Evaluation of 15d-PGJ2-loaded nanocapsules in periodontitis mouse model

Objectives: Peroxisome proliferator-activated γ and its natural agonist 15d-prostaglandin J₂ (15d-PGJ₂) has demonstrated excellent anti-inflammatory results in a different set of experimental models. Nowadays, it has been employed the polymeric nanostructures system to release drugs, which has the ability to change the therapeutic properties of the drug leading to several advantages such as increase in stability, slow and prolonged release, decreased toxicity and tissue-specific target. Thus, the present study had the objective to develop a nanotechonologic formulation as a drug carrier for 15d-PGJ₂ as well as to investigate the immunomodulatory effects of this formulation on periodontitis mouse model. 

Methods: Poly(D,L-lactide-co-glycolide) nanocapsules were used to encapsulate 15d-PGJ₂, and function as a drug carrier system. Balb/c mice were infected on day 0, 2 and 4 with Aggregatibacter actinomycetecomitans in methylcellulose (2%), and the groups of animals (n=6) were daily treated (15 days) with 1, 3 or 10 µg/kg of 15d-PGJ₂-NC (subcutaneously). Control groups were infected but did not receive the drug and another group was not infected. After 15 days, the animals were sacrificed and the submandibular lymph nodes were removed for FACS analysis and the jaws were analyzed for bone resorption. The gingival tissue was used for western blotting and ELISA. Statistical analyses were performed by Bonferroni test. 

Results: The infected animals treated with the 15d-PGJ₂-NC presented lower bone resorption (dose dependent, p<0.05) in comparison to the animals infected without treatment. Besides, infected-animals treated with 10 µg/kg of 15d-PGJ₂-NC had a statistical reduction of CD4+CD25+FOXP3+ cells and CD4/CD8 ratio in the submandibular lymph node (only at 10 µg/kg). Also, CD55 was up-regulated and ICAM-1 was down-regulated in the gingival tissue in the 10 µg/kg-treated group (p<0.05). Elevated amounts of 15d-PGJ₂ were found in the gingivae. 

Conclusions: The 15d-PGJ₂-NC has immunomodulatory effects decreasing the bone resorption and the inflammatory response in periodontitis.