Citation: Hanmantrao, M.; Chaterjee, S.; Kumar, R.; Vishwas, S.; Harish, V.; Porwal, O.; Alrouji, M.; Alomeir, O.; Alhajlah, S.; Gulati, M.; et al. Development of Guar Gum-Pectin-Based Colon Targeted Solid Self-Nanoemulsifying Drug Delivery System of Xanthohumol. Pharmaceutics 2022, 14, 2384. https://doi.org/10.3390/ pharmaceutics14112384 Academic Editors: Avi Domb and Leonard I. Wiebe Received: 16 September 2022 Accepted: 2 November 2022 Published: 5 November 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/). pharmaceutics Article Development of Guar Gum-Pectin-Based Colon Targeted Solid Self-Nanoemulsifying Drug Delivery System of Xanthohumol Mahesh Hanmantrao 1 , Sourabh Chaterjee 1 , Rajan Kumar 1 , Sukriti Vishwas 1 , Vancha Harish 1 , Omji Porwal 2 , Mohammed Alrouji 3 , Othman Alomeir 4 , Sharif Alhajlah 3 , Monica Gulati 1,5 , Gaurav Gupta 6,7,8 , Kamal Dua 5,9 and Sachin Kumar Singh 1,5, * 1 School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, India 2 Department of Pharmacognosy, Faculty of Pharmacy, Tishk International University, Erbil 4401, Iraq 3 Department of Medical Laboratories, College of Applied Medical Sciences, Shaqra University, Shaqra 11961, Saudi Arabia 4 Department of Pharmacy Practice, College of Pharmacy, Shaqra University, Shaqra 11961, Saudi Arabia 5 Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia 6 School of Pharmacy, Suresh Gyan Vihar University, Mahal Road, Jagatpura, Jaipur 302017, India 7 Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai 602105, India 8 Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun 248007, India 9 Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, NSW 2007, Australia * Correspondence: singhsachin23@gmail.com or sachin.16030@lpu.co.in; Tel.: +91-9888720835 Abstract: Present study deciphers development of oral polysaccharide-based colon targeted solid self-nanoemulsifying drug delivery system (S-SNEDDS) of xanthohumol (XH). Several studies have shown that XH has anti-inflammatory and antioxidant properties, suggesting that it could be a good candidate for the treatment of colorectal diseases (CRD). Despite its potential, XH has a low aqueous solubility. As a result, its bioavailability is constrained by the dissolution rate. The liquid (L)-SNEDDS was constituted using Labrafac PG as oil, Tween 80 as surfactant and Transcutol P as co-surfactant. The L-SNEDDS was then adsorbed onto the surface of guar gum and pectin and developed into S-SNEDDS powder. Ternary phase diagram was used to optimize the process of developing L-SNEDDS. The formulation showed mean droplet size of 118.96 ± 5.94 nm and zeta potential of −19.08 ± 0.95 mV and drug loading of 94.20 ± 4.71%. Dissolution studies carried out in medium containing rat caecal contents (RCC) represented the targeted release of S-SNEDDS powder. It was observed that S-SNEDDS showed less than 10% release XH in initial 5 h and rapid release occurred between the 5th and 10th hour. Results of cytotoxicity studies revealed good cytotoxicity of XH loaded S-SNEDDS for Caco2 cells as compared to raw-XH. Keywords: xanthohumol; solid self-nanoemulsifying drug delivery system; guar gum; colon targeted delivery system; quality by design 1. Introduction Xanthohumol (XH) is a prenylated flavonoid extracted from the female flowers of the hops plant (Humulus lupulus L.), which is primarily found in Germany and China [1]. XH is chemically known as 30-[3,3-dimethyl allyl]-20,40,4-trihydroxy-60-methoxychalcone [2]. The main constituent of the hop plant, which belongs to the Humulus genus and is a member of the Cannabaceae family, is XH. Because of its aroma and bitter taste, it is one of the ingredients used in beer [3]. This herbal drug shows promising anti-inflammatory [4], antioxidant [5], and anti-cancer [6] properties that can be used in the treatment of CRD. The oral route is the most preferred route for the administration of drugs due to its advantages such as ease of administration, controllable dosage regimen, flexibility Pharmaceutics 2022, 14, 2384. https://doi.org/10.3390/pharmaceutics14112384 https://www.mdpi.com/journal/pharmaceutics