Advancements in Hybrid Cellulose-Based Films: Innovations and Applications in 2D Nano-Delivery Systems.

This review paper delves into the realm of hybrid cellulose-based materials and their applications in 2D nano-delivery systems. Cellulose, recognized for its biocompatibility, versatility, and renewability, serves as the core matrix for these nanomaterials. The paper offers a comprehensive overview of the latest advancements in the creation, analysis, and application of these materials, emphasizing their significance in nanotechnology and biomedical domains. It further illuminates the integration of nanomaterials and advanced synthesis techniques that have significantly improved the mechanical, chemical, and biological properties of hybrid cellulose-based materials.

Cations and Anions Affect the Speed of Sound in Water Oppositely.

Identifying the composition of a solution using acoustics remains a challenge. It is known that for low salt concentrations the speed of sound in water increases linearly with the concentration of the electrolyte, but the contribution of individual cations and anions is unknown. We introduce the concept of intrinsic sound speed Ai to quantify the contribution of ions to the speed of sound. We found that cations increase the speed of sound in water whereas anions decrease the speed of sound. Hydration layers around the ions play a major role. Because cations have a hydration layer thicker than that of anions, their contribution to the speed of sound is larger than that of anions. Experimental data on salts not used to determine the contribution of individual ions are in quantitative agreement with the predicted values. Our method can be applied to various systems containing small quantities of ions, molecules, or particles. With the knowledge that cations increase the speed of sound, we were able to explain previously unexplained data in the literature.

Multifunctional self-healing hydrogels via nanoengineering of colloidal and polymeric cellulose.

The unique features of self-healing hydrogels hold great potential for biomedical applications including injectable hydrogels for cancer treatment, procedures for tumor removal or resection. However, the fabrication of durable and multifunctional self-healing hydrogels composed of biocompatible, green building blocks via versatile synthetic methodology continues to pose a significant challenge. Here, we engineered dialdehyde cellulose (DAC, as a macromolecular bio-crosslinker), and electrosterically stabilized nanocrystalline cellulose (ENCC, as a ligand-targeted drug carrier) to facilitate a strategy for the construction of self-healing hydrogels. Benefiting from its high carboxyl group density, ENCC was functionalized with folic acid (FA) using a non-toxic DMTMM coupling agent and loaded with doxorubicin (DOX, a model drug) through electrostatic interactions. A natural self-healing hydrogel was prepared from carboxymethyl chitosan (CCTS) and DAC mixed with DOX-loaded FA-ENCC using dynamic Schiff-base and hydrogen linkages. A combination of active supramolecular and vital covalent junctions led to a soft (storage modulus ∼500 Pa) and durable material, with rapid (< 5 min) reconstruction of molecular structure from fractured and injected to intact forms. The DAC-CCTS hydrogel showed an appreciable loading capacity of ∼5 mg g-1. Biocompatibility of the hydrogels was evaluated using cell viability and metabolic activity assays, showing lower metabolic activity due to sustained release of its cargo. These materials offer a versatile, sustainable, and green platform for the efficient construction of hydrogels, based on macro- and nano-engineered cellulose, the most abundant and easily accessible biopolymer.

Ultrathin ultrastrong transparent films made from regenerated cellulose and epichlorohydrin.

Thin films used in electronic devices are often petroleum-based, non-biodegradable, and non-renewable polymers. Herein, ultrathin ultrastrong regenerated cellulose films were made with a facile method by applying a solution of mildly carboxylated nanocellulose and various amounts of epichlorohydrin (ECH) as a crosslinker. The morphology and physiochemical properties of films were measured using FE-SEM, TEM, FTIR, NMR, UV-Vis, XRD, DLS, and TGA. Carboxylated cellulose with a charge content of 1.5 mmol/g was prepared to make alkaline dopes containing nanocrystalline cellulose (CNC). Then, ECH (0-50%) was added and the dope was blade cast, dried in an oven, regenerated in an acid bath, washed, and air dried to make uniform films approximately 1 µm thick. The tensile stress and elastic modulus of the films were measured and found to be 100-300 MPa and 5-12.7 GPa, respectively. Higher amounts of ECH led to stronger films. All films were over 96% transparent, insoluble in water, and absorbed 24-28% moisture. TGA analysis showed ultrathin films were thermally resistant up to 250 °C and were stable and unchanged over a month at 105 °C showing excellent thermal aging resistance. Overall, films with 5-10% ECH are extremely strong, which makes them promising bioresource-based candidates for flexible electronic applications.

