Objective: Periodontitis is an oral disease categorized by disturbance of periodontal tissue and
the creation of periodontal pockets. Thymol (TH) loaded microsponge in situ gelling systems was formulated
for local action in the periodontal cavity for the management of periodontitis.
Methods: Solvent evaporation technique was utilized for the preparation of microsponges. A Fractional
Factorial Design (FFD) was used to screen the high risk variables impacting the characteristics of the
(TH) microsponges and further optimized using Box-Behnken design. The optimized microsponges were
then characterized by DSC, SEM, antimicrobial activity, in-vitro release, and then incorporated in the in situ gelling system. A ligature model was used to induce periodontitis in Sprague Dawley rats.
Results: The microsponges showed good characteristics, such as particle size, entrapment efficiency,
and mucoadhesiveness of 45 μm, 92.99 ± 0.2%, 96 ± 0.26%, respectively. SEM revealed the spherical
morphology of the microsponges with sustained release of TH for 10h and antimicrobial activity against
S. mutans and C. albicans. Treatment with Thymol Loaded in situ Gel (THLMG) showed a decrease in
gingival inflammation and tooth mobility as well as in serum biochemical parameters like serum Creactive
proteins, leucocyte count, alkaline phosphatase, and tartrate-resistant acid phosphatase, when
compared to disease group. The histopathological study of the periodontium confirmed a significant
reduction of inflammation and alveolar bone destruction (p<0.05) in rats.
Conclusion: THLMG decreased the infiltration of inflammatory cells and prevented osteoclastogenesis
and osteoblast apoptosis, which further favored a decrease in inflammation and alveolar bone loss in
periodontitis. Thus, THLMG could be a better alternative to synthetic antimicrobials and antibiotics to