Tailored Phytochitosomes as Targeted Nanotherapy for Alveolar Bone Regeneration in Diabetic Obese Rats

Background/Objectives: Individuals with diabetes often experience difficulties in the healing of their alveolar sockets. Furthermore, obesity is strongly associated with the development and progression of type 2 diabetes through complex metabolic and inflammatory mechanisms. The current study provides new insights into the use of Luteolin (LU) and/or chitosan vesicles (CHV) to accelerate bone regeneration, highlighting a biologically and clinically relevant approach that leverages implants as a clinical solution. Methods: Sixty rats were randomly categorized into five groups: Group I (negative control); Group II (positive control), diabetic and obese rats; Group III (LU-treated), diabetic and obese rats with an extraction socket loaded with LU; Group IV (CHV-treated), diabetic and obese rats with an extraction socket loaded with CHV; and Group V (LU-CHV), diabetic and obese rats with an extraction socket loaded with LU-CHV. After 2 and 6 weeks, rats' mandibles underwent histological, histomorphometric, biochemical, and statistical analyses. Results: The results demonstrated significant differences among the experimental groups. The LU-CHV formulation showed superior therapeutic performance compared with free luteolin and the untreated control group. In vitro release studies revealed sustained, controlled release from LU-CHV, whereas free luteolin exhibited rapid drug release. Additionally, LU-CHV significantly enhanced biological activity, as evidenced by improved anti-inflammatory and/or therapeutic markers compared to the other groups. These findings indicate that encapsulation within chitosan vesicles improved drug stability, bioavailability, and overall therapeutic efficiency. Conclusions: LU-CHV demonstrated superior efficacy compared to free luteolin, highlighting the advantage of chitosan-based vesicular delivery systems. LU-CHV not only enhanced controlled drug release and therapeutic outcomes but also presents a promising platform that could significantly advance targeted drug delivery strategies in inflammatory and metabolic disorders. The findings suggest that LU-CHV represents a transformative approach in improving treatment effectiveness and patient outcomes.