Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Oct 31;16(21):3065.
doi: 10.3390/polym16213065.

The Excellent Chemical Interaction Properties of Poloxamer and Pullulan with Alpha Mangostin on Amorphous Solid Dispersion System: Molecular Dynamics Simulation

Agus Rusdin  1   2 , Muchtaridi Muchtaridi  2 , Sandra Megantara  2 , Yoga Windhu Wardhana  1 , Taufik Muhammad Fakih  3 , Arif Budiman  1
Affiliations

The Excellent Chemical Interaction Properties of Poloxamer and Pullulan with Alpha Mangostin on Amorphous Solid Dispersion System: Molecular Dynamics Simulation

Agus Rusdin et al. Polymers (Basel). .

Abstract

Background: Alpha mangostin (AM) has demonstrated significant potential as an anticancer agent, owing to its potent bioactivity. However, its clinical application is limited by poor solubility, which hampers its bioavailability and effectiveness. Amorphous solid dispersion (ASD) presents a promising technique to enhance the solubility and stability of AM. Molecular dynamics simulation offers a rapid, efficient, and precise method to evaluate and optimize ASD formulations before production.

Aim of study: In this study, we conducted molecular dynamics simulations to explore the ASD development of AM with poloxamer and pullulan.

Result: Our results revealed that AM-poloxamer complexes exhibit superior interaction characteristics compared to AM-pullulan, with a 1:5 ratio of AM to poloxamer and a cooling rate of 1 °C/ns demonstrating the most favorable outcomes. This combination showed enhanced hydrogen bonding, a more compact molecular structure, and higher stability, making it the optimal choice for ASD formulation.

Conclusion: The integration of molecular dynamics simulation into ASD development significantly accelerates the formulation process and provides critical insights into achieving a stable and effective AM dispersion. The AM-poloxamer complex, particularly at a 1:5 ratio with a 1 °C/ns cooling rate, offers the best potential for improving AM solubility and therapeutic efficacy.

Keywords: alpha mangostin; amorphous solid dispersion; molecular dynamic; poloxamer; pullulan.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Illustrates the value of RMSD during molecular docking simulation between AM–poloxamer (a) and AM–pullulan (b). The x-axis represents cooling duration in nanoseconds, while the y-axis indicates the RMSD in Armstrong.
Figure 2
Figure 2
Illustrates the value of RMSF during molecular docking simulation between AM–poloxamer (a) and AM–pullulan (b). The x-axis represents atom/residue, while the y-axis indicates the RMSF in Armstrong.
Figure 3
Figure 3
Illustrates the quantity of hydrogen bonding interactions established between AM–poloxamer (a) and AM–pullulan (b). The x-axis represents time in nanoseconds, while the y-axis indicates the amount of H-Bond.
Figure 4
Figure 4
Illustrates the value of SASA during molecular docking simulation between AM–poloxamer (a) and AM–pullulan (b). The x-axis represents time in picoseconds, while the y-axis indicates the SASA in nm2.
Figure 5
Figure 5
Illustrates the value of RDF value during molecular docking simulation between AM–poloxamer (a) and AM–pullulan (b). The x-axis (horizontal) represents the distance between atoms/molecules (in nanometers), and the y-axis (vertical) represents the probability of finding them at those distances.
Figure 6
Figure 6
Illustrates the value of the gyration radius during molecular docking simulation between AM–poloxamer (a) and AM–pullulan (b). The x-axis represents time in nanoseconds, while the y-axis indicates the gyration radius in nm.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Sari N., Katanasaka Y., Sugiyama Y., Miyazaki Y., Sunagawa Y., Funamoto M., Shimizu K., Shimizu S., Hasegawa K., Morimoto T. Alpha Mangostin Derived from Garcinia Magostana Linn Ameliorates Cardiomyocyte Hypertrophy and Fibroblast Phenotypes in Vitro. Biol. Pharm. Bull. 2021;44:1465–1472. doi: 10.1248/bpb.b21-00294. - DOI - PubMed
    1. Nalla L.V., Dharavath A., Behera S.K., Khairnar A. Alpha Mangostin Inhibits Proliferation, Migration, and Invasion of Human Breast Cancer Cells via STAT3 Inhibition. Adv. Cancer Biol. Metastasis. 2023;7:100089. doi: 10.1016/j.adcanc.2023.100089. - DOI
    1. Chen C.M., Hsieh S.C., Lin C.L., Lin Y.S., Tsai J.P., Hsieh Y.H. Alpha-Mangostin Suppresses the Metastasis of Human Renal Carcinoma Cells by Targeting MEK/ERK Expression and MMP-9 Transcription Activity. Cell. Physiol. Biochem. 2017;44:1460–1470. doi: 10.1159/000485582. - DOI - PubMed
    1. Nauman M.C., Won J.H., Petiwala S.M., Vemu B., Lee H., Sverdlov M., Johnson J.J. α-Mangostin Promotes In Vitro and In Vivo Degradation of Androgen Receptor and AR-V7 Splice Variant in Prostate Cancer Cells. Cancers. 2023;15:2118. doi: 10.3390/cancers15072118. - DOI - PMC - PubMed
    1. Díaz L., Bernadez-Vallejo S.V., Vargas-Castro R., Avila E., Gómez-Ceja K.A., García-Becerra R., Segovia-Mendoza M., Prado-Garcia H., Lara-Sotelo G., Camacho J., et al. The Phytochemical α-Mangostin Inhibits Cervical Cancer Cell Proliferation and Tumor Growth by Downregulating E6/E7-HPV Oncogenes and KCNH1 Gene Expression. Int. J. Mol. Sci. 2023;24:3055. doi: 10.3390/ijms24033055. - DOI - PMC - PubMed

LinkOut - more resources