Colloids and Surfaces B: Biointerfaces 164 (2018) 177–184 Contents lists available at ScienceDirect Colloids and Surfaces B: Biointerfaces j o ur nal ho me pa ge: www.elsevier.com/locate/colsurfb Innovative topical formulations from diclofenac sodium used as surfadrug: The birth of Diclosomes Lorena Tavano ∗ , Elisabetta Mazzotta, Rita Muzzalupo Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via Pietro Bucci, Ed. Polifunzionale, 87036 Arcavacata di Rende, Italy a r t i c l e i n f o Article history: Received 6 December 2017 Received in revised form 14 January 2018 Accepted 17 January 2018 Available online 3 February 2018 Keywords: Diclofenac sodium Surfadrug Diclosomes Permeation Diclosomal gel a b s t r a c t Hypothesis: Due to the well-know surfactant-like properties of diclofenac sodium (DS), vesicular systems consisting exclusively of DS, named diclosomes, were designed with the aim to minimize or avoid the use of other excipients and to improve the formulation biocompatibility. Experiments: Diclosomes were designed and characterized in terms of dimensions, polydispersity index, -potential, drug retained, stability as a function of storage time and ex-vivo percutaneous permeation profiles. Additionally, diclosomes were incorporated into gel dosage forms and their performance in terms of permeation enhancement were evaluated. Findings: DS was found to form nanosized vesicular systems, both alone and in presence of cholesterol. Increasing hydrophobicity (due to the presence of cholesterol) resulted in smaller vesicles, always spher- ical and homogeneous in shape. Permeation of DS from free solution was found to be lower respect to ones obtained for all diclosomal formulations, allowing these aggregates to be considered as percuta- neous permeation enhancers. DS permeated from diclosomal gels was higher than that obtained with traditional niosomal gel, DS plain gel and commercial specialty Voltaren Emulgel ® 1%, while containing a considerably lower drug amount. © 2018 Elsevier B.V. All rights reserved. 1. Introduction Drug delivery systems (DDS) are a class of nanodevices able to provide enhanced efficacy and to reduce adverse side effects of therapeutics agents [1]. DDS are typically inert and they only transport drugs by forming a carrier able to encapsulate hydropho- bic or hydrophlilic drugs [2]. Moreover, they have been reported to target these compounds at desired site, with definite rate and timing. Unfortunately, despite the variety of nanocarriers devel- oped to treat diseases (i.e. nanoparticles, liposomes, polymers and proteins), success is limited to just a few formulations [3]. The most important drawback of these nanocarriers is their low drug loading capacity [4,5]. To overcome this limitation, the direct use of drug molecules as components of nanocarriers has been recently pro- posed by several researchers, with the aim to substantially increase the drug loading content, to minimize the use of inactive materials, and suppress drug premature burst release [6]. Many pharmacologically active compounds are amphiphilic molecules, which tend to self-associate and to interact with bio- ∗ Corresponding author at: Dept. Pharmacy, Health and Nutrition Sciences, Uni- versity of Calabria, 87036 Arcavacata di Rende (CS), Italy. E-mail address: uclorena@tiscali.it (L. Tavano). logical membranes likewise classical surfactants, whereby they have been defined as surfadrug (blend of surface active drug) [7]. Using an amphiphilic drug in the design of DDS would minimize or avoid the use of other excipients, improving the formulation safety and thus facilitate their clinical translation [8,9]. Thus, DDS made of sulfadrugs could represent a great innovation in the phar- maceutical field, because of their dual function: one related to the pharmacological nature of the molecule and the other related to the technological properties of the obtained carriers [10]. Addition- ally, these nanodevices may also serve as carriers of other drugs, to achieve combination therapy [10]. Classes of amphiphilic drugs including analgesics, tranquilizers, antibiotics, local anesthetics, non-steroidal antiinflammatory and chemotherapics have been extensively reviewed [8]. The structural features of amphiphilic drug molecules influence their association pattern in aqueous solution and consequently their interaction with biological membranes. Generally, sulfadrugs contain one or more flexible and hydrophobic aromatic nuclei, to which an ester group or a charge-bearing N atom is directly attached or which include a pyridine-like N atom [11]. The flexibility of the aromatic ring leads to these drugs may resemble typical surfactants in their association behaviour. In aqueous medium, surfadrugs can exist as monomers or can aggregate into micelles, bilayers and mesophases, https://doi.org/10.1016/j.colsurfb.2018.01.030 0927-7765/© 2018 Elsevier B.V. All rights reserved.