Colloids and Surfaces B: Biointerfaces 135 (2015) 400–407 Contents lists available at ScienceDirect Colloids and Surfaces B: Biointerfaces jo ur nal ho me p ag e: www.elsevier.com/locate/colsurfb Pluronic/gelatin composites for controlled release of actives Duccio Tatini, Paolo Tempesti, Francesca Ridi, Emiliano Fratini, Massimo Bonini, Piero Baglioni ∗ Dept. of Chemistry “Ugo Schiff” and CSGI, University of Florence, Via della Lastruccia 3, 50019 Italy a r t i c l e i n f o Article history: Received 23 June 2015 Received in revised form 30 July 2015 Accepted 2 August 2015 Available online 5 August 2015 Keywords: Pluronic F127 Gelatin Composite material Release kinetic Azorubine a b s t r a c t This paper describes the preparation and the release properties of composite materials based on Pluronic F127 and gelatin hydrogels, which could be of interest in the field of enteral nutrition or drug adminis- tration. The composites were prepared by exploiting the opposite responsivity to temperature of a 20% w/w Pluronic F127 aqueous solution (critical gelation temperature around 23 ◦ C) and gelatin (gel–sol temperature transition around 30 ◦ C). Pluronic domains dispersed within a gelatin matrix were obtained by injecting cold Pluronic F127 solutions inside hot gelatin solutions, while homogenizing either with a magnetic stirrer or a high-energy mechanical disperser. Calorimetry indicates that the composites retain the individual gelling properties of Pluronic and gelatin. Different releasing properties were obtained as a function of the preparation protocol, the temperature and the pH. The release profiles have been studied by a Weibull analysis that clearly points out the dominating role of gelatin at 25 ◦ C. At 37 ◦ C the release accounts for a combined effect from both Pluronic F127 and gelatin, showing a more sustained profile with respect to gelatin hydrogels. This behavior, together with the ability of Pluronic F127 to upload both hydrophilic and hydrophobic drugs and flavors, makes these innovative composite materials very good candidates as FDA-approved carriers for enteral administration. © 2015 Elsevier B.V. All rights reserved. 1. Introduction Hydrogels are three-dimensional polymeric networks capable of uploading high amounts of water or biological fluids [1], com- monly used in a wide range of applications such as cosmetic, pharmaceutical, biomedical and food industry [2]. In the past few years, hydrogels have been extensively stud- ied in the development of smart drug delivery systems [3]. As a matter of fact, these systems offer several advantages that poten- tially improve the pharmacological and therapeutic properties of the administered drugs. For instance, hydrogels can protect the active agents from hostile environments (e.g., the low pH in stom- ach or the presence of enzymes), as well as to control the release in response to environmental stimuli. In the view of their applications in enteral nutrition or drug administration (i.e., oral, sublingual and rectal administration of drugs and/or nutrients), hydrogels based on naturally-occurring polymers show optimal biocompatibility and allow for multiple strategies for drug delivery [4]. To this aim, gelatin is a very promis- ing candidate, as it is a natural polymer obtained by the partial ∗ Corresponding author. Phone: +39 055 457 3033. E-mail address: baglioni@csgi.unifi.it (P. Baglioni). hydrolysis of collagen extracted from skin, bones, and connective tissues of animals [5,6]. Furthermore, composite materials made of gelatin hydrogels in combination with ceramics, natural and syn- thetic polymers have been developed for the controlled delivery of therapeutics and bioactive agents [7]. Composite systems combine two or more materials to generate a novel system with unique fea- tures, such as enhanced mechanical properties [8], responsivity to external stimuli [9,10], or controlled release [11,12]. In particular, it has been demonstrated that the release mechanism of therapeutic agents from gelatin-based composites can be tuned both via tem- perature [13] and pH [14]. However, their usage has been severely limited by high dissolution rate of the gelatin-based composites in physiological conditions [7], which has led to various cross-linking strategies to obtain a stable and biocompatible material. Unfor- tunately, cross-linking agents such as glutaraldehyde have been proven to be cytotoxic to different extents [15]. This has encour- aged the research of new cross-linkers displaying reduced toxicity [16,17] and new approaches to improve their reactivity [18]. Pluronic F127 solutions are known to have a peculiar behav- ior with temperature: in particular above its critical micellization temperature (CMT) this polymer self-assembles into micelles and a further temperature increase leads to the interaction among micelles, eventually forming a hydrogel [19]. The process is fully reversible and the sol–gel transition temperature, indicated as criti- http://dx.doi.org/10.1016/j.colsurfb.2015.08.002 0927-7765/© 2015 Elsevier B.V. All rights reserved.