Formulation and optimization of a new cationic lipid-modified PLGA nanoparticle as delivery system for Mycobacterium tuberculosis HspX/EsxS fusion protein: An experimental design

Document Type: Research article

Authors

1 Department of Microbiology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.

2 Antimicrobial Resistance Research Center, Department of Medical Bacteriology and Virology, Qaem University Hospital, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

3 Targeted Drug Delivery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

4 Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

5 Nanotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Abstract

Polymeric particles and liposomes are efficient tools to overcome the low immunogenicity of subunit vaccines. The aim of the present study was formulation and optimization of a new cationic lipid-modified PLGA nanoparticles (NPs) as a delivery system for Mycobacterium tuberculosis HspX/EsxS fusion protein. The cationic lipid-modified PLGA NPs containing HspX/EsxS fusion protein were prepared using a modified double emulsion solvent evaporation method. Scanning electron microscopy and dynamic light scattering (DLS) tools were used to determine physical properties of hybrid NPs. A multi-level full factorial design was used to evaluate the influence of two factors of PLGA:DDA ratio (w/w) and PVA concentration (%) on size, surface charge, polydispersity index, encapsulation efficiency and yield. Finally, the optimal formulation was achieved based on desired responses. Mathematical models were obtained to indicate the relation between the studied factors and responses. The DDA concentration showed an increasing effect on surface charge and also a decreasing effect on particle size, encapsulation efficiency and yield. Higher amounts of DDA, increased surface charge of NPs, however, the size, encapsulation efficiency and yield were decreased. The influence of various concentrations of PVA on different physical characteristics of PLGA:DDA hybrid NPs was variable. The optimal formulation was consisted of 0.91 (55:5, w/w) ratio of PLGA:DDA and 0.5% PVA. The hybrid NPs showed acceptable particle size distribution, strong positive surface charge, prolonged antigen release and good encapsulation efficiency in comparison to PLGA alone. However, further preclinical and clinical studies are needed.

Keywords

Main Subjects