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

Aline Pereira,Maria Galvan,Adriana De Rezende,Gerly Brito,Caroline Medeiros,Gerlane Guerra,Maria Lima,Raul Bortolin,Arnóbio Silva Júnior,Emanuell Silva,Aurigena Araújo,Raimundo Araújo Júnior,Flávia Pirih

doi:10.3390/ijms19113488

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.

Highlights

Polymeric nanoparticles are particles with a diameter between 1 and 1000 nm [1]
Among the polymers studied for nanoparticle preparation, poly lactic-co-glycolic acid (PLGA) has been widely used because it is a biocompatible and biodegradable synthetic polymer that has been approved by the United States Food and Drug Administration (USFDA) [6]
It is important to consider that the animals in this study were not diabetic, since our objective was to verify the pleiotropic effect of metformin in inflammation and bone loss in a periodontal disease experimental model

Summary

Introduction

Polymeric nanoparticles are particles with a diameter between 1 and 1000 nm [1]. Nanoparticulate drug release systems using biodegradable polymers have been extensively studied for various applications [2,3]. Among the polymers studied for nanoparticle preparation, poly lactic-co-glycolic acid (PLGA) has been widely used because it is a biocompatible and biodegradable synthetic polymer that has been approved by the United States Food and Drug Administration (USFDA) [6]. Polymer composition is the most important factor to determine the hydrophilicity and degradation rate of a delivery matrix. The amount of glycolic acid is a critical parameter in tuning the hydrophilicity of the matrix and the degradation and drug release rate [7]

Objectives

Methods

Results