Pioglitazone-Loaded PLGA Nanoparticles: Towards the Most Reliable Synthesis Method.

Biagio Todaro,Stefano Luin,Aldo Moscardini

doi:10.3390/ijms23052522

Abstract

Recent findings have proved the benefits of Pioglitazone (PGZ) against atherosclerosis and type 2 diabetes. Since the systematic and controllable release of this drug is of significant importance, encapsulation of this drug in nanoparticles (NPs) can minimize uncontrolled issues. In this context, drug delivery approaches based on several poly(lactic-co-glycolic acid) (PLGA) nanoparticles have been rising in popularity due to their promising capabilities. However, a fully reliable and reproducible synthetic methodology is still lacking. In this work, we present a rational optimization of the most critical formulation parameters for the production of PGZ-loaded PLGA NPs by the single emulsification-solvent evaporation or nanoprecipitation methods. We examined the influence of several variables (e.g., component concentrations, phases ratio, injection flux rate) on the synthesis of the PGZ-NPs. In addition, a comparison of these synthetic methodologies in terms of nanoparticle size, polydispersity index (PDI), zeta potential (ζp), drug loading (DL%), entrapment efficiency (EE%), and stability is offered. According to the higher entrapment efficiency content, enhanced storage time and suitable particle size, the nanoprecipitation approach appears to be the simplest, most rapid and most reliable synthetic pathway for these drug nanocarriers, and we demonstrated a very slow drug release in PBS for the best formulation obtained by this synthesis.

Highlights

Received: 28 January 2022Atherosclerosis is a heavy condition characterized by progressive inflammation and slowly calcifying lesions in the intima and inner media of the arterial wall due to plaque formation [1]
Several nanoparticle platforms to encapsulate PGZ were developed via single emulsification-solvent evaporation or nanoprecipitation approaches
Using the lower-weight poly(lactic-co-glycolic acid) (PLGA) in single emulsification-solvent evaporation method, polymer strands precipitated within the solution, meaning that NPs were not obtained

Summary

Introduction

Atherosclerosis is a heavy condition characterized by progressive inflammation and slowly calcifying lesions in the intima and inner media of the arterial wall due to plaque formation [1]. The incidence of this disease is rising worldwide. PGZ is a slightly hydrophobic small molecule (logP = 2.3; experimental value from Human Metabolome Database) commonly used in treatment, or progression control, of type 2 diabetes This drug acts by principally stimulating the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ), increasing, the sensitivity of peripheral tissues to insulin, reducing gluconeogenesis resistance in the liver and inhibiting macrophage activation

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