Polysaccharides possess great potential advantages in the development of drug delivery vehiclesrndue to their biocompatibility, biodegradability, and amenability for modifications. Cellulose, arnwell-known ubiquitous polysaccharide on Earth, and its derivatives are among the most promisingrnand versatile materials with special chemical structure providing a good platform for the synthesisrnof hydrogel networks. Woody plants and cotton are the major sources of cellulose and itsrnderivatives such as cellulose nanocrystals (CNCs) and carboxymethyl cellulose (CMC), butrnoverutilization of these sources has raised huge economic and environmental concerns forcingrnresearchers and stakeholders to look for other potential substitutes. Nanogels, three-dimensionalrnhydrogel nanomaterials, based on natural biodegradable polymers have recently got considerablernattention as effective drug delivery nanocarriers as they include the advantages of hydrogels andrnnanoparticles. However, the longer preparation time and usage of large amounts of organicrnsolvents and surfactants have limited their applications. rnThe objectives of this study were to explore teff straw (TS), enset fiber (EF), sugarcane bagassern(SB) and coffee hull (CH) as alternative sources of cellulose, CNCs and CMC as well as to preparernnanocellulose-based nanogels following a simple and green ecofriendly approach, and evaluaternthe nanogels for sustained delivery of various model BCS class drugs: acyclovir, carbamazepinernand furosemide. rnCellulose fibers were extracted from the aforementioned lignocellulosic sources following variousrneco-friendly chlorine-free extraction conditions comprising alkaline pretreatment, delignificationrn(using formic acid, acetic acid and hydrogen peroxide) and bleaching (using alkaline hydrogenrnperoxide) to obtain an optimum condition. CNCs were obtained following sulfuric acid (64% w/w)rnhydrolysis of cellulose fibers extracted using 5%, 10% and 17.5% sodium hydroxide at thernpretreatment stage. CMC was obtained from the as-extracted cellulose fibers, following mercerization and etherification steps using sodium hydroxide and monochloroacetic acid inrnisopropyl alcohol. The as-obtained cellulose fibers, CNCs and CMC were investigated andrncharacterized in terms of yield, crystallinity, chemical functionality, morphology, particlerndiameter/size, and thermal stability. rnEF yielded the highest cellulose content (60.0%), whereas CH the least (35.5%). FTIR spectra andrnSEM morphological studies of the celluloses indicated progressive removal of non-cellulosicrnconstituents. XRD analyses showed EF cellulose had the highest crystallinity index (CrI)rn(85.56%), crystallite size (5.52 nm), and proportion of crystallite interior chains of 200 planern(0.629), exhibiting unique physicochemical properties. TGA studies revealed enhanced stabilityrnof the as-extracted celluloses. All as-isolated cellulose fibers and CNCs maintained a typicalrnCellulose IÎ²rn crystalline structure, but Cellulose I and II allomorphs coexisted in CNCs rnisolatedrnfrom TS, EF, and SB pretreated with 17.5% sodium hydroxide. The highest yield (~ 70%), CrI (~rn86%), and crystal size (~ 6 nm) were observed in EFâ€“CNCs, and the least in CHâ€“CNCs (yield:rn~25%, crystal size: ~4 nm) and SB-CNCs (CrI: ~65.4%). FTIR spectra of all CNCs indicatedrntypical chemical composition of cellulose. TEM analyses revealed that CNCs rnisolated from allrnbyproducts pretreated with 5% sodium hydroxide had higher aspect ratios (17.32-36.67) withrnelongated needle-shaped nanoscale structures than CNCs obtained with 17.5% sodium hydroxidernat the pretreatment stage (8.95-16.38). The thermal studies by TGA/DTG revealed the CNCs hadrna two-step decomposition process at Tmaxrn ranging from 215â€“225 Â°C and 340â€“355 Â°C. The CNCs rnobtained using 5% sodium hydroxide at the pretreatment stage also exhibited high yield, crystalrnsize, crystallinity, length, aspect ratio and colloidal stability. The high alkaline condition, 17.5%rnsodium hydroxide, might not necessarily contribute to the polymorphic transition in lignocellulosicrnmaterials with higher lignin content as evidenced in CH. By and large, the formation of CellulosernI and II allomorphs in the as-obtained CNCs were dependent on the cellulose source and cellulosernextraction condition, and less influenced by sulfuric acid hydrolysis. The as-obtained CMC fromrnall plant sources had DS in the range of 0.71â€1.18, and with a yield of 1.28â€1.55 g/g. Thernappearance of new bands around 1600 and 1412 cmrnâ€1rn in the FTIR spectra of asâ€obtained CMCrnshowed efficient attachment of carboxymethyl groups to the cellulose chains. The XRD analysesrnof the asâ€obtained CMC samples showed a significant reduction in crystallinity with the mainrndiffraction signal at 2Î¸=20Â°, showing polymorphic transition to Cellulose II too. From the TGArnresults, the Tmaxrn of the asâ€obtained CMC ranged from 285â€296 Â°C. The SEM results indicated that rnthe CMC samples existed as more granular and corroded structure. At similar modificationrncondition, CMC obtained from EF had the highest DS, %carboxymethyl, yield and purity. rnBased on its unique and superior properties such as yield, purity, and crystallinity, EF was selectedrnfor preparation of carboxymethyl (nano)cellulose (CM(N)C) to be included as anionicrnpolysaccharide in the nanogel formulations. CMNC was obtained from EF-CNCs following arnsimilar etherification approach for CMC. The DS and yield of EF-CMNC were 0.56 and 1.11 g/g. rnThe nanogels were prepared from self-assembled anionic CMC- or CMNC- and cationic-lysozymernblends via electrostatic complexation for sustained drug delivery. Three model drugs fromrndifferent classes of Biopharmaceutics Classification System (BCS): acyclovir (BCS III),rncarbamazepine (BCS II), and furosemide (BCS IV) were evaluated. The influence of weight ratiosrnof CMNC-lysozyme, pH, sonication and heating times, and storage conditions on the size andrnpolydispersity index (PDI) of the nanogels was studied. The nanogels were characterized by PCS,rnUV/Vis spectrophotometry, FTIR spectroscopy, TEM, XRD, TGA, and DSC techniques, and alsornevaluated for drug loading and in vitro drug release. Spherical nanogels of small sizes (75-110 nm)rnand PDI (< 0.2) as well as large zeta potential (-38 to -55 mV) were prepared at optimal conditionrn(at 1:1 weight ratio of CMNC:lysozyme, pH 7.4, and 30-min heating time). CMNC-based nanogelsrnexhibited lower particle size than CMC-based nanogels at all pH points (5.3-10.5) investigated.rnThe results demonstrated high encapsulation efficiency (62-94%) and loading capacity (18-27%),rnand sustained release profiles of the model drugs from the loaded nanogels for 12 h. rnOn the basis of the physicochemical characteristics, all the byproducts studied could be consideredrnas alternative sources of cellulose, CNCs, and CMC for potential value-added industrialrnapplications although differences were observed due to variations in cellulose sources. EF showedrnunique and superior physicochemical properties. From the findings, nanocellulose-based nanogelsrnwith potential applications as sustained release nanocarriers for various BCS class drugs wererndeveloped following a simple and green approach.