# Novel Chitosan Derivatives and Their Multifaceted Biological Applications
## 3 Biological Applications of ChDs
### Miscellaneous Bio-Applications  
N,O-selenized N-(2-carboxyethyl) chitosan (sNCCS) was synthesized through carboxethylation and selenylation. In vitro assessment confirmed that sNCCS has excellent bile acid binding capacity. Moreover, higher selenium content significantly enhanced the antioxidant properties of the sNCCS. No cytotoxic effect was observed on Caco-2 cells [115]. Novel water soluble phosphonium ChDs (WSPCSs) with two different degrees of substitution (3.6% and 4.2%) of quaternary phosphonium were synthesized in a homogeneous system. The derivatives could be easily dissolved in water. MTT (methylthiazolyltetrazolium) assay indicated that they had low cytotoxicity to L929 cells [119]. The pharmaceutical performance of an innovative chitosan derivative, methyl acrylate chitosan-bearing p-nitrobenzaldehyde (MA*CS*pNBA) Schiff base, was studied by [PERSON] et al. [71]. The antibacterial activity of MA*CS*pNBA was used against multi-drug resistant (MDR) Gram-negative and Gram-positive bacteria. It also exhibited anti-biofilm, antioxidant and anti-inflammatory biomaterial, evidencing hemocompatibility and no cytotoxicity [71]. N-substituted ChDs were synthesized via condensation with a number of selected aryl and heteroaryl aldehydes. The antimicrobial activity of chitosan Schiff's base (CSB) derivatives was confirmed against four types of bacteria, and two crop-threatening pathogenic fungi. The triazolo-Schiff's base derivative 3c was tested against human breast adenocarcinoma cells (MCF-7), human colon carcinoma cells (HCT-116), and human hepatocellular liver carcinoma cells (HepG-2), showed growth inhibitory effects [64]. A series of N,N,N-trimethyl-O-(ureidopyridinium)acetyl ChDs were synthesized. This modification developed the water solubility and biological properties of chitosan. The prepared ChDs exhibited improved antioxidant activity compared to chitosan. The ChDs also showed anti-fungal activity on _Phomopsis asparagus_ as well as _Botrytis cinerea_, and they showed significant inhibitory effect on the selected phytopathogen as well as low cell toxicity [108]. In another study, Schiff bases of chitosan (CS) were synthesized using citronellal, citral, containing selenium and sulfur. Biological assays were conducted using films prepared by blending ChDs and poly(vinyl alcohol). The film inhibited _Escherichia coli_, _Staphylococcus aureus_ and _Candida albicans_. In vivo assays revealed that the ChDs film attenuates atopic dermatitis-like symptoms in mice, by suppressing the increase in myeloperoxidase (MPO) activity and reactive species (RS) levels induced by 2,4-dinitrochlorobenzene (DNCB), indicative of the potent use of ChDs in skin infection treatments [73]. The ChDs modified with poly(ethylene glycol) (PEG) were soluble in neutral water, interacted with acrylic polymer having carboxy groups and gave a more stable emulsion. The N-carboxymethylylated, N,O-sulfated, and N-trimethylated ChDs showed reasonable low electric resistance. Carbohydrate-branched ChDs were synthesized to obtain increased water solubility and attain novel biological properties. The specific interaction with lectins or bacterium and the activation of canine polymorpho nuclear leukocyte (PMN) cells were biological activities made possible by the synthesized carbohydrate-branched ChDs [126]. Chitosan with phenolic hydroxyl groups (Chit-Ph), were soluble at neutral pH and gellable via a peroxidase catalyzed reaction within seconds and compatible with I929 cells [117]. Soluble, antibacterial ChDs were prepared by [PERSON] et al. via region selective chemical modification. Water-solubility increased and the results of the platelet adhesion and the activated partial thromboplastin time (APTTs) assays indicate that grafting hydroxyethyl could improve anticoagulation of chitosan. The antibacterial activity of HC against Enterococcus and _E. coli_ was also demonstrated [57].