Invasomes: Vesicles for Enhanced Skin Delivery of Drugs

Abstract

This chapter describes invasomes, which represent novel vesicular carriers for enhanced skin delivery. Invasomes are composed of unsaturated phospholipids, small amounts of ethanol and terpenes, and water. Different penetration studies performed in vitro in human skin will be represented in order to show the penetration-enhancing ability of invasomes. The first used invasomes or standard invasomes contained a terpene mixture, composed of cineole:citral:d-limonene = 45:45:10 v/v and were shown to be more efficient in delivering highly lipophilic and hydrophobic drugs into the skin, such as cyclosporine A (CsA) and temoporfin (mTHPC), compared to conventional liposomes and the ethanolic solution of drugs. It was also shown that invasomes significantly increased the permeation of hydrophilic drugs, like calcein and carboxyfluorescein, compared to conventional and deformable liposomes. Furthermore, also other terpene mixtures and single terpenes can be used to formulate invasomes, and dependent on the added terpene or terpene mixture, invasomes may enhance or retard the drug penetration into the skin compared to liposomes without terpenes. The presence of 1 % w/v citral, 1 % w/v cineole, or 1 % w/v standard terpene mixture in invasomes resulted in the formation of highly effective skin delivery systems for mTHPC, especially in the case of invasomes with 1 % w/v cineole providing high amounts of mTHPC not only in the SC but also in the deeper skin layers. As to the therapeutic effectiveness, the effectiveness of CsA invasomes containing 2 % w/v standard terpene mixture was confirmed in the treatment of alopecia areata in the Dundee Experimental Bald Rat (DEBR), while mTHPC invasomes containing 1 % w/v standard terpene mixture provided a slower tumor growth in mice bearing the subcutaneously located human colorectal HT29 carcinoma. The key factor for the high penetration-enhancing ability of invasomes is assumed to be their high fluidity confirmed by electron spin resonance, differential scanning calorimetry, and cryoelectron microscopy. However, as no direct correlation between the fluidity of invasomes and their ability to improve skin penetration of drugs was found, it is proposed that besides the fluidity, also other phenomena might be involved in the mechanism of the skin penetration enhancement induced by invasomes.