Drugs liposome encapsulation

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. 

The fate of injected liposomes is drastically altered by administration route, dose and size, lipid composition, surface modification, and encapsulated drugs. Liposomes encapsulating drugs are often administered iv, therefore, the stability of liposomes in plasma is important. When liposomes composed of PC with unsaturated fatty acyl chains are incubated in the presence of serum, an efflux of internal solute from the liposomes is observed. This increase in permeability is caused by the transfer of phospholipids to high density lipoprotein (HDL) in serum (55). To reduce the efflux of liposomal contents, cholesterol is added as a liposomal component... 

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... 

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. 

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. 

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. 

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. 

A challenge in designing liposome systems is the assessment of drug release from such systems in vitro. Use of agarose gel matrices has been reported as one approach to evaluate the release kinetics of liposome-encapsulated materials in the presence of biological components [68],... 

Horowitz AT, Barenholz Y, Gabizon AA. In vitro cytotoxicity of liposome-encapsulated doxorubicin dependence on liposome composition and drug release. Biochim Biophys Acta 1992 1109 203-209. 

Mayer LD, Bally MB, Cullis PR, Wilson SL, Emerman JT. Comparison of free and liposome encapsulated doxorubicin tumor drug uptake and antitumor efficacy in the SCI 15 murine mammary tumor. Cancer Lett 1990 53 183. 

Zhigaltsev IV, Maurer N, Akhong QF, et al. Liposome-encapsulated vincristine, vinblastine and vinorelbine a comparative study of drug loading and retention. J Control Release 2005 104 103. 

Liu JJ, Hong RL, Cheng WF, et al. Simple and efficient liposomal encapsulation of topotecan by ammonium sulfate gradient stability, pharmacokinetic and therapeutic evaluation. Anti-Cancer Drugs 2002 13(7) 709. 

The antimykotie amphotericine is eneapsulated in liposomes and marketed as Am-Bisome" against severe systemic mycosis. The liposomal encapsulation reduces the toxicity of amphotericine while increasing the half-life of the drug and plasma level peaks [31], For stability reasons, the parenteral formulation is a lyophilized powder whieh has to be reeonstituted by adding the solvent just before administration. 

Although ciclosporin and tacrolimus applied systemically improve psoriatic lesions, they are clearly less active when applied topically. Therefore, liposomal preparations have been developed. Indeed, ciclosporin penetrates deeper strata of rodent and human cadaver skin more efficiently when incorporated into liposomes [51], Moreover, tacrolimus concentrations in murine skin have increased ninefold, and skin graft survival prolonged, if the drug is liposome encapsulated [52]. This indicates that topical psoriasis therapy with tacrolimus may become possible. At present, topical tacrolimus is confined to the less recalcitrant forms of mild eczema. 

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