Preparation, Optimization and in vitro Studies of Spectrin Decorated Liposomes: A Promising Strategy for Cancer Treatment Spectrin anchored liposomes for treatment of cancer
Trends in Peptide and Protein Sciences,
Vol. 6 (2021),
24 Esfand 2021
,
Page 1-15 (e6)
https://doi.org/10.22037/tpps.v6i.36423
Abstract
The distorted membrane asymmetry and abnormal distribution of phospholipids viz. phosphatidylserine (PS) and phosphatidylethanolamine (PE), in the outer leaflet are one of the critical features of cancer. It is a much-known fact that protein, such as spectrin (SPC), has an affinity towards the PS and PE. Hence, SPC was used to target exposed PS and PE of cancer cells. In the present study, the drug Methotrexate was used because it disrupts and fluidized the plasma membrane. Liposomes prepared and optimized by the Response Surface Box Behnken randomized model using various independent and dependent variables. The optimized liposomes were further coated with SPC and the coating confirmed by infrared spectroscopy. Both formulations were further characterized for vesicle size, entrapment efficiency (EE), zeta potential, surface morphology, and percentage of drug released. The results indicate that the prepared formulations were in spherical, nano-metric size with negative zeta potential and more than 75% drug entrapment with sustained release pattern. The concentration for 50% of maximal inhibition of cell proliferation (GI50) in U373-MG cells was found to be 24.11±0.44 and 3.90±0.19 µg/mL of the formulations MTX-LP2 and SPC-MTX-LP2, respectively. Briefly, results suggest that the developed liposomes could be used for enhanced cancer treatment.
HIGHLIGHTS
- Optimization of liposomes using Design of Experiment.
- Drug sustained released from liposomes and followed a non-Fickian diffusion anomalous transport.
- Spectrin-liposomes target the exposed membrane phospholipids of cancer cells.
- Spectrin decorated liposomes showed 50% of maximal inhibition of cell proliferation in U373-MG cells more significant plain liposomes.
- Spectrin
- spectrin liposomes
- phosphatidylserine
- phosphatidylethanolamine
- tumor membrane targeting
- Design of Experiment
How to Cite
References
Akbarzadeh, A., Rezaei-Sadabady, R., Davaran, S., Joo, S.W., Zarghami, N., Hanifehpour, Y., Samiei, M., Kouhi, M. and K. Nejati-Koshki, (2013). "Liposome: classification, preparation, and applications." Nanoscale Research Letters, 8(1): 102. doi:10.1186/1556-276X-8-102.
Alekseeva, A.A., Moiseeva, E.V., Onishchenko, N.R., Boldyrev, I.A., Singin, A.S., Budko, A.P., Shprakh, Z.S., Molotkovsky, J.G. and E.L. Vodovozova, (2017). "Liposomal formulation of a methotrexate lipophilic prodrug: assessment in tumor cells and mouse T-cell leukemic lymphoma." International Journal of Nanomedicine, 12: 3735-3749. doi:10.2147/IJN.S133034.
Alves, A. C., Ribeiro, D., Nunes, C. and S. Reis, (2016). "Biophysics in cancer: The relevance of drug-membrane interaction studies." Biochim Biophys Acta Biomembr, 1858(9): 2231-2244. doi:10.1016/j.bbamem.2016.06.025.
Costa, P. and J. M. S. Lobo, (2001). "Modeling and comparison of dissolution profiles." European Journal of Pharmaceutical Sciences, 13(2): 123-133. doi:10.1016/s0928-0987(01)00095-1.
Desai, T. J., Toombs, J. E., Minna, J. D., Brekken, R. A. and D. G. Udugamasooriya, (2016). "Identification of lipid-phosphatidylserine (PS) as the target of unbiasedly selected cancer specific peptide-peptoid hybrid PPS1." Oncotarget, 7(21): 30678-30690. doi:10.18632/oncotarget.8929.
Dubey, P. K., Mishra, V., Jain, S., Mahor, S. and S. P. Vyas, (2004). "Liposomes modified with cyclic RGD peptide for tumor targeting." Journal of Drug Targeting, 12(5): 257-264. doi:10.1080/10611860410001728040.
