Fabrication of α-mangostin – loaded liposomes for cytotoxic-activity against A549 lung-cancer spheroids

Tran Dinh Thiet; Pham Thu Uyen; Nguyen Thanh Duong

doi:10.15625/2525-2518/17524

Author affiliations

Authors

Tran Dinh Thiet High School of Education Sciences, University of Education, Vietnam National University, Hanoi (VNU), 144 Xuan Thuy Street, Cau Giay District, Ha Noi, Viet Nam
Pham Thu Uyen Institute for Tropical Technology, Vietnam Academy of Science and Technology (VAST),18 Hoang Quoc Viet Street, Cau Giay District, Ha Noi, Viet Nam; University of Science and Technology of Hanoi (USTH), 18 Hoang Quoc Viet Street, Cau Giay District, Ha Noi, Viet Nam
Nguyen Thanh Duong Institute for Tropical Technology, Vietnam Academy of Science and Technology (VAST),18 Hoang Quoc Viet Street, Cau Giay District, Ha Noi, Viet Nam

DOI:

https://doi.org/10.15625/2525-2518/17524

Keywords:

liposome, A549, α-mangostin, DLS, 3D cell culture

Abstract

α-mangostin is a natural product isolated from the mangosteen pericarps with diverse biological activities, including cytotoxicity against cancer cells. However, the application of α-mangostin in cancer treatment is limited due to the high cytotoxicity and poor solubility in water. In this research, we fabricated α-mangostin-loaded liposomes from soybean lecithin and cholesterol to enhance the solubility in water of α-mangostin and reduce side effects in the treatment of cancer. The liposomal membrane uses Soybean Lecithin (SBL) as a phospholipid and Tocopherol (Toc) as a stabilizer, at 4 ratios of SBL/Toc are 1/1, 2/1, 4/1, 8/1. Experimental results showed that liposomes with SBL/Toc molar ratio of 4/1 had a mean size value of 105.8 ± 3.9 nm, and a polydispersity index (PDI) of 0.149. The encapsulation efficiency was 51.3 %. We believe that this formulation has the potential to be developed into an improved drug delivery system for α-mangostin. The lung carcinoma epithelial cells (A549) were cultured in microwell for 14 days to form spheroids. Then, spheroids were probed with a concentration of α-mangostin-loaded liposomes of 10 µM. The results showed the ability to significantly reduce cell viability after 36 hours of testing.

Downloads

Download data is not yet available.

References

Rao L., Chen W., Li M., Xiao B., Fu J., Zeng X., Cai Y., and Xie D. - Increased Intratumoral Neutrophil in Colorectal Carcinomas Correlates Closely with Malignant Phenotype and Predicts Patients' Adverse Prognosis, PLOS ONE 7 (1) (2012) e30806. doi: https://doi.org/ 10.1371/journal.pone.0030806 DOI: https://doi.org/10.1371/journal.pone.0030806

“Global health estimates: Leading causes of death.” https://www.who.int/data/ gho/data/themes/mortality-and-global-health-estimates/ghe-leading-causes-of-death (accessed Sep. 19, 2022).

Peres V., Nagem T. J., and de Oliveira F. F. - Tetraoxygenated naturally occurring xanthones, Phytochemistry 55 (7) (2000) 683-710, doi: 10.1016/S0031-9422(00)00303-4. DOI: https://doi.org/10.1016/S0031-9422(00)00303-4

Hafeez B. B., Mustafa A., Fischer J. W., Singh A. K., Zhong W., Shekhani M. O., Meske L., Havighurst T. C., Kim K., and Verma A. K. - α-Mangostin: A Dietary Antioxidant Derived from the Pericarp of Garcinia mangostana L. Inhibits Pancreatic Tumor Growth in Xenograft Mouse Model, Antioxidants &Amp; Redox Signaling 21 (5) (2014) 682-699. doi: 10.1089/ars.2013.5212 DOI: https://doi.org/10.1089/ars.2013.5212

Nguemfo E. L., Dimo T., Dongmo A. B., Azebaze A. G. B., Alaoui K., Asongalem A. E., ... and Kamtchouing P. - Anti-oxidative and anti-inflammatory activities of some isolated constituents from the stem bark of Allanblackia monticola Staner LC (Guttiferae), Inflammopharmacology 17 (1) (2009) 37-41. doi: https://doi.org/10.1007/s10787-008-8039-2 DOI: https://doi.org/10.1007/s10787-008-8039-2

Iikubo K., Ishikawa Y., Ando N., Umezawa K., and Nishiyama S. - The first direct synthesis of α-mangostin, a potent inhibitor of the acidic sphingomyelinase, Tetrahedron letters 43 (2) (2002) 291-293. doi: 10.1016/S0040-4039(01)02137-2. DOI: https://doi.org/10.1016/S0040-4039(01)02137-2

