RESUMEN
Periodontitis and hypertension often occur as comorbidities, which need to be treated at the same time. To resolve this issue, a controlled-release composite hydrogel approach is proposed with dual antibacterial and anti-inflammatory activities as a resolution to achieve the goal of co-treatment of comorbidities. Specifically, chitosan (CS) with inherent antibacterial properties is cross-linked with antimicrobial peptide (AMP)-modified polyethylene glycol (PEG) to form a dual antibacterial hydrogel (CS-PA). Subsequently, curcumin loaded into biodegradable nanoparticles (CNP) are embedded in the hydrogel exhibiting high encapsulation efficiency and sustained release to achieve long-term anti-inflammatory activities. In a mouse model of periodontitis complicated with hypertension, CS-PA/CNP is applied to gingival sulcus and produced an optimal therapeutic effect on periodontitis and hypertension simultaneously. The therapeutic mechanisms are deeply studied and indicated that CS-PA/CNP exerted excellent immunoregulatory effects by suppressing the accumulation of lymphocytes and myeloid cells and enhanced the antioxidant capacity and thus the anti-inflammatory capacity of macrophages through the glutathione metabolism pathway. In conclusion, CS-PA/CNP has demonstrated its superior therapeutic effects and potential clinical translational value in the co-treatment of periodontitis and hypertension, and also serves as a drug delivery platform to provide combinatorial therapeutic options for periodontitis with complicated pathogenesis.