Ejikeme, P. C. N., Ejikeme, M. E. and B. N. Abalu, (2013). "RSM optimization process for uptake of water from ethanol water solution using oxidized starch." The Pacific Journal of Science and Technology, 14: 319-329.
Elvas, F., Stroobants, S. and L. Wyffels, (2017). "Phosphatidylethanolamine targeting for cell death imaging in early treatment response evaluation and disease diagnosis." Apoptosis, 22(8): 971-987. doi:10.1007/s10495-017-1384-0.
Emoto, K., Toyama-Sorimachi, N., Karasuyama, H., Inoue, K. and M. Umeda, (1997). "Exposure of phosphatidylethanolamine on the surface of apoptotic cells." Experimental Cell Research, 232(2): 430-434. doi:10.1006/excr.1997.3521.
Fadok, V. A., Voelker, D. R., Campbell, P. A., Cohen, J. J., Bratton, D. L. and P. M. Henson, (1992). "Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages." Journal of Immunology, 148(7): 2207-2216. doi:10.1007/s13238-010-0076-0.
Ferreira, S. L., Bruns R. E., Ferreira, H. S., Matos, G. D., David, J. M., Brandão, G. C., da Silva, E. G., Portugal, L. A., dos Reis, P. S., Souza, A. S. and W. N. dos Santos, (2007). "Box-Behnken design: an alternative for the optimization of analytical methods." Analytica Chimica Acta, 597(2): 179-86. doi: 10.1016/j.aca.2007.07.011.
Fry, D. W., White, J. C. and I. D. Goldman, (1979). "Alterations of the carrier-mediated transport of an anionic solute, methotrexate, by charged liposomes in Ehrlich ascites tumor cells." Journal of Membrane Biology, 50(2): 123-140. doi:10.1007/bf01868944.
García-Beleño, J. and E. Rodríguez de San Miguel, (2021). "Integration of Response Surface Methodology (RSM) and Principal Component Analysis (PCA) as an optimization tool for polymer inclusion membrane based-optodes designed for Hg(II), Cd(II), and Pb(II)." Membranes, 11: 288. doi: 10.3390/membranes11040288.
Gottschalk, O., Metz, P., Dao Trong, M. L., Altenberger, S., Jansson, V., Mutschler, W. and M. Schmitt-Sody, (2015). "Therapeutic effect of methotrexate encapsulated in cationic liposomes (EndoMTX) in comparison to free methotrexate in an antigen-induced arthritis study in vivo." Scandinavian Journal of Rheumatology, 44(6): 456-463. doi:10.3109/03009742.2015.1030448.
Grzybek, M., Chorzalska, A., Bok, E., Hryniewicz-Jankowska, A., Czogalla, A., Diakowski, W. and A. F. Sikorski, (2006). "Spectrin–phospholipid interactions: Existence of multiple kinds of binding sites?" Chemistry and Physics of Lipids, 141(1-2): 133-141. doi:10.1016/j.chemphyslip.2006.02.008.
Gutschner, T. and S. Diederichs, (2012). "The hallmarks of cancer: a long non-coding RNA point of view." RNA Biology, 9(6): 703-719. doi:10.4161/rna.20481.
Haider, T., Pandey, V., Behera, C., Kumar, P., Gupta, P. N. and V. Soni, (2020). "Spectrin conjugated PLGA nanoparticles for potential membrane phospholipid interactions: Development, optimization and in vitro studies." Journal of Drug Delivery Science and Technology, 60: 102087. doi:10.1016/j.jddst.2020.102087.
Haider, T., Tiwari, R., Vyas, S. P. and V. Soni, (2019). "Molecular determinants as therapeutic targets in cancer chemotherapy: An update." Pharmacology & Therapeutics, 200: 85-109. doi:10.1016/j.pharmthera.2019.04.011
Jain, S. K., Haider, T., Kumar, A. and A. Jain, (2016). "Lectin-conjugated clarithromycin and acetohydroxamic acid-loaded plga nanoparticles: a novel approach for effective treatment of H pylori." AAPS PharmSciTech, 17(5): 1131-1140. doi:10.1208/s12249-015-0443-5.
