders. A preliminary study. Free Rad. Res. Commun. 1, 137-153. 

Nakae, D., Yoshiji, H., Amanuma, T., Kinugasa, T., Farber, J.L. andKonishi, Y. (1990). Endocytosis-independent uptake of liposome-encapsulated superoxide dismutase prevents the killing of cultured hepatocytes by tert-butyl hydroperoxide. Arch. Biochem. Biophys. 279, 315-319. 

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