Internally bridged nanosilica for loadings and release of sparsely soluble compounds.

The engineering of a new monodisperse colloid with a sea urchin-like structure with a large complex internal structure is reported, in which silica surfaces are bridged by an aromatic organic cross-linker to serve as a nanocarrier host for drugs such as doxorubicin (DOX) against breast cancer cells. While dendritic fibrous nanosilica (DFNS) was employed and we do not observe a dendritic structure, these particles are referred to as sea urchin-like nanostructured silica (SNS). Since the structure of SNS consists of many silica fibrils protruding from the core, similar to the hairs of a sea urchin. For the aromatic structured cross-linker, bis(propyliminomethyl)benzene (b(PIM)B-S or silanated terephtaldehyde) were employed, which are prepared with terephtaldehyde and 3-aminopropyltriethoxy-silane (APTES) through a simple Schiff base reaction. b(PIM)B-S bridges were introduced into SNS under open vessel reflux conditions. SPS refers to the product obtained by incorporating the cross-linker b(PIM)B-S in ultra-small colloidal SNS particles. In-situ incorporation of DOX molecules resulted in SPS-DOX. The pH-responsive SPS nanocomposites were tested as biocompatible nanocarriers for controllable doxorubicin (DOX) delivery. We conclude that SPS is a unique colloid which has promising potential for technological applications such as advanced drug delivery systems, wastewater remediation and as a catalyst for green organic reactions in water.

Adsorption of Tannic Acid onto Gold Surfaces.

Thin film coatings are widely applicable in materials for consumer products, electronics, optical coatings, and even biomedical applications. Wet coating can be an effective method to obtain thin films of functional materials, and this technique has recently been studied in depth for the formation of bioinspired polyphenolic films. Naturally occurring polyphenols such as tannic acid (TA) have garnered interest due to their roles in biological processes and their applicability as antioxidants, antibacterial agents, and corrosion inhibitors. Understanding the adsorption of polyphenols to surfaces is a core aspect in the fabrication processes of thin films of these materials. In this work, the adsorption of TA to gold surfaces is measured using a quartz crystal microbalance with dissipation monitoring (QCMD) and surface plasmon resonance (SPR) for a wide range of TA concentrations. The adsorption kinetics, aggregation, and stability of TA solutions in physiological-like conditions are studied. Unexpectedly, it is found that the adsorption rates depend only weakly on concentration because of the presence of TA aggregates that do not adsorb. The mechanism of layer formation is also investigated, finding that TA monolayers readily adsorb onto gold with flat or edge-on molecular orientations dependent on the solution concentration. A mix of orientations in the intermediate case leads to slow multilayer adsorption.

Antibacterial Pickering emulsions stabilized by bifunctional hairy nanocellulose.

HYPOTHESIS: Pickering emulsions, defined as emulsions that are stabilized by colloidal particles, provide dispersion stability by preventing coalescence of the dispersed phase. In this study, we used a bifunctional hairy nanocellulose (BHNC) bearing both aldehyde and carboxylic acid groups as an stabilizer. We hypothesize that these particles as Pickering stabilizers can effectively reside at the oil-water interface, better than hairy nanocelluloses containing only carboxyl groups or aldehyde groups, and provide long-term stability without the need of any surfactants. EXPERIMENTS: Varying concentrations of BHNC were tested to explore the optimal concentration that provides emulsion stability. The effects of various preparation conditions such as salt and pH were also studied. Finally, carvacrol, an antibacterial essential oil, was loaded in the oil phase to develop antibacterial emulsions. FINDINGS: It was shown that a 1% BHNC suspension provides 90% and 80% stability for a duration of 30 and 60 days, respectively. A theoretical model using nuclear magnetic resonance relaxometry data is developed to prove that only a monolayer of BHNC covers oil droplets. Increasing the concentration of BHNC decreased the size of oil droplets, which as a result increases the surface area available for monolayer coverage. It was also shown that the antibacterial emulsions are highly effective against Gram-negative (i.e. E. coli) and Gram-positive (i.e. S. aureus) bacteria. Accordingly, BHNC as a highly functionalized bio-derived colloidal particle opens new opportunities for engineering highly stable Pickering emulsions.

Hairy Nanocellulose-Based Supramolecular Architectures for Sustained Drug Release.

