Liposomal products

The upscaling of liposome production methods frem the lab bench scale to an industrial level raises a number of problems. The issues which have to be addressed involve... 

Treatment fluconazole, itraconazole, ketoconazole, Amphotericin B Consider liposomal products decrease or stop CSA or TAC to minimize nephrotoxicity Remember to adjust doses of renally eliminated drugs (e.g., acyclovir, ganciclovir, TMP-SMX)... 

Additional naturally occurring lipids may be minor components of oral lipid-based formulations. Terpenes such as peppermint oil (>50% menthol) are fairly hydrophobic but can provide some solvent capacity. Steroids such as cholesterol, while important in topical and in parenteral liposomal products, are not important as oral pharmaceutical adjuvants. Phospholipids (e.g., egg or soybean phosphatidylcholine) an essential component of cell membranes, are considered polar lipids, and have surfactant properties. 

A Representative List of Liposomal Products Marketed or in Clinical Trials... 

In general, liposomes due to their physicochemical characteristics, may cause adverse effects i.e., blockage of capillaries, pulmonary embolism etc. The new technological knowledge and industrial improvements on liposomal production as well as the high quality control of the preparation procedure of the liposomal formulations can eliminate most of their undesired side effects. 

The first scale-up liposome production was performed in the cosmetic industry. The first products containing liposomes were launched in 1986 from I Oreal (Niosomes ), and Cristian Dior (Capture ), while a great number of patents appeared during the last decade (1990-2000). 

Among the several drug delivery systems, liposomes - phospholipid nanosized vesicles with a bilayered membrane structure - have drawn a lot of interest as advanced and versatile pharmaceutical carriers for both low and high molecular weight pharmaceuticals. At present, liposomal formulations span multiple areas, from clinical application of the liposomal drugs to the development of various multifunctional liposomal systems to be used in therapy and diagnostics. This chapter provides a brief overview of various liposomal products currently under development at experimental and preclinical level. 

Around 1990, the pulmonary delivery of liposomes was largely an academic exercise [43-46] and at best at an early stage of commercial development [47]. However, these and earlier efforts demonstrated the utility of liposomes, and interest has continued to flourish. This has been reinforced by greater acceptance of the dosage form, since there are now several injectable liposomal products on the market [e.g., Ambisome , Fungisome , Myocet ]. The specific use of lipid-based vehicles to deliver plasmid-based DN A has attracted much attention [48-51]. These developments have indirectly helped improve the quality and variety of... 

The merits of liposome antibiotic therapy vs. antibiotic alone seem rarely to have been compared directly. Studies have shown benefit of using some liposome antifungals [92], but the formulations were either under development or were commercialized as a liposome product for administration by injection [93]. So the debate must continue. Although liposomal formulations can be generated and aerosolized and have proved effective in combination with various drugs, do the benefits ultimately outweigh the issues developing these kinds of formulations [94] ... 

Daunorubicin (daunomycin, rubidomycin Cerubidine, others) is available for intravenous use. The recommended dosage is 30 to 60 mg/m daily for 3 days. The agent is administered with appropriate care to prevent extravasation, as severe local vesicant action may result. Total doses greater than 1000 mg/m are associated with a high risk of cardiotoxicity. A daunorubicin citrate liposomal product (Daunoxome) is indicated in the treatment of AIDS-related Kaposi s sarcoma. It is given in a dose of 40 mg/m infused over 60 minutes and repeated every 2 weeks. Patients should be advised that the drug may impart a red color to the urine. 

Therapentic uses—doxorubicin (Adriamycin, others) is available for intravenous use. The recommended dose is 50 to 75 mg/m, administered as a single rapid intravenous infusion repeated after 21 days. Care should be taken to avoid extravasation as severe local vesicant action and tissue necrosis may resnlt. A doxorubicin liposomal product (Doxil) is available for treatment of AIDS-related Kaposi s sarcoma and is given intravenously in a dose of 20 mg/m over 30 minntes and repeated every 3 weeks. 

Different techniques are used at industrial level, including spray drying and spray chilling, fluid bed coating, melt injection and melt infusion, extrusion, coacervation, crystallization, as well as emulsions and particles and liposomes production. ... 

Besides simply pouring water over the film, the vesicles can also be produced using an external stimulus like a constantly changing electrical field. This method is called electroformation and is widely used for liposome production. Upon a change in the frequency of the changing electrical field applied, the vesicles eventually detach from the surface, yielding giant polymersomes of several micrometers in diameter. 

In addition to solutions and suspensions, liposomal formulations of active substances are used and various nanoemulsion-based formulations and micellar solutions are explored for nebulisation [55]. Currently, no marketed inhaled liposomal products are available... 

Nystatin is used therapeutically in veterinary medicine as an otic product for companion animals. There is very little toxicity data either in humans or in animals available for this drug but it does appear to be maternotoxic, at least when formulated as a liposomal product, at doses of 3.0mg/kgbw/day in rats and rabbits. However, it was not teratogenic and it had no effects on reproductive parameters at doses below the maternotoxic dose. It was not ototoxic in a chinchilla model. " ... 

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