Citation: Altunta¸ s, E.; Özkan, B.; Güngör, S.; Özsoy, Y. Biopolymer-Based Nanogel Approach in Drug Delivery: Basic Concept and Current Developments. Pharmaceutics 2023, 15, 1644. https://doi.org/10.3390/ pharmaceutics15061644 Academic Editors: Susana C. M. Fernandes and Garbine Aguirre Received: 27 April 2023 Revised: 29 May 2023 Accepted: 30 May 2023 Published: 2 June 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/). pharmaceutics Review Biopolymer-Based Nanogel Approach in Drug Delivery: Basic Concept and Current Developments Ebru Altunta¸ s 1 , Burcu Özkan 2 , Sevgi Güngör 1 and Yıldız Özsoy 1, * 1 Faculty of Pharmacy, Department of Pharmaceutical Technology, Istanbul University, 34116 Istanbul, Türkiye; ebru.altuntas@istanbul.edu.tr (E.A.); sgungor@istanbul.edu.tr (S.G.) 2 Graduate School of Natural and Applied Science, Yildiz Technical University, 34220 Istanbul, Türkiye; burcu_ozkan93@hotmail.com * Correspondence: yozsoy@istanbul.edu.tr; Tel.: +90-533-7630969 Abstract: Due to their increased surface area, extent of swelling and active substance-loading capacity and flexibility, nanogels made from natural and synthetic polymers have gained significant interest in scientific and industrial areas. In particular, the customized design and implementation of nontoxic, biocompatible, and biodegradable micro/nano carriers makes their usage very feasible for a range of biomedical applications, including drug delivery, tissue engineering, and bioimaging. The design and application methodologies of nanogels are outlined in this review. Additionally, the most recent advancements in nanogel biomedical applications are discussed, with particular emphasis on applications for the delivery of drugs and biomolecules. Keywords: biopolymers; nanogels; drug delivery; polysaccharide-based nanogels; protein-based nanogels; nanotechnology 1. Biopolymer-Based Microgels/Nanogels as a Drug Delivery System Researchers are constantly exploring new materials with enhanced properties that can be employed in a number of biomedical applications, including as drug delivery systems, prosthetic devices, theranostics, drug targeting, magnetic resonance imaging, and tissue engineering scaffolds [1]. Through the creation of materials at the nanoscale level, the development of nanotechnology altered various medical processes and technologies. Due to their improved characteristics over their bulk counterparts, nanoscale materials are important in the field of drug delivery. Recent research demonstrated the significance of the nanoscale size range in a variety of drug delivery methods, including hydrogels, which sparked the creation of micro- (microgels) and nanoscale hydrogels (nanogels) [2,3]. Microgels, also referred to as nanogels, are hydrogel particles sized in the submicron range [4,5]. The 3D cross-linked hydrogel nanoparticles known as nanogels have grown in attraction as nanoparticulate drug delivery systems [6]. Three-dimensional hydrogel particles with submicron particle sizes are used in nanogel delivery systems. Nanogels are produced in aqueous solutions by combining hydrophilic, hydrophobic, or amphiphilic polymers chemically or physically (noncovalent attractive forces such as hydrophilic– hydrophilic, hydrophobic–hydrophobic, ionic contacts, and/or hydrogen bonding) [7–10]. Nanogels have the ability to absorb liquid while maintaining their structural integrity thanks to polymer internal crosslinking [11]. Nanogels can be produced using polymers that are synthetic, natural, or a combination of both and depending on the methods of synthesis applied, nanogels can be formed into various shapes such as core–shell structures, spherical particles, or core–shell–corona structures [12]. Proteins and polysaccharides that are chosen for their biodegradability and low immunogenicity may also be included in nanogel-forming components. These are designed to be very effective at enhancing the drug payload in the targeted area and reducing the tendency that the loaded bioactives will leak from all other nanocarriers [10]. Pharmaceutics 2023, 15, 1644. https://doi.org/10.3390/pharmaceutics15061644 https://www.mdpi.com/journal/pharmaceutics