Novel 20% doxycycline-loaded PLGA nanospheres as adjunctive therapy in chronic periodontitis in type-2 diabetics: randomized clinical, immune and microbiological trial

Objective This study evaluated the clinical, microbiological, and immunological results of poly lactic-co-glycolic acid (PLGA) nanospheres containing 20% doxycycline (DOXY) in the treatment of type-2 diabetic patients (DM-2) with chronic periodontitis (CP). Material and methods A parallel, double-blind, randomized, placebo-controlled clinical trial was conducted in DM-2 presenting severe and generalized CP. All patients received one-stage full-mouth ultrasonic debridement (FMUD) and they were randomly divided into two groups: PLAC ( n = 20)—local application of placebo PLGA nanospheres, and DOXY ( n = 20)—local application of doxycycline-loaded nanospheres; both in six non-contiguous sites. Clinical, metabolic (fasting plasma glucose level—FPG and glycated hemoglobin—HbA1c), cytokine pattern (multiplexed bead immunoassay) and microbiological assessments were performed at baseline, and 1, 3, and 6 months after treatment. Results Both groups showed clinical improvement in all parameters after treatment ( p < 0.05). Deep pockets showed improvements in bleeding on probing—BoP (3 and 6 months), PD (at 3 months), and CAL gain (at 1 and 3 months) favoring DOXY ( p < 0.05). The percentage of sites presenting PD reduction and CAL gain ≥ 2 mm was higher in DOXY at 3 months ( p < 0.05). DOXY group exhibited a significant increase in the levels of anti-inflammatory interleukin (IL)-10 and a reduction in IL-8, IFN-y, IL-6, and IL-17 ( p < 0.05), significant reduction in periodontal pathogens ( p < 0.05), and a lower mean percentage of HbA1C at 3 months ( p < 0.05). Conclusion DOXY nanospheres may be considered a potential adjunct to mechanical debridement in the therapy of periodontitis in DM-2, offering additional benefits in deep pockets, improving the cytokine profile, and reducing periodontal pathogen levels. Clinical relevance The use of locally applied doxycycline nanospheres may represent an adjunctive therapeutic approach in the treatment of periodontal disease in type-2 diabetic patients, achieving additional benefits in the local modulation of cytokines, microbial reduction, and clinical parameters, especially in deep pockets.