Molecular dynamics simulations can predict the optimum drug loading amount in pectin hydrogels for controlled release

Banu Kocaaga, F. Seniha Guner*, Ozge Kurkcuoglu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


Determining an optimum drug concentration to modulate drug release from a flexible and dynamic system, such as hydrogels requires an extensive amount of experiments consuming time and money. Here, we conduct molecular dynamics (MD) simulations to predict an optimum drug concentration to load on low-methoxyl pectin hydrogels, which can maintain the structural integrity and achieve controlled drug release. Systems of low-methoxyl pectin hydrogel modeled as poly-galacturonic acid (PGAL) oligomers cross-linked with Ca2+ and procaine at different concentrations (0, 6, 30, 60, 90, 180 mg procaine/g hydrogel) are investigated. First, a series of 200 ns long all-atom MD simulations in explicit water with replicas are conducted reaching a total simulation time of 3.6 µs. We then assess our predictions with procaine release experiments from low-methoxyl pectin hydrogels, and calculation of storage G' and loss G'' moduli of hydrogel samples. Local and global motions of cross-linked PGAL oligomers from simulation trajectories are analyzed in detail to predict an optimum procaine concentration of 30 mg/g hydrogel. At this loading amount, polymer fluctuations are stabilized and initial monomer neighbors are maintained with a low average distance deviation of 1.5 Å so as to yield an intact hydrogel network. Results from MD simulations and experiments strongly agree. Pectin hydrogels loaded with 30 mg procaine /g have a low hydrogel degradation rate 0.001 g/min and a controlled in vitro drug release when compared to other samples, releasing all 30 mg of loaded procaine from 670 mg hydrogel in 24 h. Results indicate that drug release from the flexible host is mainly controlled by local and global motions of the polymer chains and non-bonded interactions between the system components. The computational approach taken here can be highly useful for similar polymer-based drug delivery systems.

Original languageEnglish
Article number103268
JournalMaterials Today Communications
Publication statusPublished - Jun 2022

Bibliographical note

Publisher Copyright:
© 2022 Elsevier Ltd


The authors thank the Istanbul Technical University Scientific Research Project Foundation (ITU BAP) [grant number 41165 ] for the partial support. Experimental part of this work was funded by The Scientific and Technological Research Council of Turkey (TUBITAK) [grant number 115M439 ]. The authors sincerely thank Herbstrith & Fox Company (Germany) for providing low-methylated pectin. The numerical calculations reported in this paper were partially performed at TUBITAK ULAKBIM, High Performance and Grid Computing Center (TRUBA resources) and the National Center for High Performance Computing of Turkey (UHeM) [grant number 1006812019 ].

FundersFunder number
ITU BAP41165
Istanbul Technical University Scientific Research Project Foundation
Türkiye Bilimsel ve Teknolojik Araştirma Kurumu


    • Controlled drug delivery
    • Molecular dynamics simulations
    • Polygalacturonic acid


    Dive into the research topics of 'Molecular dynamics simulations can predict the optimum drug loading amount in pectin hydrogels for controlled release'. Together they form a unique fingerprint.

    Cite this