Chitosan Nanoparticles Prepared by Ionotropic Gelation: An Overview of Recent Advances

Abstract

The objective of this review is to summarize recent advances in chitosan nanoparticles prepared by ionotropic gelation. Significant progress has occurred in this area since the method was first reported. The gelation technique has been improved through a number of creative methodological modifications. Ionotropic gelation via electrospraying and spinning disc processing produces nanoparticles with a more uniform size distribution. Large-scale manufacturing of the nanoparticles can be achieved with the latter approach. Hydrophobic and hydrophilic drugs can be simultaneously encapsulated with high efficiency by emulsification followed by ionic gelation. The turbulent mixing approach facilitates nanoparticle formation at a relatively high polymer concentration (5 mg/mL). The technique can be easily tuned to achieve the desired polymer/surface modifications (e.g., blending, coating, and surface conjugation). Using factorial-design-based approaches, optimal conditions for nanoparticle formation can be determined with a minimum number of experiments. New insights have been gained into the mechanism of chitosan-tripolyphosphate nanoparticle formation. Chitosan nanoparticles prepared by ionotropic gelation tend to aggregate/agglomerate in unfavorable environments. Factors influencing this phenomenon and strategies that can be adopted to minimize the instability are discussed. Ionically cross-linked nanoparticles based on native chitosan and modified chitosan have shown excellent efficacy for controlled and targeted drug-delivery applications.

Therapeutic effect of low molecular weight chitosan containing sepia ink on ethanol-induced gastric ulcer in rats

“…Collagen expression is often used to evaluate the healing rate of wounds. Collagen is mainly secreted by fibroblasts, which is critical for ulcer healing 20 . Hydroxyproline (Hyp), as a characteristic amino acid of collagen, are often used as an indicator for detecting the collagen content 21 .…”

The different ways to chitosan/hyaluronic acid nanoparticles: templated vs direct complexation. Influence of particle preparation on morphology, cell uptake and silencing efficiency

“…Biodegradation can occur both enzymatically and oxidatively [4]. A number of methods can be employed to prepare chitosan-based nanoparticles [5][6][7][8], the most popular being ionotropic gelation and polyelectrolyte complexation. The distinction between the two is subtle, since they are based on a common driving force, i.e., the electrostatic attraction between protonated amines on chitosan and multiply charged anions, which effectively act as cross-linkers.…”

Chitosan-Based Biomimetically Mineralized Composite Materials in Human Hard Tissue Repair

“…There are two mechanisms of this technique: physically crosslinked hydrogels are formed by intermolecular interaction (electrostatic interaction, hydrogen bonding interaction, and hydrophobic interaction), with small anionic molecules, polyanions, or hydrophobic polymers; and chemical crosslinked hydrogels are formed by the covalent linking of chitosan and other polymers or small cross-linkers through the reaction of their functional groups, where the bond formation is irreversible [ 66 , 67 ]. Belonging to physical crosslinking, ionotropic gelation is one of the most widespread techniques for the preparation of chitosan nanoparticles, which is based on the electrostatic interaction between the amine group of chitosan and a negatively charged group of polyanions, such as tripolyphosphate [ 68 , 69 , 70 ]. In this method, chitosan is firstly dissolved in acetic acid, then polyanion is added, and nanoparticles are formed spontaneously under mechanical stirring at room temperature [ 71 ].…”