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Niosomes are vesicles formed by the self-assembly of nonionic surfactants in aqueous dispersions. They can entrap drugs and have been used experimentally as sustained drug delivery systems. Apart from conventional spherical niosomes, various types of vesicle ultrastructures can be formed by varying the composition of the vesicle membrane. Hexadecyl diglycerol ether (C16G2), cholesterol, and poly-24-oxyethylene cholesteryl ether (Solulan C24) in the ratio 91:0:9 gave polyhedral niosomes, whereas spherical and tubular niosomes are produced at a composition ratio of 49:49:2. The mean size of both polyhedral and spherical/tubular niosomes were within the range of 6 to 9 microm. Both types of vesicle were visualized by cryo-scanning electron microscopy. The properties of the two forms of niosomes were studied using luteinizing hormone releasing hormone (LHRH) as a model peptide. Analysis by high-performance liquid chromatography demonstrated high entrapment of LHRH acetate in polyhedral niosomes when prepared by remote loading methods using pH or (NH4)2SO4 gradients; in contrast, only low entrapment was achieved by passive loading methods (direct hydration at pH 7.4 or pH 3.0, dehydration-rehydration, and reversed-phase evaporation). In vitro studies demonstrated that both polyhedral and spherical/tubular niosomes were more stable in 5% rat skeletal muscle homogenate than in rat plasma. Also, polyhedral niosomes released more radiolabeled LHRH ([125I]LHRH) than spherical/tubular niosomes in both muscle homogenate and plasma. In clearance experiments in the rat, following intramuscular injection, both polyhedral and spherical/tubular niosomes gradually released [125I]LHRH into the blood, but some radioactivity remained at the injection site for 25 and 49 h, respectively. In contrast, [125I]LHRH in phosphate buffered saline was completely cleared from the injection site at 2 h. The release of drug is sustained by both niosome formulations, but spherical/tubular niosomes possess more stable membranes than polyhedral niosomes due to the presence of cholesterol.

Rheological studies of dilute aqueous nonionic surfactant vesicle (niosome) dispersions formed mainly from hexadecyl diglycerol ether (C 16 G 2 ) or sorbitan monostearate (Span 60) were performed by capillary viscometry. By variation of the ratio of C 16 G 2 , cholesterol, and a poly-24-oxyethylene cholesteryl ether (Solulan C24), vesicles with either polyhedral or mainly spherical structures can be formed. Polyhedral niosomes transform to spherical vesicles above a transition temperature of 45 °C, while cholesterol-rich spherical/tubular niosomes remain intact up to 80 °C. These changes in niosome morphology are reflected in their rheological properties. The relative viscosity (η rel ) of spherical/tubular niosome dispersions changes little with increase in temperature, while that of polyhedral niosome dispersions decreases dramatically, indicating the transformation of the vesicles to a more spherical shape. As the intrinsic viscosity, [η], of colloidal dispersions is affected not only by vesicle shape but also by surface hydration, it is possible to make estimates of hydration. The increase in viscosity with the increase in the amount of the hydrophilic Solulan C24 in the vesicle surface is a reflection of increased hydration. However, the effect of size complicates interpretation; increase in vesicle size between 270 nm and 8.8 µm reduces the viscosity of the system. Interpretation of the intrinsic viscosity data depends to a large extent on the estimation of φ, the volume fraction occupied by the vesicles, because of internal hydration. Results are consistent with surface hydration in the range between 2 and 2.8 g g -1 for niosomes containing 10% Solulan C24 at 25 °C.

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