Jin, S., DiPaola, R. S., Mathew, R. and E. White, (2007). "Metabolic catastrophe as a means to cancer cell death." Journal of Cell Science, 120(3): 379-383. doi:10.1242/jcs.03349.
Joseph, E. and G. Singhvi, (2019). "Multifunctional nanocrystals for cancer therapy: a potential nanocarrier." In: A. M. Grumezescu (Ed.), Nanomaterials for Drug Delivery and Therapy, William Andrew Publishing, pp. 91-116.
Korgel, B. A., van Zanten, J. H. and H. G. Monbouquette, (1998). "Vesicle size distributions measured by flow field-flow fractionation coupled with multiangle light scattering." Biophysical Journal, 74(6): 3264-3272. doi:10.1016/S0006-3495(98)78033-6.
Lakkadwala, S., dos Santos Rodrigues, B., Sun, C. and J. Singh, (2019). "Dual functionalized liposomes for efficient co-delivery of anti-cancer chemotherapeutics for the treatment of glioblastoma." Journal of Controlled Release, 307: 247-260. doi:https://doi.org/10.1016/j.jconrel.2019.06.033.
Lujan, H., Griffin, W. C., Taube, J. H. and C. M. Sayes, (2019). "Synthesis and characterization of nanometer-sized liposomes for encapsulation and microRNA transfer to breast cancer cells." International Journal of Nanomedicine, 14: 5159-5173. doi:10.2147/IJN.S203330.
Machnicka, B., Grochowalska, R., Boguslawska, D. M., Sikorski, A. F. and M. C. Lecomte, (2012). "Spectrin-based skeleton as an actor in cell signaling." Cellular and Molecular Life Sciences, 69(2): 191-201. doi:10.1007/s00018-011-0804-5.
Maheswari, K. U. (2001). "Lipid bilayer–methotrexate interactions: A basis for methotrexate neurotoxicity." Current Science, 81(4): 571-574.
Malam, Y., Loizidou, M. and A. M. Seifalian, (2009). "Liposomes and nanoparticles: nanosized vehicles for drug delivery in cancer." Trends in Pharmacological Sciences, 30(11): 592-599. doi:https://doi.org/10.1016/j.tips.2009.08.004.
Manojlovic, V., Winkler, K., Bunjes, V., Neub, A., Schubert, R., Bugarski, B. and G. Leneweit, (2008). "Membrane interactions of ternary phospholipid/cholesterol bilayers and encapsulation efficiencies of a RIP II protein." Colloids and Surfaces B: Biointerfaces, 64(2): 284-296. doi:10.1016/j.colsurfb.2008.02.001.
Myers, R.H., Montgomery, D.C. and C.M. Anderson-Cook, (2016). "Response surface methodology: process and product optimization using designed experiments." John Wiley & Sons “New York, NY, USA, p. 856; ISBN 978-1-118-91601-8.
Mizuguchi, M., Nara, M., Kawano, K. and K. Nitta, (1997). "FT‐IR study of the Ca2+‐binding to bovine α‐lactalbumin: Relationships between the type of coordination and characteristics of the bands due to the Asp COO− groups in the Ca2+‐binding site." FEBS Letters, 417(1): 153-156. doi:10.1016/S0014-5793(97)01274-X.
Mombers, C., de Gier, J., Demel, R. A. and L. L. van Deenen, (1980). "Spectrin-phospholipid interaction: A monolayer study." Biochimica et Biophysica Acta, 603(1): 52-62. doi:10.1016/0005-2736(80)90390-9.
Mozafari, M. (2010). "Nanoliposomes: preparation and analysis." (In V. Weissig (Ed.), Liposomes. Methods in Molecular Biology (Methods and Protocols), Humana Press. 605: pp. 29-50.
Nara, M., Tasumi, M., Tanokura, M., Hiraoki, T., Yazawa, M. and A. Tsutsumi, (1994). "Infrared studies of interaction between metal ions and Ca2+-binding proteins Marker bands for identifying the types of coordination of the side-chain COO− groups to metal ions in pike parvalbumin (pI= 4.10)." FEBS Letters, 349(1): 84-88. doi:10.1016/0014-5793(94)00645-8.
