Highlights

  • Ionic gelation is the preferred technique to produce chitosan nanoparticles.
  • The properties of chitosan nanoparticles can be controlled by tuning the mixing technique of cross-linker and chitosan solution, concentration of chitosan, and adding salts with varying valency.
  • Drop-wise mixing of cross-linker into chitosan solution produces more stable nanoparticles than single-shot mixing.
  • Increases in salt concentration in chitosan solution provide larger nanoparticle size.
Introduction

Chitosan (CS) is one of the abundant polysaccharides that can be derived from abundant natural sources such as plants, arthropods, etc. Producing chitosan nanoparticles (CSNPs) with an ionic gelation process has attracted the interest of researchers in recent years due to their distinctive properties. However, tuning CSNPs for specific functional properties can be challenging. But the ionic gelation process can be manipulated by adjusting several parameters, including the;

  • Mixing technique of cross-linker
  • Chitosan solution
  • pH
  • Chitosan concentration chitosan
  • Addition of salts with varying valency
  • Temperature
Chemistry of Ionic Gelation

Ionic gelation is the most common method used in Chitosan Nanoparticles (CSNPs) production, because of its ease and low cost. In ionic gelation method, the CSNPs are made by the formation of the positively charged amino groups in the chitosan molecule, and the negatively charged groups of polyanion or crosslinker. For example, Chitosan/Gum particles with narrow size distributions can be prepared by slowing down the ionotropic gelation by adding NaCl to the parent chitosan solutions. This slower gelation allowed the Gum to mix into the chitosan to result in a more uniformed homogenous solution which also may assist in increased stability.

Effect of Mixing Technique of Crosslinker

The sensitivity of the Chitosan/Gum particle properties depends on the mixing procedure used. Table 1 shows the zeta potential 37.2±5.07 mV results of adding Arabic Gum drop-by-drop. Whereas a single-shot results in a zeta potential of 32.6 ± 6.37 mV. Therefore, adding Arabic Gum drop-by-drop to chitosan solution produced more stable nanoparticles.

Table 1 - Single Shot Vs Drop-By-Drop Arabic Gum Mixing
Effect of Salt on Nanoparticles

Adding a high concentration of the monovalent salt (NaCl) enhances particle size by controlling the crosslinking between Chitosan (CS) and Arabic Gum (AG). It reduces agglomeration, and increases particle size, and surface area; all increasing the ability to tune the properties of the Chitosan Nanoparticles. The significant increase in particle size with the addition of a high concentration of salt had the following two effects on the CS/AG particle:

(1) screening of electrostatic repulsion between their aggregating subunits, which increases their collision frequency; and
(2) competitive binding of Cl- and gum anions, which weakens CS/Gum binding.

Due to this enhanced aggregation, higher NaCl concentrations produced larger particles.

Table 2 - Effect of Salt on Nanoparticles
Effect of Chitosan Concentration on Nanoparticle Properties

The particle size of Chitosan Nanoparticles was increased significantly increased from 42.67±8.89 nm to 91.33±4.19 nm when Chitosan concentration was increased from 1%(w/v) to 2% (w/v).

Larger particle size was produced with higher Chitosan concentration and vice versa. The larger particle size obtained was partly due to the increased viscosity of the Chitosan solution which had less solubility within the ionic gelation process.

Table 3: Effect of Chitosan Concentration on Nanoparticles Properties
We thank Md. Mehedi Anas for this (his) thesis paper submitted in partial fulfillment of the requirements for the award of Bachelor of Science in Biomedical Engineering. We also thank him for the review of this (his) thesis paper developed for ChitoLytic, Inc.
Reference Cited:
Tuning the Functional Properties of Chitosan Nanoparticles by Controlling Ionic Gelation for Biomedical Application, By Md. Mehedi Anas
Supervised By Dr. Muhammad Tarik Arafat (Professor, BME, BUET)
A thesis paper submitted in partial fulfillment of the requirements for the award of Bachelor of Science in Biomedical Engineering
Department of Biomedical Engineering
Bangladesh University of Engineering and Technology
Dhaka-1000, Bangladesh
May 2022