Formulation of stimuli-responsive gels containing silver complex with nicotinamide

The use of stimuli-responsive gels is increasingly widespread and includes almost all routes of administration. Their main property is the phase transition from sol to gel under the influence of physiological stimuli such as temperature, pH, ion presence, or enzymes. The aim of this formulation study was to prepare oral in situ gel containing silver complex with nicotinamide. We prepared formulations based on the thermosensitive polymer Pluronic^® F-127 (15% w/w), methylcellulose (0.25% w/w), and various concentrations of the ion-sensitive polymer sodium alginate (0.2%–4% w/w). Various properties were evaluated, such as pH, injectability, critical sol–gel transition temperature of sols, gelation capacity, as well as dissolution profile and antimicrobial activity. We found that sodium alginate affects the critical sol–gel transition temperature of sols, and with higher concentrations, the sol–gel transition temperature decreases. At a 4% w/w sodium alginate concentration, the presence of calcium cations was necessary for gel formation. Sodium alginate also significantly influenced the viscosity of sols; higher concentrations led to more viscous sols. The most suitable formulation contained 4% sodium alginate and was used to incorporate silver complex with nicotinamide, a new potential antimicrobial agent. The drug release kinetics most closely correlated with the first-order kinetics, and the drug was released via Fickian diffusion. During antimicrobial activity testing, the formulation demonstrated higher efficacy against Pseudomonas aeruginosa compared to a commercial dental gel containing chlorhexidine gluconate, although this difference was not statistically significant. Overall, the chlorhexidine gel showed greater efficacy against most of the tested bacteria, while the antimicrobial in situ gel maintained a consistent moderate level of antimicrobial activity.