Preparation and In Vitro Evaluation of Miconazole Nitrate–Loaded Topical Liposomes

nitrate is a widely used antifungal agent, but its use in topical formulations is not efficacious because deepseated fungal infections are difficult to treat with conventional topical formulations. The entrapment of a drug in liposomes can facilitate localized delivery of the drug, and improved availability by means of a controlled-release pattern can advance the treatment of deep fungal infections. This study examined critical parameters such as lipid composition, type of lipid, and charge, and the prepared products were characterized for liposome-specific properties such as microscopic appearance, size, and degree of drug entrapment. Significant retention of miconazole in skin was observed with the use of liposomes. iconazole nitrate (MCZ) is a broad-spectrum antifungal agent of the imidazole group (1). It acts by means of a combination of two mechanisms: ergosterol biosynthesis inhibition, which causes lysis of fungal cell membranes because of the changes in both membrane integrity and fluidity, and direct membrane damage of the fungal cells. The drug is primarily used as a topical treatment for cutaneous mycoses (2); poor dissolution and lack of absorption make it a poor candidate for oral administration. However, MCZ can be used as a systemic antifungal agent when amphotericin B or ketoconazole is either ineffective or contraindicated. MCZ’s poor skin-penetration capability presents a problem in the treatment of cutaneous diseases by topical application. For effective treatment, the drug must be delivered in sufficient concentration to the site of infection (3). Various approaches have been used to enhance the access of such poorly skin-partitioned drug molecules. For example, the use of complexation with cyclodextrins has been reported to improve oral and topical delivery of MCZ (4,5). Other approaches have used submicron emulsions of MCZ for improved topical delivery (6,7) and chewing gum containing MCZ for buccal delivery (8,9). Several reports have described the potential use of liposomes to topically deliver drugs into the deep layers of the skin. The authors examined the use of closed lamellar vesicles whose unique structural and functional features facilitate the delivery of dermal drugs because they are biodegradable, nontoxic, amphiphilic in nature, penetration enhancing, and effective for modulating drug-release properties. These smectic mesophasic structures can be modified in terms of their size, shape, lamellae nature, and the type of composition used. The successful launch of the antifungal agent econazole (Pevaryl, CILAG, AG, Switzerland) on the market encouraged further exploration and exploitation of these molecules to make them more effective (10). Various studies have assessed the individual characteristics of MCZ, including degree of entrapment, size profile, drugrelease profile, and ability to carry the drug across the skin barrier. The analysis of MCZ in liposomes was determined using second-order derivative spectrophotometry (a simple spectrophotometric technique is not sensitive enough to produce accurate results for estimating a low amount of drug) (11,12).