Ternary Solid Dispersion Improves Anti-cancer Activity of Alpha-mangostin Against MCF-7 Breast Cancer Cells
Abstract
BACKGROUND: Alpha-mangostin (AM) exhibits potent anti-breast cancer activity but its therapeutic effectiveness is constrained due to low aqueous solubility and poor bioavailability. Ternary solid dispersions (TSDs) were developed by adding another excipient to address these challenges. Nevertheless, limited studies have systematically evaluated whether improvements in dissolution and stability achieved through TSD systems are translated into enhanced in vitro cytotoxicity of AM. Therefore, TSD system of AM with Eudragit (EUD) and Poloxamer (POL) was developed, and in vitro cytotoxicity activity was evaluated as a preliminary proof-of-concept in MCF-7 breast cancer cells.
METHODS: TSD of AM was prepared by solvent evaporation and characterized by Power X-Ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC), and Fourier Transform Infrared (FT-IR) Spectroscopy. The pharmaceutical properties were evaluated by in vitro dissolution test using a standard paddle apparatus, while physical stability was assessed under two relative humidity environments. The in vitro anticancer efficacy was examined in MCF-7 breast cancer cell using an MTT assay.
RESULTS: Amorphization of TSD was confirmed by a halo pattern with PXRD measurements and the absence of an AM melting peak in the DSC curve. FT-IR analysis revealed hydrogen bond interactions between the carbonyl group of AM and EUD/POL protons. TSD system significantly improved the dissolution profile and enhanced cytotoxic effects, reducing cell viability to 1.17% at 16 µg/mL with an IC50 of 7.11 μg/mL (CI 95%: 6.626-7.591).
CONCLUSION: The TSD system significantly improved dissolution profile and in vitro cytotoxicity in MCF-7 breast cancer cells, providing proof-of-concept for enhancing the biological performance of AM.
KEYWORDS: alpha-mangostin, ternary solid dispersions, dissolution, MCF-7, cytotoxicity
Full Text:
PDFReferences
Zafar A, Khatoon S, Khan MJ, Abu J, Naeem A. Advancements and limitations in traditional anti-cancer therapies: a comprehensive review of surgery, chemotherapy, radiation therapy, and hormonal therapy. Discov Oncol. 2025; 16(1): 607, CrossRef.
Abdihalim TS, Idris AAA. Mucin level as a potential biomarker for breast cancer diagnosis. Mol Cell Biomed Sci. 2022; 6(3): 117-20, CrossRef.
Prayogo AA, Wijaya AY, Hendrata WM, Looi SS, I'tishom R, Hakim L, et al. Dedifferentiation of MCF-7 breast cancer continuous cell line, development of breast cancer stem cells (BCSCs) enriched culture and biomarker analysis. Indones Biomed J. 2020; 12(2): 115-23, CrossRef.
Xu Y, Gong M, Wang Y, Yang Y, Liu S, Zeng Q. Global trends and forecasts of breast cancer incidence and deaths. Sci Data. 2023; 10(1): 334, CrossRef.
Siegel Mph RL, Giaquinto AN, Ahmedin |, Dvm J, Siegel RL. Cancer statistics, 2024. CA Cancer J Clin. 2024; 74(1): 12-49, CrossRef.
Wu J, Fan D, Shao Z, Xu B, Ren G, Jiang Z, et al. CACA Guidelines for Holistic Integrative Management of Breast Cancer. Holist Integr Oncol. 2022; 1(1): 7, CrossRef.
Rahmawati DR, Murwanti R, Jenie RI, Nurrochmad A. Pentagamavunon-1 enhances the anticancer effects of doxorubicin on triple-negative breast cancer cells in monolayers and 3D cancer spheroid models. Indones Biomed J. 2025; 17(3): 241-51, CrossRef.
Kurose H, Shibata MA, Iinuma M, Otsuki Y. Alterations in cell cycle and induction of apoptotic cell death in breast cancer cells treated with α-mangostin extracted from mangosteen pericarp. Biomed Res Int. 2012; 2012(1): 672428, CrossRef.
