Hydrophilic Chitosan Derivatives: Synthesis and Applications

Abstract

Polymer alternatives sourced from nature have attracted increasing attention for applications in medicine, cosmetics, agriculture, food, water purification, and more. Among them, chitosan is the most versatile due to its full biodegradability, exceptional biocompatibility, multipurpose bioactivity, and low toxicity. Although remarkable progress has been made in its synthetic modification by using C3/C6 secondary/primary hydroxy (-OH) and the C2 amino (-NH₂ ) active sites, its solubility under physiological conditions remains limited and has hampered larger-scale adoption. This review summarizes different synthetic methods that increase chitosan's hydrophilicity and water solubility by using covalent modifications, namely amino acid addition, quaternary ammonium formation, phosphorylation, and carboxymethylation. We also review several applications for each type of substitution in fields such as cosmetics, medicine, agriculture, and water purification, and provide an outlook and perspective for future modifications and implementations.

Keywords: antibacterial; biopolymers; chitosan; hydrophilic substitution; nanoparticles.

Scheme 1

Esterification reaction of chitosan with l‐alanine.

Scheme 2

Selective amidation of chitosan with l‐arginine/l‐cysteine/l‐histidine.

Scheme 3

l‐Histidine epichlorohydrin activation followed by chitosan etherification.

Scheme 4

Preparation of quaternary ammonium chitosan polymers by using CH₃I.

Scheme 5

Synthesis of quaternary ammonium chitosan polymers by using GTA.

Scheme 6

Synthesis of quaternary ammonium on chitosan‘s C6−OH.

Scheme 7

Synthetic routes for chitosan phosphorylation.

Scheme 8

Chitosan phosphorylation with phosphoric acid and formaldehyde.

Scheme 9

Exhaustive phosphorylation of chitosan by using gas‐phase PCl₃.

Scheme 10

Chitosan carboxymethylation derivatives.[ ³⁶ , ³⁷ , ³⁸ , ³⁹ , ⁴⁰ ]

Figure 1

Chitosan‐arginine membrane characterization. A) Macroscopic image of the produced membrane. Analysis of B) membrane porosity and C) membrane surface contact angle. D) Membrane fiber diameter distribution. Reprinted with permission from ref. . Copyright: 2015, Elsevier.

Scheme 11

Schiff base derivatives of HACC amino acids.

Figure 2

Adsorption kinetics of histidine‐modified chitosan beads at 25 °C, pH 5, and a copper(II) nitrate concentration of 0.47 mmol L⁻¹. Reprinted with permission from ref. . Copyright: 2021, Elsevier.

Figure 3

synthesis, application methods, and antibacterial as well as antifungal activity of QAC derivatives. Reprinted with permission from ref. . Copyright: 2022, Elsevier.

Figure 4

a) Chemical structure of the composite HACC/PVA coatings. b) The dual function of the coating for food packaging. Reprinted with permission from ref. . Copyright: 2020, Elsevier.

Figure 5

The stimulation index of lymphocyte proliferation in immunized chickens. Eight groups of chickens were immunized with (left to right) PBS, NDV‐loaded chitosan nanoparticle (CS−N), blank chitosan nanoparticle (CS−B), NDV‐loaded hydroxypropyltrimethyl ammonium chloride chitosan/chitosan nanoparticle (HACC−N), blank hydroxypropyltrimethyl ammonium chloride chitosan/chitosan nanoparticle (HACC−B), NDV‐loaded sulfated chitosan nanoparticle (SCS−N), blank sulfated chitosan nanoparticle (SCS−B), and commercial inactivated oil emulsion ND vaccine (Oil). Bars at the same week with the same superscript means no significant difference (P<0.05). Reprinted with permission from ref. . Copyright: 2020, Elsevier.

Scheme 12

Schematic illustration of reversible CO₂ capture by humidity swing. Reprinted with permission from ref. . Copyright: 2018, American Chemical Society.

Scheme 13

Schematic representation of A) the one‐pot and LbL deposition of PA66 fabrics and B) the mechanism of reaction. Reprinted with permission from ref. . Copyright: 2020, Elsevier.

Figure 6

SEM images of cells on the surface of Ch−X (control) and Chp‐X scaffolds prepared in the presence or not of the additives Silpuran® 2130 A/B (S) and Kolliphor® P188 (K) after 1 or 7 days of ADSC culture. White arrows or circles indicate spread cells on the material's surface. Scale bars: 50 μm. Reprinted with permission from ref. . Copyright: 2020, Elsevier.

Scheme 14

The effect of OPPC micelles in improving the oral absorption of PTX. A) The structure of OPPC and the strategy for constructing the PTX‐loaded OPPC micelles. B) The hypothetical mechanism of improved oral absorption of PTX by OPPC micelles. Reprinted with permission from ref. . Copyright: 2019, Elsevier.

Scheme 15

Schematic representation of nanogel components, swelling/shrinking cycle, and proposed mode of action for encapsulated DOX. Reprinted with permission from ref. . Copyright: 2016, American Chemical Society.

Figure 7

a) DPPH radical scavenging activity [%] and b) IC₅₀ of L, M, H, L–CMCH, M–CMCH and H‐CMCH. Different letters (a–d) indicate a significant difference between treatments (p≤0.05). Reprinted with permission from ref. . Copyright: 2020, MDPI.

Scheme 16

Schematic representation of PCL/CMCS/SA emulsion formation, microfiber generation using electrospinning, and osteoblast adhesion. Reprinted with permission from ref. . Copyright: 2020, Elsevier.

Scheme 17

Illustration of the fabrication and possible in‐vivo process and penetration behavior of DS−CD_C−HP‐Gel. The penetration behavior might be induced by transcellular and paracellular routes. Reprinted with permission from ref. . Copyright: 2021, MDPI.