Citation: Strankowska, J.; Grzywi ´ nska, M.; Ł ˛ egowska, E.; Józefowicz, M.; Strankowski, M. Transport Mechanism of Paracetamol (Acetaminophen) in Polyurethane Nanocomposite Hydrogel Patches—Cloisite ® 30B Influence on the Drug Release and Swelling Processes. Materials 2024, 17, 40. https://doi.org/10.3390/ ma17010040 Academic Editor: Romána Zelkó Received: 27 November 2023 Revised: 18 December 2023 Accepted: 19 December 2023 Published: 21 December 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). materials Article Transport Mechanism of Paracetamol (Acetaminophen) in Polyurethane Nanocomposite Hydrogel Patches—Cloisite ® 30B Influence on the Drug Release and Swelling Processes Justyna Strankowska 1, * , Małgorzata Grzywi ´ nska 2 , Ewelina Ł ˛ egowska 3 , Marek Józefowicz 1 and Michał Strankowski 4, * 1 Institute of Experimental Physics, Faculty of Mathematics, Physics and Informatics, University of Gda ´ nsk, Wita Stwosza 57, 80-308 Gda ´ nsk, Poland; marek.jozefowicz@ug.edu.pl 2 Neuroinformatics and Artificial Intelligence Lab, Department of Neurophysiology, Neuropsychology and Neuroinformatics, Medical University of Gda ´ nsk, Tuwima 15, 80-210 Gda´ nsk, Poland 3 Academia Copernicana Interdisciplinary Doctoral School, Nicolaus Copernicus University, Lwowska 1, 87-100 Toru´ n, Poland; ewelina.legowska@gmail.com 4 Department of Polymer Technology, Chemical Faculty, Gda´ nsk University of Technology, G. Narutowicza 11/12, 80-233 Gda ´ nsk, Poland * Correspondence: justyna.strankowska@ug.edu.pl (J.S.); micstran@pg.edu.pl (M.S.); Tel.: +48-58-523-22-49 (J.S.); +48-58-347-24-34 (M.S.) Abstract: This article describes the swelling and release mechanisms of paracetamol in polyurethane nanocomposite hydrogels containing Cloisite ® 30B (organically modified montmorillonite). The transport mechanism, swelling and release processes of the active substance in nanocomposite matrix were studied using gravimetric and UV-Vis spectroscopic methods. Swelling and release processes depend on the amount of clay nanoparticles in these systems and the degree of crosslinking of PU/PEG/Cloisite ® 30B hydrogel nanocomposites. The presence of clay causes, on the one hand, a reduction in free volumes in the polymer matrices, making the swelling process less effective; on the other hand, the high swelling and self-aggregation behavior of Cloisite ® 30B and the interactions of paracetamol both with it and with the matrix, cause a change in the transport mechanism from anomalous diffusion to Fickian-like diffusion. A more insightful interpretation of the swelling and release profiles of the active substance was proposed, taking into account the “double swelling” process, barrier effect, and aggregation of clay. It was also proven that in the case of modification of polymer matrices with nanoparticles, the appropriate selection of their concentration is crucial, due to the potential possibility of controlling the swelling and release processes in drug delivery patches. Keywords: transport mechanism; diffusion; drug delivery; diffusion coefficients; swelling/release exponent; hydrogel; crosslinking; nanocomposite; paracetamol (acetaminophen); Cloisite ® 30B; clay 1. Introduction Hydrogels are three-dimensional crosslinked structures composed of polymer chains linked together in a number of crosslinks. The desired properties of hydrogels, i.e., the ability to absorb water, nontoxicity, biodegradability, porosity, flexibility, good mechanical strength, mainly depend on the type of polymers and their chemical compositions, as well as on type and amount of crosslinking agent in the matrix. Temperature, pH, mechanical forces, solvents affect the stability of hydrogels; exceeding certain critical values of these parameters leads to matrix degradation [1,2]. Due to their unique properties, hydrogels have found many applications in tissue engineering, scaffolds, biosensors, and drug carri- ers [1–6]. Hydrogel drug delivery systems have become an interesting research area due to the possibility of designing systems with desired swelling and drug release properties. Polyurethane nanocomposite hydrogels, containing sodium montmorillonite clay mineral, are a new class of hybrid materials that exhibit better mechanical properties, Materials 2024, 17, 40. https://doi.org/10.3390/ma17010040 https://www.mdpi.com/journal/materials