The engineering of a new type of trifunctional biopolymer-based nanosponges polymerized by cross-linking beta-cyclodextrin ethylene diamine (ßCD-EDA) with bifunctional hairy nanocellulose (BHNC) is reported herein. We refer to the highly cross-linked polymerized BHNC-ßCD-EDA network as BBE. ßCD-EDA and BHNC were cross-linked at various ratios with the help of DMTMM (4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium) as a green activator in deionized water as a solvent, which resulted in different morphological shapes of BBE. Some of these structures were chiral due to cross-linked liquid crystalline structures. A comprehensive characterization study was done to show their unique morphological, structural, and dimensional properties of BBEs. Moreover, to further investigate and to confirm the surface modification of the precursors and final BBE structures, Fourier transform infrared and nuclear magnetic resonance spectroscopy, thermogravimetric analysis, Brunauer-Emmett-Teller analysis, and X-ray diffraction were applied. The hairy nanocellulose particles were considered as the backbone, and the immobilized cyclodextrin cavities can capture doxorubicin, which was used as a model drug molecule via host-guest inclusion complexation. Finally, the obtained BBE networks showed different and sustained drug release profiles and pH responsiveness. BBE biopolymers were tested as biocompatible nanocarriers for controlled release. We realize that these structures are too big for anti-cancer drug delivery by injection or oral intake, but these structures have a high potential to be applied in wound dressing and implants. They could also be used for capturing antibiotics, dyes, and organic compounds from wastewater.

Advancement in Biosensor Technologies of 2D MaterialIntegrated with Cellulose-Physical Properties.

This review paper provides an in-depth analysis of recent advancements in integrating two-dimensional (2D) materials with cellulose to enhance biosensing technology. The incorporation of 2D materials such as graphene and transition metal dichalcogenides, along with nanocellulose, improves the sensitivity, stability, and flexibility of biosensors. Practical applications of these advanced biosensors are explored in fields like medical diagnostics and environmental monitoring. This innovative approach is driving research opportunities and expanding the possibilities for diverse applications in this rapidly evolving field.

Synthesis and characterization of hairy aminated nanocrystalline cellulose.

HYPOTHESIS: The synthesis and characterization of aminated nanocrystalline cellulose (ANCC), a new member of the hairy nanocellulose family, is reported. Hairy nanocelluloses consist of a crystalline rod-like body with amorphous cellulose chains ("hairs") at both ends, on which various functional groups can be accommodated. In ANCC these groups are reactive primary amine groups, which are useful for bioconjugation- and Schiff base-centered modifications. We hypothesize that a two-step oxidation-reductive amination of cellulose fibers followed by hydrothermal treatment will result in the formation of rod-like hairy ANCC. EXPERIMENTS: ANCC was prepared by converting the aldehyde groups in cellulose, introduced by a periodate oxidation, to primary amines using ammonia and sodium borohydride, followed by a hot water treatment, during which diamine modified cellulose fibers were converted to ANCC. ANCC was characterized by AFM, TEM, DLS, ELS, FTIR, NMR, XPS and conductometric titration. Antibacterial activity of ANCC was assessed by the viable cell counting method. FINDINGS: ANCC, with an amine content of 5.5 mmol g-1 is a bare nanocolloid (i.e. non-coated, without adsorbed polyelectrolytes or surfactants) which, as far as we know, has a positive charge density larger than any other bare cationic nanocolloid. It was observed that ANCC particles have a needle-like morphology with a width of ~ 5 nm and a length ~ 120 nm. DLS results proof that ANCC is hairy. Spectroscopic analysis confirmed the introduction of surface primary amine groups. ANCC showed promising bactericidal activities, against Gram-negative species due to their thinner and penetrable cell wall.

Dendritic Fibrous Colloidal Silica Internally Cross-linked by Bivalent Organic Cations: An Efficient Support for Dye Removal and the Reduction of Nitrobenzene Derivatives.

