Design and characterization of fenretinide containing organogels Elisabetta Esposito, Enea Menegatti, Rita Cortesi ⁎ Department of Life Sciences and Biotechnology, University of Ferrara, I-44121 Ferrara, Italy abstract article info Article history: Received 19 March 2012 Received in revised form 10 July 2012 Accepted 1 September 2012 Available online 8 September 2012 Keywords: Fenretinide Lecithin Organogel Microemulsion Hyaluronic acid The stable, transparent, organogels, which are prepared by adding a minute amount of water to a solution of lecithin in biocompatible oil, are here studied as matrices for solubilization and percutaneous delivery of fenretinide (4 hydroxypropyl phenyl retinamide, 4HPR), a retinoic acid derivative. The influence of different types of oil, content of water and presence of hyaluronic acid was studied on gel properties. Rheology studies were carried out in order to detect the effect of these variables on gel viscosity. 4HPR diffusion from the dif- ferent organogels was determined by in vitro Franz cell. It was found that diffusion coefficients (J n ) of 4HPR incorporated in organogels are about five fold lower than J n of 4HPR in organic solution. Stability and shelf life stability studies demonstrate that 4HPR incorporated in organogels does not degrade and that organogels maintain 90% of 4HPR stability for periods up to 4 months. © 2012 Elsevier B.V. All rights reserved. 1. Introduction Fenretinide (4 hydroxypropyl phenyl retinamide, 4HPR) is a syn- thetic amide derivative of all-trans- retinoic acid, one of the less toxic vitamin A analogues [1,2]. 4HPR has been applied in the chemoprevention and in the treat- ment of different types of malignancies including breast cancer, neu- roblastoma, prostate, and pancreas cancers. Moreover 4HPR is proposed for the treatment of many topical tumours such as oral li- chen planus and leukoplakias, skin tumours (e.g. basal cell carcinoma, BCC, and squamous cell carcinoma, SCC) and some other skin diseases (e.g. actinic keratosis) [3–6]. The most frequently reported side effects of 4HPR involve visual and ophthalmologic problems; however, its relatively low pharmaco- logical toxicity as compared with other retinoids [7] has made it an attractive candidate for a number of trials in which it has been stud- ied alone or in conjunction with other chemotherapeutic agents [3,8]. Despite its pharmacologic advantages, 4HPR is difficult to admin- ister because of its low solubility in aqueous medium (log P = 7.41). In a study by Moglia and colleagues the authors report on the efficacy of 4HPR on actinic keratosis treated topically with the formulation usually taken orally [9]. In this respect the need of an appropriate vehicle for topical 4HPR administration appears mandatory [10]. BCC and SCC are the most common form of skin cancers. BCC usu- ally presents as a raised, smooth, pearly bump on the sun-exposed skin of the head, neck or shoulders [11]. In the same zones SCC ex- hibits a growing bump that may have a rough, scaly surface and flat reddish patches [12,13]. Surgery is the most frequent approach used to treat BCC and SCC, often leading to scarring [14,15]. Some authors have proposed a non-surgical treatment of SCC based on an intralesionally injection of a gel [15], at this regard a less invasive al- ternative can be represented by the use of a transdermal formulation. A semisolid formulation constituted of biocompatible materials able to assure targeted delivery of actives, minimizing at the same time toxic systemic effects appears the ideal solution to treat cutane- ous pathologies. An innovative non-aqueous semisolid system is rep- resented by the lecithin organogel [16]. Lecithin is a non-toxic, naturally occurring biocompatible surfac- tant; it can be considered as one of the most promising and useful agents able to increase the skin permeation. Lecithin is able to form poly molecular structures such as gel-like reverse micellar systems [17,18]. The lecithin organogel consists of reversed polymer-like micelles [19]. They are generated from the initial spherical ones by dissolving trace amounts of water in a non-aqueous solution of lecithin [20]. The micellar aggregates entangle, forming a temporal three-dimensional network in the bulk phase [21]. These gel-like reverse micellar systems are particularly interesting due to their ability to solubilize substances with different chemico-physical properties, their thermodynamic sta- bility and their biocompatibility [22]. Many studies demonstrated that a wide variety of guest molecules such as vitamins A and C, hormones, NSAIDS, peptides, amino acids, enzymes of pharmaceutical importance (i.e. lipase, proteases, and L-asparaginase), local anaesthetics and anti- fungal agents can be efficiently carried by lecithin organogels. In addi- tion lecithin organogels have also been found to be excellent matrixes for the delivery of macromolecules with a molecular weight of 33000 Da [20,21]; thus, proteins can also be incorporated within leci- thin organogels. The penetration enhancer property of lecithin gives Materials Science and Engineering C 33 (2013) 383–389 ⁎ Corresponding author at: Department of Life Sciences and Biotechnology, Via Fossato di Mortara, 19, I-44121 Ferrara, Italy. Tel.: +39 0532 455259; fax: +39 0532 455953. E-mail address: crt@unife.it (R. Cortesi). 0928-4931/$ – see front matter © 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.msec.2012.09.002 Contents lists available at SciVerse ScienceDirect Materials Science and Engineering C journal homepage: www.elsevier.com/locate/msec