Shibata M. A., Iinuma M., Morimoto J., Kurose H., Akamatsu K., Okuno Y., and Otsuki Y. - α-Mangostin extracted from the pericarp of the mangosteen (Garcinia mangostanaLinn) reduces tumor growth and lymph node metastasis in an immunocompetent xenograft model of metastatic mammary cancer carrying a p53 mutation, BMC medicine 9 (1) (2011) 1-18. doi:10.1186/1741-7015-9-69. DOI: https://doi.org/10.1186/1741-7015-9-69

Lei J, Huo X, Duan W et al. - α-Mangostin inhibits hypoxia-driven ROS-induced PSC activation and pancreatic cancer cell invasion. Cancer Lett. 347 (1) (2014) 129-138. doi:10.1016/j.canlet.2014.02.003. DOI: https://doi.org/10.1016/j.canlet.2014.02.003

Kritsanawong S., Innajak S., Imoto M., and Watanapokasin, R. - Antiproliferative and apoptosis induction of α-mangostin in T47D breast cancer cells, International Journal of oncology 48 (5) (2016) 2155-2165. doi: 10.3892/ijo.2016.3399. DOI: https://doi.org/10.3892/ijo.2016.3399

Li G., Petiwala S. M., Nonn L., & Johnson J. J. - Inhibition of CHOP accentuates the apoptotic effect of α-mangostin from the mangosteen fruit (Garcinia mangostana) in 22Rv1 prostate cancer cells, Biochemical and Biophysical Research Communications 453 (1) (2014) 75-80. https://doi.org/10.1016/j.bbrc.2014.09.054. DOI: https://doi.org/10.1016/j.bbrc.2014.09.054

Wathoni N., Rusdin A., Motoyama K., Joni I. M., Lesmana R., and Muchtaridi M. - Nanoparticle Drug Delivery Systems for α-Mangostin, Nanotechnology, Science and Applications 13 (2020) 23-36. https://doi.org/10.2147/nsa.s243017. DOI: https://doi.org/10.2147/NSA.S243017

De S L Oliveira A. L. C., Schomann T., De Geus-Oei L., Kapiteijn E., Cruz, L. J., and De Araújo, R. F. - Nanocarriers as a tool for the treatment of colorectal cancer, Pharmaceutics 13 (8) (2021) 1321. https://doi.org/10.3390/pharmaceutics13081321. DOI: https://doi.org/10.3390/pharmaceutics13081321

Zhang K., Gu Q., Yang K., Ming X., and Wang J. - Anticarcinogenic effects of Α-Mangostin: a review, Planta Medica 83 (03/04) (2016) 188-202. https://doi.org/10.1055/s-0042-119651. DOI: https://doi.org/10.1055/s-0042-119651

Shaheen S. M., Shakil Ahmed F. R., Hossen M. N., Ahmed M., Amran M. S., and Ul-Islam M. A. - Liposome as a carrier for advanced drug delivery, Pak. J. Biol. Sci. 9 (6) (2006) 1181-1191. DOI: https://doi.org/10.3923/pjbs.2006.1181.1191

Sercombe L., Veerati T., Moheimani F., Wu S., Sood A., and Hua S. - Advances and Challenges of Liposome Assisted Drug Delivery, Frontiers In Pharmacology 286 (6) (2015). doi: 10.3389/fphar.2015.00286 DOI: https://doi.org/10.3389/fphar.2015.00286

Alavi M., Karimi N., and Safaei M. - Application of various types of liposomes in drug delivery systems, Advanced Pharmaceutical Bulletin 7 (1) (2017) 3-9. doi: https://doi.org/10.15171/apb.2017.002. DOI: https://doi.org/10.15171/apb.2017.002

Chin G. S., Todo H., Kadhum W. R., Hamid M. A., and Sugibayashi K. - In vitro permeation and skin retention of α-mangostin proniosome, Chemical and pharmaceutical bulletin 64 (12) (2016) 1666-1673. doi: 10.1248/cpb.c16-00425. DOI: https://doi.org/10.1248/cpb.c16-00425

Hong S. C., Park K. M., Hong C. R., Kim J. C., Yang S. H., Yu H. S., and Chang P. S. - Microfluidic assembly of liposomes dual-loaded with catechin and curcumin for enhancing bioavailability, Colloids and Surfaces A: Physicochemical and Engineering Aspects 594 (2020) 124670. doi: 10.1016/j.colsurfa.2020.124670. DOI: https://doi.org/10.1016/j.colsurfa.2020.124670

