Metformin Hydrochloride-Loaded PLGA Nanoparticle in Periodontal Disease Experimental Model Using Diabetic Rats

Abstract

Evidence shows that metformin is an antidiabetic drug, which can exert favorable anti-inflammatory effects and decreased bone loss. The development of nanoparticles for metformin might be useful for increased therapeutic efficacy. The aim of this study was to evaluate the effect of metformin hydrochloride-loaded Poly (d,l-Lactide-co-glycolide) (PLGA)/(MET-loaded PLGA) on a ligature-induced periodontitis model in diabetic rats. MET-loaded PLGA were characterized by mean diameter, particle size, polydispensity index, and entrapment efficiency. Maxillae were scanned using Microcomputed Tomography (µCT) and histopathological and immunohistochemical analysis. IL-1β and TNF-α levels were analyzed by ELISA immunoassay. Quantitative RT-PCR was used (AMPK, NF-κB p65, HMGB1, and TAK-1). The mean diameter of MET-loaded PLGA nanoparticles was in a range of 457.1 ± 48.9 nm (p < 0.05) with a polydispersity index of 0.285 (p < 0.05), Z potential of 8.16 ± 1.1 mV (p < 0.01), and entrapment efficiency (EE) of 66.7 ± 3.73. Treatment with MET-loaded PLGA 10 mg/kg showed low inflammatory cells, weak staining by RANKL, cathepsin K, OPG, and osteocalcin, and levels of IL-1β and TNF-α (p < 0.05), increased AMPK expression gene (p < 0.05) and decreased NF-κB p65, HMGB1, and TAK-1 (p < 0.05). It is concluded that MET-loaded PLGA decreased inflammation and bone loss in periodontitis in diabetic rats.

The Design of Poly(lactide-co-glycolide) Nanocarriers for Medical Applications

“…The specific delivery of anti-inflammatory agents to the target site could potentially increase their therapeutic concentration in the inflamed tissue with reduced side effects (Gendelman et al, 2015), and the use of PLGA is particularly suitable to this application because of its favorable biodegradability and non-immunogenicity (Lamprecht et al, 2001). Davoudi et al (2018) described a carrier within a carrier system using intestinal organoids to transport 5-ASA encapsulated PLGA nanoparticle to treat inflammatory bowel disease, and Perreira's research involved the development of a metformin loaded nanoformulation that showed efficacy against periodontal inflammation in diabetic rats (Pereira et al, 2018). Gholizadeh et al (2018) have formulated a dactolisib-PLGA nanoparticle that showed activity against inflamed endothelial cells and more recently, Yang (2019) group reported the synthesis of a crocetin-loaded nanoparticles that reduced the level of pro-inflammatory cytokines in renal tissue and therefore shows potential for the treatment of diabetes induced nephropathy.…”

High Mobility Group Box 1 Expression in Oral Inflammation and Regeneration

“…Metformin, the first-line medication for the treatment of type 2 diabetes, is also considered an HMGB1 inhibitor because it directly binds HMGB1 and inhibits the pro-inflammatory activity (63). Metformin and metformin hydrochloride-loaded poly lactic-co-glycolic acid nanoparticles decreased the inflammatory response and bone loss in a rat periodontitis model (64,65). These findings indicate that metformin does not only have a hypoglycemic action but also has an anti-inflammatory effect to block HMGB1, and it might be effective in diabetes-associated periodontitis.…”

Emerging Nanotechnology in Non-Surgical Periodontal Therapy in Animal Models: A Systematic Review

“…After full reading, 10 articles were excluded (Supplemental Table S2). Finally, 11 studies were included: 2 with antibacterial agents [26,27], 8 with anti-inflammatory agents [28][29][30][31][32][33][34][35] and 1 with both [36]. The process of article selection is summarized in Figure 1.…”

“…The follow-up of the studies was up to 28 days. Two studies used mice [27,28] and 9 used rats [26,[29][30][31][32][33][34][35][36] (including one with systemically compromised animals with diabetes mellitus [32]). Number of animals ranged between 4 and 20 per group.…”