Generic placeholder image

Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

Combretastatin A4-loaded Poly (Lactic-co-glycolic Acid)/Soybean Lecithin Nanoparticles with Enhanced Drug Dissolution Rate and Antiproliferation Activity

Author(s): Yue Cao, Atef Mohammed Qasem Ahmed, Huan-Huan Du, Wei Sun, Xiaojuan Lu, Zhao Xu, Jing Tao* and Qing-Ri Cao*

Volume 19, Issue 9, 2022

Published on: 28 March, 2022

Page: [918 - 927] Pages: 10

DOI: 10.2174/1567201819666220209093443

Price: $65

Abstract

Objective: This study aimed to prepare combretastatin A4 (CA4)-loaded nanoparticles (CA4 NPs) using poly(lactic-co-glycolic acid) (PLGA) and soybean lecithin (Lipoid S100) as carriers, and further evaluate the physicochemical properties and cytotoxicities of CA4 NPs against cancer cells.

Methods: CA4 NPs were prepared using a solvent evaporation technique. The effects of formulations on CA4 NPs were investigated in terms of particle size, zeta potential, encapsulation efficacy, and drug loading. The physicochemical properties of CA4 NPs were characterized using transmission electron microscopy, X-ray powder diffraction, differential scanning calorimetry, and Fourier transform infrared spectra. The drug release from CA4NPs was performed using a dialysis method. In addition, the cytotoxicity of CA4NPs against human alveolar basal epithelial (A549) cells was also evaluated.

Results: CA4 NPs prepared with a low organic/water phase ratio (1:20) and high drug/PLGA mass ratio (1:2.5) exhibited a uniform hydrodynamic particle size of 142 nm, the zeta potential of -1.66 mV, and encapsulation efficacy and drug loading of 92.1% and 28.3%, respectively. CA4 NPs showed a significantly higher release rate than pure CA4 in pH 7.4 phosphate-buffered solution with 0.5% Tween 80. It was found that the drug molecules could change from the crystal state to an amorphous form when loaded into the PLGA/Lipoid S100 matrix, and some molecular interactions could also occur between the drug and PLGA. Importantly, CA4 NPs showed a remarkably higher antiproliferation activity against A549 cancer cells compared to pure CA4.

Conclusion: These results suggested the promising potential of PLGA/Lipoid S100 nanoparticles as the drug delivery system of CA4 for effective cancer therapy.

Keywords: Combretastatin A4, nanoparticles, PLGA/Lipoid S100, dissolution, antiproliferation activity, physicochemical characteristics, cytotoxicity.

