Cyclosporin liposomal delivery

S. M. Dowton, Z., Hu, C. Ramachandran, D. F. H. Wallach, and N. Weiner, Influence of liposomal composition on topical delivery of encapsulated cyclosporin A, I. An in vitro study using hairless mouse skin, STP Pharma Sciences 3 404-407 (1993). 

Liposomes to deliver cyclosporin A (CsA) have been incorporated into collagen shields. This delivery system provided the highest levels of CsA in both the cornea and sclera with higher levels in the aqueous humor compared to unencapsulated and capsulated CsA but not loaded into collagen shields. 

Unfortunately, the number of commercial formulations is very limited, primarily because of stability and manufacturing problems encountered during large-scale production. The list includes Sandimmune Neoral (cyclosporine A Novartis AG, Switzerland), which contains a microemulsion preconcentrate and is available as soft gels and solutions. Sandimmune (cyclosporine A Novartis AG, Switzerland), which contains an emulsion preconcentrate, and lipid soluble vitamins. Both formulations of cyclosporine have self-emulsifying properties and spontaneously form an o/w microemulsion (particle size <0.15 pm) and an o/w emulsion, respectively in the aqueous fluids of the GI tract. Although the discussion concerning potential of liposomes, niosomes, microemulsions, and solid dispersions for oral delivery is outside the scope of this chapter, the interested reader is referred to recently published reviews on these topics. " ... 

Nephrotoxicity is best minimized by limiting the cumulative dose and avoiding concomitant administration of other nephrotoxins, particularly cyclosporine. Additionally, providing hydration with a high sodium diet and 1 L intravenous 0.9% sodium chloride daily appears to reduce toxicity. Mannitol infusion to induce an osmotic diuresis has not been protective. Lastly, several liposomal amphotericin B formulations are now available and have been reported to reduce nephrotoxicity by enhancing drug delivery to sites of infection and thereby reducing exposure of mammalian cell membranes. ... 

Ophthalmic delivery For administration of water-insoluble drugs into the eye, colloidal systems are used. Surface active polymers, such as polyvinyl alcohol, poloxamer, and methylcellulose are often added as particle stabilizers and viscosity enhancers. Particle size in such colloidal systems should not exceed 5-10 pm in diameter. Emulsions, liposomes, and micro- and nanoparticles, all stabilized by surfactants, are used in topical ophthalmic drug delivery [56]. For instance, an ophthalmic preparation of cyclosporin A, Restasis , is an emulsion stabilized by polysorbate 80 and polymer carbomer 1342. 

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