Concepts for Developing Physical Gels of Chitosan and of Chitosan Derivatives

Abstract

Chitosan macro- and micro/nano-gels have gained increasing attention in recent years, especially in the biomedical field, given the well-documented low toxicity, degradability, and non-immunogenicity of this unique biopolymer. In this review we aim at recapitulating the recent gelling concepts for developing chitosan-based physical gels. Specifically, we describe how nowadays it is relatively simple to prepare networks endowed with different sizes and shapes simply by exploiting physical interactions, namely (i) hydrophobic effects and hydrogen bonds-mostly governed by chitosan chemical composition-and (ii) electrostatic interactions, mainly ensured by physical/chemical chitosan features, such as the degree of acetylation and molecular weight, and external parameters, such as pH and ionic strength. Particular emphasis is dedicated to potential applications of this set of materials, especially in tissue engineering and drug delivery sectors. Lastly, we report on chitosan derivatives and their ability to form gels. Additionally, we discuss the recent findings on a lactose-modified chitosan named Chitlac, which has proved to form attractive gels both at the macro- and at the nano-scale.

Keywords: Chitlac; chitosan; chitosan-derivatives; drug delivery; gel; gelling mechanisms; physical interactions; tissue engineering.

Figure 1

Schematic structure of chitosan: glucosamine (D) and N-acetyl-glucosamine (A) units.

Figure 2

Experimental setup for the gelation of chitosan solutions by using gaseous ammonia atmosphere. Adapted with permission from [31], Copyright 2005 American Chemical Society.

Figure 3

Experimental setup for developing chitosan-tripolyphosphate (TPP) macroscopic gels via external gelation. Adapted with permission from [42], Copyright 2014 American Chemical Society.

Figure 4

Gelling concept for synthetizing alginate-chitosan oligomers (left) and chitosan-alginate oligomers (right) gels via controlled internal gelation. Adapted with permission from [14], Copyright 2013 American Chemical Society.

Figure 5

Formation of chitosan-tripolyphosphate (TPP) microgels via salt-assisted mechanisms. The final micro-gel is formed by a controlled aggregation of primary nanoparticles into larger coacervates. Adapted with permission from [23], Copyright 2012 American Chemical Society.

Figure 6

Gelling mechanism of chitosan polyol-phosphates solutions. Adapted with permission from [101], Copyright 2013 American Chemical Society.

Figure 7

Classification of interpenetrating networks. SIPN: semi-interpenetrating networks (upper row); FIPN: full interpenetrating networks (lower row). In situ and sequential syntheses refer to the number of steps requiring for gel setting up.

Scheme 1

Synthesis of chitlac (CTL) through N-alkylation of chitosan in the presence of lactose.