Liposomes topical formulations

The chemical composition of liposomes is an important parameter for their transdcrmal penetration. The most common phospholipid used for tlie preparation of topically applied liposomes is egg or soy derived phosphatidylcholine in mixtures with cholesterol. Phosholipids are very-attractive molecules for skin treatment as they combine penetration enhancement with skin hydration properties due to their tendency to bond water molecules. Their low toxicity makes them even more suitable for topical formulations. 

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. 

McCalden, T.A., and M. Levy. 1990. Retention of topical liposomal formulations on the cornea. Experientia 46 713. 

Liposomes can be easily prepared from non-toxic materials, which are non-irritant and do not obscure vision. Unfortunately, routine use of liposomes in topical ocular drug delivery is presently limited by short shelf life of the formulation, limited drag loading capacity and obstacles in sterilizing the preparation. 

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. " ... 

Fig. 2 ICAM-1 production after topical application of gamma interferon to a human skin graft on nude mice. One dose (100 pi) of a liposomal (20mg/ml lipid) or aqueous (phosphate buffered saline) formulation was applied daily for three days. Active formulation contained 0.51 mg/ml gamma interferon. Placebo liposomal formulations contained no added protein. Significant differences (active versus placebo) are indicated by asterisks ( ). (Redrawn from data in Ref. l)...

Trehalose is used for the lyoprotection of therapeutic proteins, particularly for parenteral administration. Other pharmaceutically relevant applications include use as an excipient for diagnostic assay tablets for stabilization during the freeze-thaw and lyophilization of liposomes and for stabilization of blood cells,cosmetics, and monoclonal antibodies. Trehalose may also be used in formulations for topical application. ... 

A suitable animal model can be used for in vivo pharmacokinetic assessment of a topically applied elastic liposome formulation. Rats and mice are most common but tend to provide an over-estimate compared to human skin as the skin is more permeable. Piglets provide a closer approximation to human skin permeability and have been used for some evaluations of elastic liposomes (9, 34). Appropriate animal ethics committee approval is required. A generalised protocol is outlined in the following section but there can be considerable variation depending on the complexity of information sought, i.e., if the determination of distribution into tissues is required in addition to absorption into the circulation ... 

Solubility enhancement by use of cyclodextrins is achieved for a number of drug substances, an approach of interest in formulation of drugs for topical, parenteral, and oral use (Stella and Rajewski, 1997 Loftsson and Masson, 2001 Qi and Sikorski, 2001). The solubilizing effect can be extensive even in low concentrations of cyclodextrin. The use of 0.1 M sulfobutyl-ether-P-cyclodextrin increases the solubility of prednisolone acetate and testosterone by a factor of 426 and 2020, respectively (Myrdal and Yalkowsky, 2002). Cyclodextrin encapsulation of a molecule will affect many of its physicochemical properties (Loftsson, 1995). As a result of complexation, solubility, pKa value, spectral properties, and the chemical reactivity of the included substance will change. The cyclodextrins are known to affect molecular orientation and to have an influence on rates and efficiency of electron transfer, excited state proton transfer, and rate of decomposition (Chattopadhyay, 1991 Fox, 1991 Sur et al., 2000). Cyclodextrins can also be used in combination with liposomes a cyclodextrin-liposome entity represents an even more complex environment to the drug molecule (Loukas et al., 1995). 

There are several oil-based formulations for the delivery of hydrophilic and lipophilic drugs, which maj orly include emulsions and gels (Figure 58.2). Apart from these, various other novel formulations may also be named under this category such as micelles, reverse micelles, solid lipid nanoparticles, and liposomes. - Based on the physicochemical properties of the drug and patient requirements, the vegetable oil-based formulations may be delivered by various routes like oral, parenteral, topical, transdermal, pulmonary, or ocular, etc., - ... 

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