Damghan University Journal of Nano Simulation 3092-7722 1 1 2025 06 01 Investigating variability in PLGA monomers: A comparative study of electronic properties and their role in drug delivery systems 1 8 492 10.22128/jons.2025.964.1001 EN Laleh Khorshidi Department of Physical Chemistry, Faculty of Chemistry, University of Mazandaran, Babolsar, Iran 0000-0002-7126-4551 Davood Farmanzadeh Department of Physical Chemistry, Faculty of Chemistry, University of Mazandaran, Babolsar, Iran Sima Esmailpour Faculty of Chemistry, Shahrood University of Technology, Shahrood, Iran Journal Article 2025 02 20 PLGA (poly(lactic-co-glycolic) acid) is a biodegradable copolymer commonly used in drug delivery. It is composed of monomers X and Y, which influence its physical and chemical properties. Incorporating hydrophilic polymers like polyethylene glycol (PEG) into PLGA enhances the circulation half-life of nanoparticles. This study employs computational methods to investigate how variations in the number and arrangement of monomers X and Y, as well as PEG integration, affect PLGA’s properties. Using Density Functional Theory (DFT) calculations, we analyze several physicochemical characteristics, including the energy gap and dipole moment. Our results show that PEG incorporation reduces the energy gap, with configurations like XYXX-PEG-XYXX and XXYYY emerging as promising drug carrier candidates. Furthermore, an increased ratio of X to Y generally elevates the dipole moment, particularly with PEG present, which improves the dipole moment further. Noncovalent interaction analysis indicates that certain PLGA monomers may exhibit beneficial van der Waals interactions, enhancing the sustained release of therapeutic agents. https://jons.du.ac.ir/article_492_147f6ab3c025d12aae7b8184210a9328.pdf