Liposomal Formulation of Plant Based Natural Photosensitisers for Thrombosis
Abstract
Photothermal and photodynamic therapy (PTPDT) in medical field continue to evolve due to their relatively low adverse effect and high efficiency for therapeutic application. Photosensitisers compounds have shown excellent ability in inducing mild hyperthermia and generation of reactive oxygen species (ROS) which is beneficial for thrombolysis. Herein, we explored plant-based sources rich in pigments such as beet root (BR), butterfly pea flower (BPF), red cabbage (RC), purple sweet potato (PSP) and phycocyanin (PHY) as natural photosensitisers (NPS) candidates for the treatment of thrombosis. We were able to produce extracts with strong absorption within the 400-800 nm wavelength range, the ideal window for photosensitisation. The photosensitising ability of the NPS were confirmed after significant photothermal increase was achieved after 5 minutes low intensity exposure with 450 nm and 550 nm lasers. Extract from BPF, RC, BR and PHY were the most promising and further formulated into liposomes. Through in vitro thrombolytic activity on human blood clots, we confirmed thrombolytic capability of NPS comparable to that of nattokinase. Liposomal formulation of the best NPS (Lip-PHY and Lip-BPF) produced particles of ~168.3 and 215.9 nm respectively, with good encapsulation efficiency and stability. Ultimately with this study, we have demonstrated liposomal formulation of NPs and their strong potential as thrombolytic agent.
References
Bernstein, A., & Noreña, C. P. Z. (2017). Kinetics of enzymatic inactivation and loss of anthocyanins and antioxidant activity in red cabbage blanched under different conditions. Journal of Food Biochemistry, 41(3). doi:10.1111/jfbc.12340
Chaniago, R., Indriasari, Y., Berlian, M., & Basrin, F. (2022). ANTHOCYANIN LEVELS AND ANTIOXIDANT ACTIVITY OF TORTILLA PURPLE SWEET POTATO (Ipomoea batatas L). AGROLAND The Agricultural Sciences Journal (e-Journal), 8(2), 132-143. doi:10.22487/agroland.v8i2.692
Chen, C. C., Lin, C., Chen, M. H., & Chiang, P. Y. (2019). Stability and Quality of Anthocyanin in Purple Sweet Potato Extracts. Foods, 8(9). doi:10.3390/foods8090393
de Moraes Nogueira, A. O., Felipe Kokuszi, L. T., Poester Cordeiro, A., Ziebell Salgado, H., Costa, J. A. V., Santos, L. O., & de Lima, V. R. (2021). Spirulina sp. LEB 18-extracted phycocyanin: Effects on liposomes' physicochemical parameters and correlation with antiradical/antioxidant properties. Chem Phys Lipids, 236, 105064. doi:10.1016/j.chemphyslip.2021.105064
Fithri, N. A., Mardiyanto, M., Fitrya, F., Rahmah, A., & Annisa, N. M. (2024). Formulation and Evaluation of Gambier (Uncaria gambir)-Chitosan Microparticle Intranasal Delivery for Alzheimer’s Diseases. Science and Technology Indonesia, 9(2), 284-298. doi:10.26554/sti.2024.9.2.284-298
Fithri, N. A., Wu, Y., Cowin, G., Akther, F., Tran, H. D. N., Tse, B., . . . Ta, H. T. (2023). Gold-iron oxide nanoparticle: A unique multimodal theranostic approach for thrombosis. Applied Materials Today, 31. doi:10.1016/j.apmt.2023.101750
Gao, Z., Yamashita, D., Matsumoto, Y., Tamaoki, Y., Ueda, Y., Okada, H., . . . Umemura, K. (2022). In vitro analysis of mechanism of pulsed-laser thrombolysis. Plos One, 17(1). doi:10.1371/journal.pone.0262991
Ghareaghajlou, N., Hallaj-Nezhadi, S., & Ghasempour, Z. (2021). Red cabbage anthocyanins: Stability, extraction, biological activities and applications in food systems. Food Chem, 365, 130482. doi:10.1016/j.foodchem.2021.130482
Ghosh, S., Carter, K. A., & Lovell, J. F. (2019). Liposomal formulations of photosensitizers. Biomaterials, 218, 119341. doi:10.1016/j.biomaterials.2019.119341
Gonzalez Gomez, A., Syed, S., Marshall, K., & Hosseinidoust, Z. (2019). Liposomal Nanovesicles for Efficient Encapsulation of Staphylococcal Antibiotics. ACS Omega, 4(6), 10866-10876. doi:10.1021/acsomega.9b00825
