Development of innovative formulations for topical administration of vitamin K1

Abstract

The research activity has been focused on the study of new strategies for the dermal and transdermal administration of pharmacologically active molecules. In particular, the study was aimed to develop formulations based on nanocarriers for the administration of vitamin K1 (phylloquinone) in aerosol form on the skin. Recently, it was found that creams containing vitamin K1 was very useful in the prevention of acneiform reactions affecting the skin in patients receiving cetuximab for the treatment of metastatic colorectal cancer. (Ocvirk Janja et al., 2010, Tomkova et al., 2011). Different semisolid formulations containing vitamin K1, namely Rencoval®, VigorSkinK1® and VigorSkinK1 Plus®, are already present on the market. The purpose of this study was therefore to develop alternative strategies for the administration of vitamin K1 on the skin, overcoming the drawbacks associated with the use, for more administration in a day, of fatty formulations. Therefore, innovative aqueous formulations to be administered on the skin by aerosol, thus avoiding the use of semisolid preparations, have been designed and developed in this work. To nebulize the developed formulations, a patented device (Eaute), portable and pocket with battery was used. In the development of vitamin K1-containing formulation alternative to the lipophilic formulations currently on the market, the possibility to increase the accumulation of vitamin in the epidermis and dermis was also taken into account. The formulative strategies used in this work start from previous published findings on lipid-based nanocarriers, such as liposomes, already used to administer different drugs on the skin. Then, the possibility to develop transfersomes and ethosomes to increase, compared to liposome-based formulations, the vitamin accumulation into the skin was investigated. Finally, the possibility to use lipid-free nanoemulsions, to propose formulative approaches less expensive for future commercial development, has been investigated. Thus, during all the experimental work, special attention was paid on the development of formulations suitable to be transferred to the industry (technological transfer). Thus, once designed the different formulations, their optimization has been aimed to combine high encapsulation of active compound, absent o low release of the encapsulated molecule during storage, long shelf-life, as well as increased accumulation into the skin. This PhD work has been carried out in collaboration with the Xenus s.r.l. in the respect of a confidential agreement between the PhD student, the University Tutor prof. Giuseppe De Rosa and the scientific responsible of the company dr. Michele Pitaro, some experimental details of this work have been omitted in this thesis.