Rheological Study of Chitosan/Polyol-phosphate Systems: Influence of the Polyol Part on the Thermo-Induced Gelation Mechanism

Abstract

Thermo-sensitive gelling systems, like chitosan/polyol-phosphate, are candidates with a high potential for the design of biodegradable drug delivery systems, notably for in situ forming depots. They consist of stable and low viscosity aqueous solutions, liquid at room temperature, which turn into a gel state upon an increase of temperature (e.g., after subcutaneous administration). This technology enables a sustained release of potentially encapsulated active substances. Despite these thermo-gelling solutions being widely studied for the development of parenteral drug delivery systems, most commonly using β-glycerophosphate (β-GP) as gelling agent, the mechanism inducing the gelation and the role of the polyol part in this mechanism has not been clearly elucidated. To investigate the mechanism of the gelation process, comprehensive rheological studies were performed, comparing different chitosan/polyol-phosphate systems varying in the chemical structure of the polyol parts of the gelling agents. As reference, β-GP was compared to glucose-1-phosphate (G1-P) and glucose-6-phosphate (G6-P) and to a polyol-free phosphate salt, Na2HPO4, as well. Frequency sweep experiments at different temperatures or different gelling agent concentrations, temperature, and time sweep tests were performed as complementary experimental approaches. The results disclosed significant trends with widespread implications, establishing a relationship between the chemical structure of the polyol part and the macroscopic gelling behavior of the solutions, that is, transition temperature, gelation time, and gel strength. The new results presented in this study show that increasing the size of the polyol part prevents the interactions between the chitosan chains, strongly influencing the gelling process.

Chitosan-Based Thermosensitive Materials

“…On the other hand, the polyol unit is responsible for the thermal sensitivity of the Cs solution. Both the chemical structure and size of the polyol moiety play a significant role in controlling the gelation process [10]. In Figure 1 this gelation mechanism is clearly depicted.…”

“…Moreover, an interesting research published by Supper et al [10] demonstrated the specific role of the polyol-phosphate molecules on the thermo-physical gelation process. On the one hand, the phosphate moiety neutralizes the charges along the Cs chains up to the physiological pH, keeping them in the solution state at room temperature.…”

“…This opposite effect opens the possibilities of tuning the gelling process of Cs-GP system [11]. Representation of the gelation mechanism of Cs/polyol-phosphate solutions according to Supper et al [10]. Reprinted with permission from Ref.…”

Thermal gelation or gel melting: (ethylene glycol)113‐(l‐alanine)12 and (ethylene glycol)113‐(l‐lactic acid)12

“…G 0 >G 00 indicates the gel state, whereas G 0 <G 00 indicates the sol state of the system. 22,23 The PEG-PLA aqueous system showed the opposite trend. The PEG-PLA formed a gel with a modulus of about 75 Pa at 10 C, which turned into a sol as the temperature increased.…”

Osteoblastic differentiation of stem cells from human exfoliated deciduous teeth induced by thermosensitive hydrogels with strontium phosphate

“…Chitosan (GS) is an amino-polysaccharide and a natural biodegradable cationic polymer that has recently attracted much interest in studies and clinical applications; chitosan exhibits excellent biocompatibility, biodegradability, anti-microbial activity, wound healing ability, low immunogenicity, low cost, cell growth promotion, and osteo-conduction properties [1][2][3]. Chitosan is soluble in acidic solution because of the electrostatic repulsion among the polymer chains.…”