Neves, L. F. F., Krais, J. J., Van Rite, B. D., Ramesh, R., Resasco, D. E. and R. G. Harrison, (2013). "Targeting single-walled carbon nanotubes for the treatment of breast cancer using photothermal therapy." Nanotechnology, 24(37): 375104. doi:10.1088/0957-4484/24/37/375104.
Ong, S. G., Ming, L. C., Lee, K. S. and K. H. Yuen, (2016). "Influence of the encapsulation efficiency and size of liposome on the oral bioavailability of griseofulvin-loaded liposomes." Pharmaceutics, 8(3): 25. doi:10.3390/pharmaceutics8030025.
Pandey, A. N., Raj, R., Ganesh, N. and S. K. Jain, (2018). "Concanavalin-A conjugated 5-fluorouracil loaded PLGA nanoparticles: A novel approach for effective treatment of colorectal cancer." Research Journal of Pharmacy and Technology, 11(7): 2782-2791. doi:10.5958/0974-360x.2018.00514.0.
Patel, K., Doddapaneni, R., Sekar, V., Chowdhury, N., and M. Singh, (2016). "Combination approach of YSA peptide anchored docetaxel stealth liposomes with oral antifibrotic agent for the treatment of lung cancer." Molecular Pharmaceutics, 13(6): 2049-2058. doi:10.1021/acs.molpharmaceut.6b00187.
Pathak, D. and R. Mallik, (2017). "Lipid - motor interactions: Soap opera or symphony?" Current Opinion in Cell Biology, 44: 79-85. doi:10.1016/j.ceb.2016.09.005.
Patra, J.K., Das, G., Fraceto, L.F., Campos, E.V.R., del Pilar Rodriguez-Torres, M., Acosta-Torres, L.S., Diaz-Torres, L.A., Grillo, R., Swamy, M.K., Sharma, S. and S. Habtemariam, (2018). "Nano based drug delivery systems: recent developments and future prospects." Journal of Nanobiotechnology, 16(1): 71. doi:10.1186/s12951-018-0392-8.
Pignatello, R., Di Guardo, L., Puleo, A. and G. Puglisi, (2005). "Lipophilic conjugates of methotrexate with glucosyl-lipoamino acids: calorimetric study of the interaction with a biomembrane model." Thermochimica Acta, 426(1-2): 163-171. doi:10.1016/j.tca.2004.07.017.
Quinn, P. J. (2004). "Plasma membrane phospholipid asymmetry." In: Quinn, P. J. and V. E. Kagan, (Eds.), Phospholipid Metabolism in Apoptosis, Springer, Boston, MA. 36: 39-60.
Ray, S. and A. Chakrabarti, (2004). "Membrane interaction of erythroid spectrin: surface-density-dependent high-affinity binding to phosphatidylethanolamine." Molecular Membrane Biology, 21(2): 93-100. doi:10.1080/09687680310001625800.
Robinson, T.J. (2014). Box-Behnken Designs. In Wiley StatsRef: Statistics Reference Online (Eds: N. Balakrishnan, T. Colton, B. Everitt, W. Piegorsch, F. Ruggeri and J.L. Teugels). doi:10.1002/9781118445112.stat04101.
Sharma, B. and S.S. Kanwar, (2018). "Phosphatidylserine: A cancer cell targeting biomarker." Seminars in Cancer Biology, 52(Pt 1): 17-25. doi:10.1016/j.semcancer.2017.08.012.
Sikorski, A. F., Hanus-Lorenz, B., Jezierski, A. and A. R. Dluzewski, (2000). "Interaction of membrane skeletal proteins with membrane lipid domain." Acta Biochimica Polonica, 47(3): 565-578.
Silva, R., Ferreira, H., Little, C. and A. Cavaco-Paulo, (2010). "Effect of ultrasound parameters for unilamellar liposome preparation." Ultrasonics Sonochemistry, 17(3): 628-632. doi:10.1016/j.ultsonch.2009.10.010.
