A yeast-malic acid crosslinker/polyacrylic acid hydrogel containing doxycycline for the treatment of periodontitis

Doxycycline (DX) is a drug of choice for the treatment of periodontitis, with the limitation of requiring a high dose, which may be overcome by the preparation of a targeted controlled-release hydrogel containing a newly synthesized yeast-malic acid crosslinker (YMC). YMC was synthesized via thermochemical modification of yeast with malic acid at 100-140 °C and compared with glutaraldehyde-saturated toluene (GST). Swelling capacity, acid and carboxyl content, scanning electron microscopy (SEM) imaging, Brunauer-Emmett-Teller (BET) analysis, viscosity, cross-linking density, DX loading and release behavior at pH 6.5, mucoadhesion, and antimicrobial and periodontal efficacy of the glutaraldehyde hydrogel (HGG) and YMC hydrogel (HGY) were compared. Changes from C-O (1421 cm) to C 00000000 00000000 00000000 00000000 11111111 00000000 11111111 00000000 00000000 00000000 OOR (1702 cm) in the infrared spectroscopy, along with changes in the degree of substitution from 0 to 0.39, degree of esterification from 0 to 40 ± 1.5 and COOH content from 129 ± 0.5 to 290 ± 0.5 (meq. per 100 g), were found between yeast to YMC, respectively. The results revealed 1.5 times more dynamic swelling, 0.25-fold decrease in acid content, 2.3-fold increase in carboxyl content, and 1.2- and 2.1-fold increases in cross-linking density and viscosity of HGY as compared to HGG, respectively. The SEM and BET results revealed that HGY had a 2 times greater porous surface than HGG. HGY/DX was 35 ± 2% more effective in controlling periodontitis bacteria, decreased periodontal depth from 4 to 3.2 mm, and gingival index from 3 to 1 as compared to HGG/DX in patients suffering from periodontitis. HGY/DX not only serves as a tool for the controlled release of DX in periodontal pockets but also contributes to the treatment of gingival periodontitis.