We designed a new unique amphoteric monodisperse colloid with a large complex internal structure, in which silica surfaces are bridged with an organic cross-linker. The rationale was that such colloids would be excellent adsorbents for cationic and anionic dyes and, when doped with noble metal nanoparticles, would be an excellent catalyst for the reduction of a variety of organic compounds. In the first step, the organo-silica bridging agent (bivalent organic cross-linkers) DABCO-S (silanated DABCO) was prepared through a simple nucleophilic substitution reaction between (3-chloropropyl)triethoxysilane and bivalent 1,4-diazabicyclo[2.2.2]octane (DABCO) (a strong base). In the second step, a DABCO-S bridge was introduced into dendritic fibrous nanostructured colloidal silica (DFNS) under open-vessel reflux conditions. We refer to the product obtained by incorporating DABCO-S in DFNS as DDS. The unique characteristics of DFNS are completely preserved in this new type of periodic mesoporous organo-silica-DFNS. The produced nanocomposite has a high surface area of about 807 m2 g-1, a large pore volume of 1.9 cm3 g-1, and a bimodal pore size distribution, with small 2.5 nm pores and large 30 nm pores. As such, DDS is an efficient adsorbent for dye removal from wastewater. The results show that DDS can adsorb positive and negative dyes such as methylene blue, orange II sodium salt (OR), and procion red mx-58 (PR) with a capacity of 678, 3192, and 3190 mg dye/g adsorbent. Introducing silver nanoparticles in situ into DDS leads to a composite with excellent accessibility of reactants to the Ag surface, resulting in an efficient catalytic reduction of nitro aromatic compounds (NACs) in aqueous media.

Polyphenol-Peptide Interactions in Mitigation of Alzheimer's Disease: Role of Biosurface-Induced Aggregation.

Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder, responsible for nearly two-thirds of all dementia cases. In this review, we report the potential AD treatment strategies focusing on natural polyphenol molecules (green chemistry) and more specifically on the inhibition of polyphenol-induced amyloid aggregation/disaggregation pathways: in bulk and on biosurfaces. We discuss how these pathways can potentially alter the structure at the early stages of AD, hence delaying the aggregation of amyloid-ß (Aß) and tau. We also discuss multidisciplinary approaches, combining experimental and modelling methods, that can better characterize the biochemical and biophysical interactions between proteins and phenolic ligands. In addition to the surface-induced aggregation, which can occur on surfaces where protein can interact with other proteins and polyphenols, we suggest a new concept referred as "confinement stability". Here, on the contrary, the adsorption of Aß and tau on biosurfaces other than Aß- and tau-fibrils, e.g., red blood cells, can lead to confinement stability that minimizes the aggregation of Aß and tau. Overall, these mechanisms may participate directly or indirectly in mitigating neurodegenerative diseases, by preventing protein self-association, slowing down the aggregation processes, and delaying the progression of AD.

Biotemplated Hollow Mesoporous Silica Particles as Efficient Carriers for Drug Delivery.

We designed three types of hollow-shaped porous silica materials via a three-step biotemplate-directed method: porous hollow silica nanorods, hollow dendritic fibrous nanostructured silica (DFNS), and ultraporous sponge-like DFNS. The first step was making a biotemplate, for which we used cellulose nanocrystals (CNCs), consisting of rod-shaped nanoparticles synthesized by conventional acid hydrolysis of cellulose fibers. In a second step, core-shell samples were prepared using CNC particles as hard template by two procedures. In the first one, core-shell CNC-silica nanoparticles were synthesized by a polycondensation reaction, which exclusively took place at the surface of the CNCs. In the second procedure, a typical synthesis of DFNS was conducted in a bicontinuous microemulsion with the assistance of additives. DFNS was assembled on the surface of the CNCs, giving rise to core-shell CNC-DFNS structures. Finally, all of the silica-coated CNC composites were calcined, during which the CNC was removed from the core and hollow structures were formed. These materials are very lightweight and highly porous. All three structures were tested as nanocarriers for drug delivery and absorbents for dye removal applications. Dye removal results showed that they can adsorb methylene blue efficiently, with ultraporous sponge-like DFNS showing the highest adsorption capacity, followed by hollow DFNS and hollow silica nanorods. Furthermore, breast cancer cells show a lower cell viability when exposed to doxorubicin-loaded hollow silica nanorods compared with control or doxorubicin cultures, suggesting that the loaded nanorod has a greater anticancer effect than free doxorubicin.

Cellulose-based dispersants and flocculants.