Setiawati A. Anticancer activity of mangosteen pericarp dry extract against MCF-7 breast cancer cell line through estrogen receptor-Α. Indones J Pharm. 2014; 25(3): 119-24, CrossRef.
Kritsanawong S, Innajak S, Imoto M, Watanapokasin R. Antiproliferative and apoptosis induction of α-mangostin in T47D breast cancer cells. Int J Oncol. 2016; 48(5): 2155-65, CrossRef.
Ishizuka Y, Ueda K, Okada H, Takeda J, Karashima M, Yazawa K, et al. Effect of drug-polymer interactions through hypromellose acetate succinate substituents on the physical stability on solid dispersions studied by fourier-transform infrared and solid-state nuclear magnetic resonance. Mol Pharm. 2019; 16(6): 2785-94, CrossRef.
Que C, Qi Q, Zemlyanov DY, Mo H, Deac A, Zeller M, et al. Evidence for halogen bonding in amorphous solid dispersions. Cryst Growth Des. 2020; 20(5): 3224-35, CrossRef.
Atsukawa K, Amari S, Takiyama H. Solid dispersion melt crystallization (SDMC) concept using binary eutectic system for improvement of dissolution rate. J Ind Eng Chem. 2021; 101: 21-7, CrossRef.
Alatas F, Ratih H, Sutarna TH, Fauzi ML. The binary and ternary amorphous systems of candesartan cilexetil preparation to improve its solubility. Int J Appl Pharm. 2024; 16(5): 367-72, CrossRef.
Borde S, Paul SK, Chauhan H. Ternary solid dispersions: Classification and formulation considerations. Drug Dev Ind Pharm. 2021; 47(7): 1011-28, CrossRef.
Sohn JS, Kim EJ, Park JW, Choi JS. Piroxicam ternary solid dispersion system for improvement of dissolution (%) and in vitro anti-inflammation effects. Mater Sci Eng B. 2020; 261: 114651, CrossRef.
Saberi A, Kouhjani M, Yari D, Al. E. Development, recent advances, and updates in binary, ternary co-amorphous systems, and ternary solid dispersions. J Drug Deliv Sci Technol. 2023; 86: 104746, CrossRef.
Budiman A, Lailasari E, Nurani NV, Yunita EN, Anastasya G, Aulia RN, et al. Ternary solid dispersions: A review of the preparation, characterization, mechanism of drug release, and physical stability. Pharmaceutics. 2023; 15(8): 2116, CrossRef.
Amaliah S, Aulifa D, Gazzali A, Budiman A. Ternary solid dispersions as an alternative approach to enhance pharmacological activity. Drug Des Devel Ther. 2025; 19: 5663-84, CrossRef.
Budiman A, Citraloka ZG, Muchtaridi M, Sriwidodo S. Inhibition of crystal nucleation and growth in aqueous drug solutions: Impact of different polymers on the supersaturation profiles of amorphous drugs - The case of alpha-mangostin. Pharmaceutics. 2022; 14(2386): 2386, CrossRef.
Park CW, Tung NT, Rhee YS, Kim JY, Oh TO, Ha JM, et al. Physicochemical, pharmacokinetic and pharmacodynamic evaluations of novel ternary solid dispersion of rebamipide with poloxamer 407. Drug Dev Ind Pharm. 2013; 39(6): 836-44, CrossRef.
Munir R, Hadi A, Khan SUD, Asghar S, Irfan M, Khan IU, et al. Solubility and dissolution enhancement of dexibuprofen with hydroxypropylbetacyclodextrin (HPβCD) and poloxamers (188/407) inclusion complexes: Preparation and in vitro characterization. Polymers. 2022; 14(3): 579, CrossRef.
Greenspan L. Humidity Fixed Points of Binary Saturated Aqueous Solutions. J Res Natl Bur Stand A Phys Chem. 1977; 81A(1): 89-96, CrossRef.
Baird JA, Van Eerdenbrugh B, Taylor LS. A classification system to assess the crystallization tendency of organic molecules from undercooled melts. J Pharm Sci. 2010; 99(9): 3787-806, CrossRef.
