Design and in vitro/ in vivo evaluations of a multiple-drug-containing gingiva disc for periodontotherapy

Abstract

In the current work, we set out to develop and evaluate a gingiva disc of cellulose acetate phthalate and poloxamer F-127 for the simultaneous delivery of multiple drugs, namely minocycline, celecoxib, doxycycline hyclate, and simvastatin, to abolish infection, impede inflammation, avert collagen destruction, and promote alveolar bone regeneration, respectively. In vitro release studies revealed the sustained release profiles of the drugs for 12 h and that they were active against Staphylococcus aureus, Escherichia coli and Streptococcus mutans. The in vivo bioactivity levels of these drugs were assessed by comparing the number of colony forming units during different phases of a study on Wistar rats, and the results showed a reduction in the number of bacterial colonies with the applied formulation. A mucosal irritation study conducted on Wistar rat gingiva confirmed the non-irritancy of the optimal gingiva disc. Hence, this customized, non-invasive polymeric gingiva disc displaying a sustained release of drugs can be a useful tool to treat acute to moderate stages of periodontitis.

Fig. 1. A schematic presentation of the design and development of the gingiva disc (a). A pictorial presentation of the developed gingiva disc (b).

Fig. 2. 3D-Response surface plots. As the amounts of polymer and poloxamer were increased, the tensile strength increased (a). As the amounts of polymer and poloxamer were increased, the amount of drug released first decreased and then increased (b).

Fig. 3. Drug release and permeation plots. Maximum percentages of drug released (minocycline) from all nine formulations, with F06 showing the highest maximum percentage of minocycline released (a). Cumulative percentage permeations of minocycline, celecoxib, doxycycline hyclate and simvastatin from the F06 formulation (b).

Fig. 4. A scanning electron microscopy (SEM) image of an uncoated disc, showing a smooth surface (a), and of the disc coated with hydroxyl-ethyl cellulose and showing a rough surface (b).

Fig. 5. A bar graph showing the comparisons of colony forming units (CFU) in rat's mouth at different phases of study. Before periodontitis induction, the CFU's in the rat's mouth were much lesser than the CFU's after periodontitis induction, whereas after the disease treatment with formulation the CFU count decreases significantly.

Fig. 6. Images of gingival areas in the mouths of control (a) and treated (b) rats. The gingival cells were observed to be quite similar in the two, suggesting that the formulation did not irritate the gingival tissue.