Natural dispersants and flocculants, often referred to as dispersion stabilizers and liquid-solid separators, respectively, have secured a promising role in the bioprocessing community. They have various applications, including in biomedicine and in environmental remediation. A large fraction of existing dispersants and flocculants are synthesized from non-safe chemical compounds such as polyacrylamide and surfactants. Despite numerous advantages of synthetic dispersants and flocculants, issues such as renewability, sustainability, biocompatibility, and cost efficiency have shifted attention towards natural homologues, in particular, cellulose-based ones. Within the past decade, cellulose derivatives, obtained via chemical and mechanical treatments of cellulose fibrils, have successfully been used for these purposes. In this review article, by dividing the functional cellulosic compounds into "polymeric" and "nanoscale" categories, we provide insight into the engineering pathways, the structural frameworks, and surface chemistry of these "green" types of dispersants and flocculants. A summary of their efficiency and the controlling parameters is also accompanied by recent advances in their applications in each section. We are confident that the emergence of cellulose-based dispersing and flocculating agents will extend the boundaries of sustainable green technology.

Hybrid Aerogel Nanocomposite of Dendritic Colloidal Silica and Hairy Nanocellulose: an Effective Dye Adsorbent.

In this study, a new type of silica-cellulose hybrid aerogel was synthesized through a green and facile chemical cross-linking process. In a first step, dendritic fibrous nanostructured (colloidal) silica particles (DFNS) were prepared by a simple hydrothermal technique. Then, the surface of DFNS particles was functionalized with amine groups using 3-aminopropyltriethoxysilane to produce DFNS-NH2. In a second step, bifunctional hairy nanocellulose (BHNC) particles were functionalized with both aldehyde and carboxylic groups. The aldehyde groups of BHNC and the amine groups of DFNS-NH2 chemically reacted through a Schiff base reaction to form a hybrid hydrogel nanocomposite. Therefore, no external cross-linker is required in the synthesis. This hybrid aerogel is very lightweight and highly porous with a density of 0.107 g mL-1 and a porosity of 93.0 ± 0.4%. It has a large surface area of 350 m2 g-1, a large pore volume of 0.23 cm3 g-1, and a small pore size of 3.9 nm. The developed aerogel contains both positively and negatively charged functional groups and is a highly efficient substrate for dye adsorption from water, for both cationic and anionic organic dyes. These aerogels were found to have an outstanding adsorption capacity toward methylene blue (MB) as a cationic dye and methyl orange (MO) as an anionic dye. The results show that the aerogels can adsorb MB and MO with a capacity of 270 and 300 mg dye/g adsorbent, respectively.

Highly Absorbent Antibacterial and Biofilm-Disrupting Hydrogels from Cellulose for Wound Dressing Applications.

In this study, a carboxyl-modified cellulosic hydrogel was developed as the base material for wound dressings. ε-poly-l-lysine, a natural polyamide, was then covalently linked to the hydrogel through a bioconjugation reaction, which was confirmed by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR). The antibacterial efficacy of the hydrogel was tested against two model bacteria, Staphylococcus aureus and Pseudomonas aeruginosa, two of the most commonly found bacteria in wound infections. Bacterial viability and biofilm formation after exposure of bacteria to the hydrogels were used as efficacy indicators. Live/Dead assay was used to measure the number of compromised bacteria using a confocal laser scanning microscope. The results show that the antibacterial hydrogel was able to kill approximately 99% of the exposed bacteria after 3 h of exposure. In addition, NIH/3T3 fibroblasts were used to study the biocompatibility of the developed hydrogels. Water-soluble tetrazolium salt (WST)-1 assay was used to measure the metabolic activity of the cells and Live/Dead assay was used to measure the viability of the cells after 24, 48, and 72 h. The developed antibacterial hydrogels are light weight, have a high water-uptake capacity, and show high biocompatibility with the model mammalian cells, which make them a promising candidate to be used for wound dressing applications.

Carboxylated Cellulose Nanocrystals Developed by Cu-Assisted H2O2 Oxidation as Green Nanocarriers for Efficient Lysozyme Immobilization.