Budiman A, Aulifa DL. A comparative study of the pharmaceutical properties between amorphous drugs loaded-mesoporous silica and pure amorphous drugs prepared by solvent evaporation. Pharmaceuticals. 2022; 15(6): 730, CrossRef.
Budiman A, Nurani NV, Laelasari E, Muchtaridi M, Sriwidodo S, Aulifa DL. Effect of drug-polymer interaction in amorphous solid dispersion on the physical stability and dissolution of drugs: The case of alpha-mangostin. Polymers. 2023; 15(14): 3034, CrossRef.
Salamah R, Wijayanti N, Widiyanto S. n-hexane fraction of Cucumis melo L. cultivar gama melon parfum: An in vitro study in MCF7 and T47D cells line. Mol Cell Biomed Sci. 2025; 9(2): 76-81, CrossRef.
Budiman A, Handini AL, Muslimah MN, Nurani NV, Laelasari E, Kurniawansyah IS, et al. Amorphous solid dispersion as drug delivery vehicles in cancer. Polymers. 2023; 15(16): 3380, CrossRef.
Shah N, Iyer RM, Mair HJ, Choi DS, Tian H, Diodone R, et al. Improved human bioavailability of vemurafenib, a practically insoluble drug, using an amorphous polymer-stabilized solid dispersion prepared by a solvent-controlled coprecipitation process. J Pharm Sci. 2013; 102(3): 967-81, CrossRef.
Rizal MI, Sandra F. Brucea javanica leaf rxtract activates caspase-9 and caspase-3 of mitochondrial apoptotic pathway in human oral squamous cell carcinoma. Indones Biomed J. 2016; 8(1): 43-8, CrossRef.
Alkathiri FA, Bukhari SI, Imam SS, Alshehri S, Mahdi WA. Formulation of silymarin binary and ternary solid dispersions: Characterization, simulation study and cell viability assessment against lung cancer cell line. Heliyon. 2024; 10(1): e23221, CrossRef.
Widowati W, Jasaputra DK, Sumitro SB, Widodo MA, Afifah E, Rizal R, et al. Direct and indirect effect of TNFα and IFNγ toward apoptosis in breast cancer cells. Mol Cell Biomed Sci. 2018; 2(2): 60-9, CrossRef.
Haq SA, Paudwal G, Banjare N, Iqbal Andrabi N, Wazir P, Nandi U, et al. Sustained release polymer and surfactant based solid dispersion of andrographolide exhibited improved solubility, dissolution, pharmacokinetics, and pharmacological activity. Int J Pharm. 2024; 651: 123786, CrossRef.
Mane PT, Wakure BS, Wakte PS. Ternary inclusion complex of docetaxel using β-cyclodextrin and hydrophilic polymer: Physicochemical characterization and in-vitro anticancer activity. J Appl Pharm Sci. 2022; 12(12): 150-61, CrossRef.
Copetti PM, Bissacotti BF, da Silva Gündel S, Bottari NB, Sagrillo MR, Machado AK, et al. Pharmacokinetic profiles, cytotoxicity, and redox metabolism of free and nanoencapsulated curcumin. J Drug Deliv Sci Technol. 2022; 72: 103352, CrossRef.
Chung CK, Fransen MF, van der Maaden K, Campos Y, García-Couce J, Kralisch D, et al. Thermosensitive hydrogels as sustained drug delivery system for CTLA-4 checkpoint blocking antibodies. J Control Release. 2020: 323: 1-11, CrossRef.
Iyer R, Jovanovska VP, Berginc K, Jaklic M, Fabiani F, Harlacher C, et al. Amorphous solid dispersions (ASDs): the influence of material properties, manufacturing processes and analytical technologies in drug product development. Pharmaceutics. 2021; 13(10): 1682, CrossRef.
Holm TP, Kokott M, Knopp MM, Boyd BJ, Berthelsen R, Quodbach J, et al. Development of a multiparticulate drug delivery system for in situ amorphisation. Eur J Pharm Biopharm. 2022; 180: 170-80, CrossRef.
DOI: https://doi.org/10.18585/inabj.v18i1.3938
Copyright (c) 2026 The Prodia Education and Research Institute
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Indexed by:
The Prodia Education and Research Institute
