Amphotericin liposomal encapsulation

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). 

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. 

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. 

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. 

Liposomal encapsulation or incorporation in a lipid complex can substantially affect a drug s functional properties relative to those of the unencapsulated or nonlipid-associated drug. Lipid-based formulations increase the circulation time and alter the biodistribution of associated amphotericin. Increasing drug levels at site of action and reducing levels in normal tissues offers 2 distinct clinical advantages An increased therapeutic index and altered toxicity profile relative to free drug. 

Liposomal encapsulation has the potential not only to increase the activity and prolong the residence of the drag in the eye, but also to reduce the intraocular toxicity of certain potent drags such as antimetabolites, antivirals and antibiotics to the retina. For example, liposome-encapsulated amphotericin B produced less toxicity than the commercial amphotericin B solution when injected intravitreally. Liposomes have also been used to study the release and distribution of dyes, which in turn reflect the integrity of the retinal vascular constitution. Direct intravitreal injection of liposomal-encapsulated drags has shown enhanced vitreal levels for extended periods of time in the vitreous of rabbit models. Liposomal encapsulation of the antiviral, HPMPC, reduces the toxic effects to the retina and provides therapeutic levels against CMV retinitis for up to 8 months. 

Amphotericin B encapsulated in charged liposomes demonstrated 10-fold higher transport rates across the skin compared with neutral liposomes [279], In a similar manner, the retention of acyclovir from positively charged vesicles was much higher compared with other formulations [277], This could be attributed to the attraction... 

Anaissie E, Paetznick V, Proffitt R, et ai. Comparison ofthe in vitro antifungal activity of free and liposome-encapsulated amphotericin B. Eur J Clin Microbiol Infect Dis 1991 10 665-8. 

Gondal JA, Swartz RP, Rahman A. Therapeutic evaluation of free and liposome-encapsulated amphotericin B in the treatment of systemic candidiasis in mice. Antimicrob Agents Chemother 1989 33 1544-8. 

Lopez-Berestein G, Mehta R, Hopfer RL, et ai. Treatment and prophylaxis of disseminated infection due to Candida albicans in mice with liposome-encapsulated amphotericin B. J Infect Dis 1983 147 939-45. 

Meunier F, Sculier JP, Coune A, Brassinne C, Heyman C, Laduron C, Collette N, Hollaert C, Bron D, Klastersky J. Amphotericin B encapsulated in liposomes administered to cancer patients. Ann NY Acad Sci 1988 544 598-610. 

Ringden 0, Meunier F, Tollemar J, Ricci P, Tura S, Kuse E. Efficacy of amphotericin B encapsulated in liposomes (AmBisome) in the treatment of invasive fungal infections in immunocompromised patients. J Antimicrob Chemother 1991 28 73-82. 

Pontacii, Sun D, Brown JW, Shahied SI, PIcscia OJ, Schaffner CP. Lopez-Berestein G, Sarin PS. Inhibition of HIV replication by liposomal encapsulated amphotericin B. Antivi lal Res 1989 11 119-125. 

Several newer forms of amphotericin B (Abelcet, AmBisome, Amphotec) have also been developed. These drugs are encapsulated in small lipid spheres (liposomes) and then injected slowly by intravenous infusion.26,57 The lipid-based preparations appear to deliver higher doses of amphotericin B to the site of... 

DaunoXome , used in treatment of Kaposi s sarcoma, is an example of a liposomal antineoplastic medicine. Daunorubicin hydrochloride (1 mg/mL) is encapsulated in small liposomes. Amphotericin B, which is used in the treatment of systemic fungal infection, is also formulated as a stable colloidal particle. 

Supercritical fluids/gas/anti- solvent method PEG/PLA, PLGA, PVP, Poly(3-hydro- xybutyrate-co-3- hydroxjrvalerate) (PHBV), Ethylcellulose/ methylcellulose. Phospholipids, Liposomes, Itraconazole, Paclitaxel, Amphotericin B, Oxeglitazar, Beclomethasone, Naproxen, Low molecular weight heparins (LMWH) High encapsulation efficiencies, uniform particle size, easy to scale up, no toxicity due to complete solvent removal High cost of equipment, difficulty in finding proper emulsion solvents [97-99]... 

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