Skehan, P., Storeng, R., Scudiero, D., Monks, A., McMahon, J., Vistica, D., Warren, J.T., Bokesch, H., Kenney, S. and M.R. Boyd, (1990). "New colorimetric cytotoxicity assay for anticancer-drug screening." Journal of the National Cancer Institute, 82(13): 1107-1112. doi:10.1093/jnci/82.13.1107.
Soni, V., Kohli, D. V. and S. K. Jain, (2007). "Transferrin coupled liposomes for enhanced brain delivery of doxorubicin." Vascular Disease Prevention, 4(1): 31-38. doi:10.2174/1567270010704010031.
Soni, V., Kohli, D. V. and S. K. Jain, (2008). "Transferrin-conjugated liposomal system for improved delivery of 5-fluorouracil to brain." Journal of Drug Targeting, 16(1): 73-78. doi:10.1080/10611860701725381.
Sou, K. (2011). "Electrostatics of carboxylated anionic vesicles for improving entrapment capacity." Chemistry and Physics of Lipids, 164(3): 211-215. doi:10.1016/j.chemphyslip.2011.01.002.
Spector, A. A. and M. A. Yorek, (1985). "Membrane lipid composition and cellular function." Journal of Lipid Research, 26(9): 1015-1035.
Sugimura, M., Donato, R., Kakkar, V. V. and M. F. Scully, (1994). "Annexin-V as a probe of the contribution of anionic phospholipids to the procoagulant activity of tumor-cell surfaces." Blood Coagulation and Fibrinolysis, 5(3): 365-373.
Tiwari, R., Viswanathan, K., Vyas, S. P. and V. Soni, (2020). "In vitro evaluation of lectinized cisplatin bearing liposomes system." International Journal of Applied Pharmaceutics, 7: 60-64. doi:10.22159/ijap.2020v12i6.39350.
Vichai, V. and K. Kirtikara, (2006). "Sulforhodamine B colorimetric assay for cytotoxicity screening." Nature Protocols, 1(3): 1112-1116. doi:10.1038/nprot.2006.179.
Wang, L., Zhang, M., Zhang, N., Shi, J., Zhang, H., Li, M., Lu, C. and Z. Zhang, (2011). "Synergistic enhancement of cancer therapy using a combination of docetaxel and photothermal ablation induced by single-walled carbon nanotubes." International Journal of Nanomedicine, 6: 2641-2652. doi:10.2147/IJN.S24167.
Winter, P. M., Pearce, J., Chu, Z., McPherson, C. M., Takigiku, R., Lee, J. H. and X. Qi, (2015). "Imaging of brain tumors with paramagnetic vesicles targeted to phosphatidylserine." Journal of Magnetic Resonance Imaging, 41(4): 1079-1087. doi:10.1002/jmri.24654.
Woodbury, D. J., Richardson, E. S., Grigg, A. W., Welling, R. D. and B. H. Knudson, (2006). "Reducing liposome size with ultrasound: bimodal size distributions." Journal of Liposome Research, 16(1): 57-80. doi:10.1080/08982100500528842.
World Health Organisation, WHO (2021). "Cancer." Fact sheets. Retrieved from https://www.who.int/news-room/fact-sheets/detail/cancer [21 September 2021].
Zhang, Y., Huo, M., Zhou, J., Zou, A., Li, W., Yao, C. and S. Xie, (2010). "DDSolver: an add-in program for modeling and comparison of drug dissolution profiles." The AAPS journal, 12(3): 263-271. doi:10.1208/s12248-010-9185-1.
Zhang, Y., Yang, M., Portney, N.G., Cui, D., Budak, G., Ozbay, E., Ozkan, M. and C.S. Ozkan, (2008). "Zeta potential: a surface electrical characteristic to probe the interaction of nanoparticles with normal and cancer human breast epithelial cells." Biomedical Microdevices, 10(2): 321-328. doi:10.1007/s10544-007-9139-2.
Zwaal, R. F. and A. J. Schroit, (1997). "Pathophysiologic implications of membrane phospholipid asymmetry in blood cells." Blood, 89(4): 1121-1132. doi:10.1182/blood.V89.4.1121.
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