Cellulose nanocrystals (CNCs), having a high specific surface area and versatile surface chemistry, provide considerable potential to interact by various mechanisms with enzymes for nano-immobilization purposes. However, engineering chemically safe CNCs, suitable for edible administrations, presents a significant challenge. A reliable carboxylate form of H-CNCs was formed using H2O2 oxidation of softwood pulp under mild thermal conditions. Negatively charged carboxyl groups (∼0.9 mmol g-1) played a key role in lysozyme immobilization via electrostatic interactions and covalent linkages, as evidenced by Fourier transform infrared and 13C cross-polarization magic angle spinning nuclear magnetic resonance spectroscopies. Adsorption isotherms showed a high loading capacity of H-CNCs (∼240 mg g-1), and fitting the data to the Langmuir model confirmed monolayer coverage of lysozyme on their surface. Using a non-toxic coupling agent, 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride, lysozyme-conjugated H-CNCs were developed with an immobilization yield of ∼65% and relative catalytic activity of ∼60%, similar to lysozyme adsorption on H-CNCs. These H-CNC-lysozyme nanohybrids, rationally processed via safe and green strategies, are specifically exploitable as catalytically active emulsifiers in food and pharmaceutical sectors.

A Review on Surface-Functionalized Cellulosic Nanostructures as Biocompatible Antibacterial Materials.

As the most abundant biopolymer on the earth, cellulose has recently gained significant attention in the development of antibacterial biomaterials. Biodegradability, renewability, strong mechanical properties, tunable aspect ratio, and low density offer tremendous possibilities for the use of cellulose in various fields. Owing to the high number of reactive groups (i.e., hydroxyl groups) on the cellulose surface, it can be readily functionalized with various functional groups, such as aldehydes, carboxylic acids, and amines, leading to diverse properties. In addition, the ease of surface modification of cellulose expands the range of compounds which can be grafted onto its structure, such as proteins, polymers, metal nanoparticles, and antibiotics. There are many studies in which cellulose nano-/microfibrils and nanocrystals are used as a support for antibacterial agents. However, little is known about the relationship between cellulose chemical surface modification and its antibacterial activity or biocompatibility. In this study, we have summarized various techniques for surface modifications of cellulose nanostructures and its derivatives along with their antibacterial and biocompatibility behavior to develop non-leaching and durable antibacterial materials. Despite the high effectiveness of surface-modified cellulosic antibacterial materials, more studies on their mechanism of action, the relationship between their properties and their effectivity, and more in vivo studies are required.

Dye Removal Using Hairy Nanocellulose: Experimental and Theoretical Investigations.

Adsorption is a common technique for the treatment of dye-contaminated wastewater. Achieving a high dye removal capacity is a common challenge with sustainable, low-cost adsorbents. Recently, a class of easily functionalized, biorenewable cellulose nanoparticles called hairy nanocellulose has been developed. Electrosterically stabilized nanocrystalline cellulose (ENCC), which can be synthesized from wood pulp through a two-step oxidation by periodate and chlorite, is a form of hairy nanocellulose with a high negative charge density, and thus has the potential for a high adsorption capacity. In this work, the adsorption of methylene blue, a cationic dye, by ENCC was shown to occur up to charge stoichiometry (1400 mg dye/g adsorbent), at which point aggregation of ENCC-dye complexes is observed. A model is developed to show that the adsorption can be described by an ion-exchange mechanism and is influenced by the presence of other ions. Equilibrium dye removal is reduced at both high ionic strengths and low pH. To facilitate handling, composite hydrogel beads of sodium alginate and ENCC (ALG-ENCC beads) are developed, and their methylene blue removal capacity is shown to maintain a high removal capacity (1250 mg/g). ALG-ENCC beads provide a facile way to employ these nanoparticles on a larger scale, providing a potential means for the removal of dyes and other contaminants at larger wastewater volumes.

Stimuli-responsive chitosan as an advantageous platform for efficient delivery of bioactive agents.

Despite a diverse range of active pharmaceutical agents currently at our disposal, high morbidity rate diseases continue to pose a major health crisis globally. One of the important parameters in this regard is the controlled cargo delivery at desired sites. Among a variety of synthetic and natural macromolecular systems, chitosan, an abundant biopolymer, offers a platform for tailored architectures that could have high loading capacity of cargo, target and deliver. Stimuli directed accumulation of vehicles and drug release is an area of direct relevance to biomedical applications. In this review, we highlight essential characteristics of modified chitosan that present themselves for efficient response through an internal (glutathione, reactive oxygen species, pH, temperature, enzymes, and chemical/electrical potential gradient), and external stimuli (ultrasound, light, mechanical stimuli, magnetic and electrical fields). With a brief review of the pertinent properties of chitosan that are relevant to biology, the design and critical evaluation of varied chitosan-based platforms is discussed. Future directions in exploiting important features of chitosan in this area can be derived from the presented comparative evaluation of the current literature in drug delivery.