Citation: Ajaz, N.; Khan, I.U.; Irfan, M.; Khalid, S.H.; Asghar, S.; Mehmood, Y.; Asif, M.; Usra; Hussain, G.; Shahzad, Y.; et al. In Vitro and Biological Characterization of Dexamethasone Sodium Phosphate Laden pH-Sensitive and Mucoadhesive Hydroxy Propyl β-Cyclodextrin-g-poly(Acrylic Acid)/Gelatin Semi-Interpenetrating Networks. Gels 2022, 8, 290. https:// doi.org/10.3390/gels8050290 Academic Editor: Jinfeng Liao Received: 9 April 2022 Accepted: 29 April 2022 Published: 7 May 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 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/). gels Article In Vitro and Biological Characterization of Dexamethasone Sodium Phosphate Laden pH-Sensitive and Mucoadhesive Hydroxy Propyl β-Cyclodextrin-g-poly(Acrylic Acid)/Gelatin Semi-Interpenetrating Networks Nyla Ajaz 1 , Ikram Ullah Khan 1 , Muhammad Irfan 1 , Syed Haroon Khalid 1 , Sajid Asghar 1 , Yasir Mehmood 1 , Muhammad Asif 2 , Usra 3 , Ghulam Hussain 3 , Yasser Shahzad 4 , Shefaat Ullah Shah 5 and Muhammad Usman Munir 6, * 1 Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad 38000, Pakistan; nylaajaz@gmail.com (N.A.); ikramglt@gmail.com (I.U.K.); manipharma1@gmail.com (M.I.); haroonkhalid80@gmail.com (S.H.K.); sajuhappa@gmail.com (S.A.); yasirmehmoodamjad@gmail.com (Y.M.) 2 Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan; drmasif@iub.edu.pk 3 Department of Physiology, Government College University Faisalabad, Faisalabad 38000, Pakistan; usrakhan1990@gmail.com (U.); hussain806@gmail.com (G.H.) 4 Department of Pharmacy, COMSATS University Islamabad, Lahore Campus, Lahore 54700, Pakistan; yasi.shahzad@gmail.com 5 Skin/Regenerative Medicine and Drug Delivery Research, GCPS, Faculty of Pharmacy, Gomal University, Dera Ismail Khan 29050, Pakistan; shefaatbu@gmail.com 6 Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka 72388, Saudi Arabia * Correspondence: mumunir@ju.edu.sa Abstract: The current study reports the fabrication and biological evaluation of hydroxy propyl β-cyclodextrin-g-poly(acrylic acid)/gelatin (HP-β-CD-g-poly(AA)/gelatin) semi-interpenetrating networks (semi-IPN) for colonic delivery of dexamethasone sodium phosphate (DSP). The prepared hydrogels showed pH-dependent swelling and mucoadhesive properties. The mucoadhesive strength of hydrogels increased with an increasing concentration of gelatin. Based on the swelling and mucoadhesive properties, AG-1 was chosen as the optimized formulation (0.33% w/w of gelatin and 16.66% w/w of AA) for further analysis. FTIR revealed the successful development of a polymeric network without any interaction with DSP. SEM images revealed a slightly rough surface after drug loading. Drug distribution at the molecular level was confirmed by XRD. In vitro drug release assay showed pH-dependent release, i.e., a minute amount of DSP was released at a pH of 1.2 while 90.58% was released over 72 h at pH 7.4. The optimized formulation did not show any toxic effects on a rabbit’s vital organs and was also hemocompatible, thus confirming the biocompatible nature of the hydrogel. Conclusively, the prepared semi-IPN hydrogel possessed the necessary features, which can be exploited for the colonic delivery of DSP. Keywords: semi-interpenetrating network; hydroxy propyl β cyclodextrin; gelatin; acrylic acid; dex- amethasone 1. Introduction Polymeric drug delivery systems are playing an important role in the safe and effective delivery of active pharmaceutical agents. Multicomponent polymeric delivery systems give opportunities to tailor the properties of carriers by manipulating the proportion of individual components. For instance, hydrogels are three-dimensional polymeric networks, which have the ability to retain a large portion of water. These homo or copolymer networks are often weak and gave a premature release of encapsulated drugs. Such Gels 2022, 8, 290. https://doi.org/10.3390/gels8050290 https://www.mdpi.com/journal/gels