Guine, R. P. F., Goncalves, F., Lerat, C., El Idrissi, T., Rodrigo, E., Correia, P. M. R., & Goncalves, J. C. (2018). Extraction of Phenolic Compounds with Antioxidant Activity from Beetroot (Beta vulgaris L.). Current Nutrition & Food Science, 14(4), 350-357. doi:10.2174/1573401313666170609102336
Jiang, D., Liu, G., Yang, B., Niu, H., Fan, H., Ren, Z., . . . He, D. (2023). 450-nm blue diode laser: a novel medical apparatus for upper tract urothelial lesions. World J Urol, 41(12), 3773-3779. doi:10.1007/s00345-023-04647-x
Kubrak, T. P., Kolodziej, P., Sawicki, J., Mazur, A., Koziorowska, K., & Aebisher, D. (2022). Some Natural Photosensitizers and Their Medicinal Properties for Use in Photodynamic Therapy. Molecules, 27(4). doi:10.3390/molecules27041192
Mattioli, R., Francioso, A., Mosca, L., & Silva, P. (2020). Anthocyanins: A Comprehensive Review of Their Chemical Properties and Health Effects on Cardiovascular and Neurodegenerative Diseases. Molecules, 25(17). doi:10.3390/molecules25173809
Oliveira, H., Correia, P., Pereira, A. R., Araujo, P., Mateus, N., de Freitas, V., . . . Fernandes, I. (2020). Exploring the Applications of the Photoprotective Properties of Anthocyanins in Biological Systems. Int J Mol Sci, 21(20). doi:10.3390/ijms21207464
Polat, E., & Kang, K. (2021). Natural Photosensitizers in Antimicrobial Photodynamic Therapy. Biomedicines, 9(6). doi:10.3390/biomedicines9060584
Refaat, A., del Rosal, B., Palasubramaniam, J., Pietersz, G., Wang, X., Peter, K., & Moulton, S. E. (2021). Smart Delivery of Plasminogen Activators for Efficient Thrombolysis; Recent Trends and Future Perspectives. Advanced Therapeutics, 4(6). doi:10.1002/adtp.202100047
Stark, B., Pabst, G., & Prassl, R. (2010). Long-term stability of sterically stabilized liposomes by freezing and freeze-drying: Effects of cryoprotectants on structure. Eur J Pharm Sci, 41(3-4), 546-555. doi:10.1016/j.ejps.2010.08.010
Tuan Putra, T. N. M., Zainol, M. K., MohdIsa, N. S., & MohdMaidin, N. (2021). Chemical characterization of ethanolic extract of Butterfly pea flower (Clitoriaternatea). Food Research, 5(4), 127-134. doi:10.26656/fr.2017.5(4).744
Vazquez-Prada, K. X., Moonshi, S. S., Xu, Z. P., & Ta, H. T. (2023). Photothermal nanomaterials for theranostics of atherosclerosis and thrombosis. Applied Materials Today, 35. doi:10.1016/j.apmt.2023.101967
Vidana Gamage, G. C., Lim, Y. Y., & Choo, W. S. (2021). Anthocyanins From Clitoria ternatea Flower: Biosynthesis, Extraction, Stability, Antioxidant Activity, and Applications. Front Plant Sci, 12, 792303. doi:10.3389/fpls.2021.792303
Wood, K., Stephens, S. E., Xu, F., Hazaa, A., Meek, J. C., Jensen, H. K., . . . Wickramasinghe, R. (2022). In Vitro Blood Clot Formation and Dissolution for Testing New Stroke-Treatment Devices. Biomedicines, 10(8). doi:10.3390/biomedicines10081870
Zhao, X., Liu, J., Fan, J., Chao, H., & Peng, X. (2021). Recent progress in photosensitizers for overcoming the challenges of photodynamic therapy: from molecular design to application. Chem Soc Rev, 50(6), 4185-4219. doi:10.1039/d0cs00173b
Zhou, H., Pan, H., Raza, F., Zafar, H., Ge, Y., Wang, N., . . . Yang, Y. (2024). Thermosensitive drug-loaded liposomes for photothermal and chemotherapeutic treatment of colon cancer. Materials Advances, 5(6), 2456-2469. doi:10.1039/d3ma01060k
Zhu, Z., Guan, Q., Koubaa, M., Barba, F. J., Roohinejad, S., Cravotto, G., . . . He, J. (2017). HPLC-DAD-ESI-MS(2) analytical profile of extracts obtained from purple sweet potato after green ultrasound-assisted extraction. Food Chem, 215, 391-400. doi:10.1016/j.foodchem.2016.07.157
Zia, P., Sunita, M., & Sneha, S. (2021). Extraction of Natural Colour from Beet Root (Beta vulgaris) its Phytochemical Analysis and Antibacterial Activity. EAS Journal of Nutrition and Food Sciences, 3(4), 80-85. doi:10.36349/easjnfs.2021.v03i04.002