Zyriax B. C., and Windler E. - Dietary fat in the prevention of cardiovascular disease—a review. European Journal of Lipid Science and Technology, 102 (5) (2000) 355-365. doi: https://doi.org/10.1002/(SICI)1438-9312(200005)102:5<355::AID-EJLT355>3.0.CO;2-3. DOI: https://doi.org/10.1002/(SICI)1438-9312(200005)102:5<355::AID-EJLT355>3.0.CO;2-3

Nicholson A. M., and Ferreira A. - Cholesterol and neuronal susceptibility to beta-amyloid toxicity. Cognitive sciences 5 (1) (2010) 35. https://www.ncbi.nlm.nih.gov/ pmc/articles/PMC4203449/

Xin J., Tang J., Bu M., Sun Y., Wang X., Wu L., and Liu H. - A novel eye drop of alpha tocopherol to prevent ocular oxidant damage: improve the stability and ocular efficacy, Drug Development and Industrial Pharmacy 42 (4) (2016) 525-534. doi:10.1016/ j.febslet.2008.10.002. DOI: https://doi.org/10.3109/03639045.2015.1082582

Hincha D. - Effects of α-tocopherol (vitamin E) on the stability and lipid dynamics of model membranes mimicking the lipid composition of plant chloroplast membranes, FEBS Lett. 582 (25-26) (2008) 3687-3692. https://doi.org/10.1016/j.febslet.2008.10.002 DOI: https://doi.org/10.1016/j.febslet.2008.10.002

Tabandeh, H., and Mortazavi S. A. - An investigation into some effective factors on encapsulation efficiency of alpha-tocopherol in MLVs and the release profile from the corresponding liposomal gel, Iranian journal of pharmaceutical research: IJPR 12 (Suppl) (2013) 21. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3813372/

Trang Phan T. K., Tran T. Q., Nguyen Pham D. T., and Nguyen, D. T. - Characterization, Release Pattern, and Cytotoxicity of Liposomes Loaded With α-Mangostin Isolated from Pericarp of Mangosteen (Garcinia mangostana L.), Natural Product Communications 15 (11) (2020) 1934578X20974559. doi: 10.1177/1934578X20974559 DOI: https://doi.org/10.1177/1934578X20974559

Lee S., and Griffiths J. R. - How and Why Are Cancers Acidic? Carbonic Anhydrase IX and the Homeostatic Control of Tumour Extracellular pH. Cancers, 12 (6) (2020) 1616. https://doi.org/10.3390/cancers12061616. DOI: https://doi.org/10.3390/cancers12061616

Moeller H., Mian M. K., Shrivastava S., Chung B. G., and Khademhosseini, A. - A microwell array system for stem cell culture, Biomaterials 29 (6) (2008) 752-763. https://doi.org/10.1016/j.biomaterials.2007.10.030. DOI: https://doi.org/10.1016/j.biomaterials.2007.10.030

Yuk H., Zhang T., Lin S., Parada G. A., and Zhao X. - Tough bonding of hydrogels to diverse non-porous surfaces, Nature Materials 15 (2) (2015) 190-196. https://doi.org/ 10.1038/nmat4463. DOI: https://doi.org/10.1038/nmat4463

Liu T., Chien C., Parkinson L., and Thierry, B. - Advanced micromachining of concave microwells for long term On-Chip culture of multicellular tumor spheroids, ACS Applied Materials & Interfaces 6 (11) (2014) 8090-8097. https://doi.org/10.1021/am500367h. DOI: https://doi.org/10.1021/am500367h

Thomsen A. R., Aldrian C., Bronsert P., Thomann Y., Nanko N., Melin N., ... and Lund P. G. - A deep conical agarose microwell array for adhesion independent three-dimensional cell culture and dynamic volume measurement, Lab on a chip 18 (1) (2018) 179-189. doi:10.1039/c7lc00832e. DOI: https://doi.org/10.1039/C7LC00832E

Liu Y., Bravo K. M. C., and Liu J. - Targeted liposomal drug delivery: a nanoscience and biophysical perspective, Nanoscale Horizons 6 (2) (2021) 78-94. https://doi.org/ 10.1039/d0nh00605j. DOI: https://doi.org/10.1039/D0NH00605J

Chen Z. L., Huang M., Wang X. R., Fu J., Han M., Shen Y. Q., Zheng X., and Gao, J. Q. - Transferrin-modified liposome promotes α-mangostin to penetrate the blood–brain barrier, Nanomedicine: Nanotechnology, Biology and Medicine 12 (2) (2016) 421-430. doi: https://doi.org/10.1016/j.nano.2015.10.021. DOI: https://doi.org/10.1016/j.nano.2015.10.021