273-279| Special Issue | 2022 ISSN: 0974-1496 | e-ISSN: 0976-0083 | CODEN: RJCABP http://www.rasayanjournal.com http://www.rasayanjournal.co.in Rasayan J. Chem., Special Issue, 273-279(2022) http://doi.org/10.31788/RJC.2022.1558166 This work is licensed under a CC BY 4.0 license. SYNTHESIS AND CHARACTERIZATION OF HYDROXY PROPYL METHYL CELLULOSE-BASED CITRIC ACID CROSSLINKED NANOGELS OBTAINED VIA GREEN PROTOCOL Rohini Dharela 1, , Anupama Kaushik 2 and Ghanshyam S. Chauhan 3 1 Department of Chemistry, Alakh Prakash Goyal Shimla University, Shimla-171013, Himachal Pradesh, India 2 S. S. Bhatnagar University Institute of Chemical Science and Engineering, Chandigarh-160014, India 3 Department of Chemistry, Himachal Pradesh University, Summerhill, Shimla-171005, Himachal Pradesh, India  Corresponding Author: rohinidharela@gmail.com ABSTRACT Nanogels are versatile tools in the hands of a biochemist, increasingly being used for medicinal applications and as bio-sensing tools. The utilization of biopolymer-based nano gels is a field that still has much exploration to be done. In this article, we will study the Hydroxypropyl Methyl Cellulose (HPMC)-based Citric Acid (CA) cross-linked nanogels synthesized via a green protocol. The nanogels were synthesized following a novel technique without using a surfactant at 55°C by employing citric acid as a crosslinker and Acryl Amide (AAm) as a co-polymer. The nanogels synthesized were categorized with swelling studies, FTIR, Particle size Analyzers and FESEM that provided proof for co-polymer synthesis and nanogel formation. The particle size analysis of HPMC- co- poly(AAm)-cl-CA nanogels indicated a particle size below 10nm with spherical nature that was supported by FESEM data that presented spherical particles with a size below 50nm. The swelling studies carried out at acidic (4.0) and basic pH (7.0) exhibited their pH sensitivity as the nanogels showed 40% higher swelling at 7.0 pH than 4.0 indicating these could be utilized for site-specific drug delivery. Keywords: Biopolymer, Nanogels, Swelling, Polymers, Hydrogels. RASĀYAN J. Chem., Special Issue, 2022 The manuscript is focusing SDG-12: Responsible Consumption and Production INTRODUCTION Nanogels are nano-sized hydrogels with a size range of 10-200nm, having properties of both hydrogels and nanoparticles. Initially, the term ‘nanogel’ was used for a bifunctional system of polyionic and cross- linked polyethyleneimine (PEI) or non-ionic polymer and Poly Ethylene Glycol (PEG-cl-PEI) for antisense oligonucleotides delivery. 1,2 They have three-dimensional network nanostructures with a higher specific surface area than hydrogels. Due to their small size, nanogels respond rapidly to changes in the environment like temperature or pH changes. They are formed by physical or chemical cross-linking taking place between synthetic polymers or biopolymers through different functional groups like sulphonic (-HSO3), amino (-NH2), hydroxyl (-OH), and carboxyl (-COOH). In nanogels, the cross-linked polymers consist of amphiphilic or hydrophilic macromolecular chains which swell by holding the higher volume of water and maintain the structure intact without dissolving into the aqueous medium. 3 The capacity to absorb the water to a greater extent is due to the macromolecular chains and hydrophilic functional group present in the structure of the polymer. 4 The physiochemical interactions between the functional group of polymeric compounds and drug substances are responsible for the drug loading of nanogels which can host drug molecules in their polymeric network. 5 Owing to the nanogel properties, it carries several drugs to numerous organs. Nanogels are crucial in a variety of sectors, including organ targeting, gene delivery, diagnostics, and chemotherapy. 6,7 Biopolymer-based nanogels play a crucial role in drug delivery and tissue engineering applications. 8,9 These contain all the properties of synthetic counterparts and the added intrinsic properties such as biodegradability, and abundance in nature, are non-