Graphical Abstract

[1]
Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell, 2011, 144(5), 646-674.
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[2]
Carmeliet, P.; Jain, R.K. Angiogenesis in cancer and other diseases. Nature, 2000, 407(6801), 249-257.
[http://dx.doi.org/10.1038/35025220] [PMID: 11001068]
[3]
Pedrosa, L.; Esposito, F.; Thomson, T.M.; Maurel, J. The tumor microenvironment in colorectal cancer therapy. Cancers (Basel), 2019, 11(8), E1172.
[http://dx.doi.org/10.3390/cancers11081172] [PMID: 31416205]
[4]
Shojaei, F.; Ferrara, N. Antiangiogenesis to treat cancer and intraocular neovascular disorders. Lab. Invest., 2007, 87(3), 227-230.
[http://dx.doi.org/10.1038/labinvest.3700526] [PMID: 17259997]
[5]
Kuczynski, E.A.; Vermeulen, P.B.; Pezzella, F.; Kerbel, R.S.; Reynolds, A.R. Vessel co-option in cancer. Nat. Rev. Clin. Oncol., 2019, 16(8), 469-493.
[http://dx.doi.org/10.1038/s41571-019-0181-9] [PMID: 30816337]
[6]
Gavalas, N.G.; Liontos, M.; Trachana, S.P.; Bagratuni, T.; Arapinis, C.; Liacos, C.; Dimopoulos, M.A.; Bamias, A. Angiogenesis-related pathways in the pathogenesis of ovarian cancer. Int. J. Mol. Sci., 2013, 14(8), 15885-15909.
[http://dx.doi.org/10.3390/ijms140815885] [PMID: 23903048]
[7]
Folkman, J. Tumor angiogenesis: therapeutic implications. N. Engl. J. Med., 1971, 285(21), 1182-1186.
[http://dx.doi.org/10.1056/NEJM197111182852108] [PMID: 4938153]
[8]
Quillien, V.; Carpentier, A.F.; Gey, A.; Avril, T.; Tartour, E.; Sejalon, F.; Campillo-Gimenez, B.; Vauleon, E. Absolute numbers of regulatory T cells and neutrophils in corticosteroid-free patients are predictive for response to bevacizumab in recurrent glioblastoma patients. Cancer Immunol. Immunother., 2019, 68(6), 871-882.
[http://dx.doi.org/10.1007/s00262-019-02317-9] [PMID: 30830269]
[9]
Rini, B.I.; Powles, T.; Atkins, M.B.; Escudier, B.; McDermott, D.F.; Suarez, C.; Bracarda, S.; Stadler, W.M.; Donskov, F.; Lee, J.L.; Hawkins, R.; Ravaud, A.; Alekseev, B.; Staehler, M.; Uemura, M.; De Giorgi, U.; Mellado, B.; Porta, C.; Melichar, B.; Gurney, H.; Bedke, J.; Choueiri, T.K.; Parnis, F.; Khaznadar, T.; Thobhani, A.; Li, S.; Piault-Louis, E.; Frantz, G.; Huseni, M.; Schiff, C.; Green, M.C.; Motzer, R.J.; Group, I.M.S. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): A multicentre, open-label, phase 3, randomised controlled trial. Lancet, 2019, 393(10189), 2404-2415.
[http://dx.doi.org/10.1016/S0140-6736(19)30723-8] [PMID: 31079938]
[10]
Su, J.; Laursen, B.E.; Eskildsen-Helmond, Y.; Horsman, M.R.; Simonsen, U. The vascular-disrupting agent, combretastatin-A4-phosphate, enhances neurogenic vasoconstriction in rat small arteries. Eur. J. Pharmacol., 2012, 695(1-3), 104-111.
[http://dx.doi.org/10.1016/j.ejphar.2012.08.023] [PMID: 22981665]
[11]
Banerjee, S.; Hwang, D.J.; Li, W.; Miller, D.D. Current advances of tubulin inhibitors in nanoparticle drug delivery and vascular disrup-tion/angiogenesis. Molecules, 2016, 21(11), E1468.
[http://dx.doi.org/10.3390/molecules21111468] [PMID: 27827858]
[12]
Nik, M.E.; Momtazi-Borojeni, A.A.; Zamani, P.; Navashenaq, J.G.; Iranshahi, M.; Jaafari, M.R.; Malaekeh-Nikouei, B. Targeted-nanoliposomal combretastatin A-4 (CA-4) as an efficient antivascular candidate in the metastatic cancer treatment. J. Cell. Physiol., 2019.
[http://dx.doi.org/10.1002/jcp.28230] [PMID: 30697744]
[13]
West, C.M.; Price, P. Combretastatin A4 phosphate. Anticancer Drugs, 2004, 15(3), 179-187.
[http://dx.doi.org/10.1097/00001813-200403000-00001] [PMID: 15014350]
[14]
Tozer, G.M.; Kanthou, C.; Baguley, B.C. Disrupting tumour blood vessels. Nat. Rev. Cancer, 2005, 5(6), 423-435.
[http://dx.doi.org/10.1038/nrc1628] [PMID: 15928673]
[15]
Ibrahim, M.A.; Do, D.V.; Sepah, Y.J.; Shah, S.M.; Van Anden, E.; Hafiz, G.; Donahue, J.K.; Rivers, R.; Balkissoon, J.; Handa, J.T.; Campochiaro, P.A.; Nguyen, Q.D. Vascular disrupting agent for neovascular age related macular degeneration: a pilot study of the safety and efficacy of intravenous combretastatin A-4 phosphate. BMC Pharmacol. Toxicol., 2013, 14, 7.
[http://dx.doi.org/10.1186/2050-6511-14-7] [PMID: 23316779]
[16]
Ng, Q.S.; Mandeville, H.; Goh, V.; Alonzi, R.; Milner, J.; Carnell, D.; Meer, K.; Padhani, A.R.; Saunders, M.I.; Hoskin, P.J. Phase Ib trial of radiotherapy in combination with combretastatin-A4-phosphate in patients with non-small-cell lung cancer, prostate adenocarcinoma, and squamous cell carcinoma of the head and neck. Ann. Oncol., 2012, 23(1), 231-237.
[http://dx.doi.org/10.1093/annonc/mdr332] [PMID: 21765046]
[17]
Dowlati, A.; Robertson, K.; Cooney, M.; Petros, W.P.; Stratford, M.; Jesberger, J.; Rafie, N.; Overmoyer, B.; Makkar, V.; Stambler, B.; Taylor, A.; Waas, J.; Lewin, J.S.; McCrae, K.R.; Remick, S.C. A phase I pharmacokinetic and translational study of the novel vascular targeting agent combretastatin A-4 phosphate on a single-dose intravenous schedule in patients with advanced cancer. Cancer Res., 2002, 62(12), 3408-3416.
[PMID: 12067983]
[18]
Rustin, G.J.; Galbraith, S.M.; Anderson, H.; Stratford, M.; Folkes, L.K.; Sena, L.; Gumbrell, L.; Price, P.M. Phase I clinical trial of weekly combretastatin A-4 phosphate: clinical and pharmacokinetic results. J. Clin. Oncol., 2003, 21(15), 2815-2822.
[http://dx.doi.org/10.1200/JCO.2003.05.185] [PMID: 12807934]
[19]
Young, S.L.; Chaplin, D.J. Combretastatin A4 phosphate: background and current clinical status. Expert Opin. Investig. Drugs, 2004, 13(9), 1171-1182.
[http://dx.doi.org/10.1517/13543784.13.9.1171] [PMID: 15330748]
[20]
Cooney, M.M.; Radivoyevitch, T.; Dowlati, A.; Overmoyer, B.; Levitan, N.; Robertson, K.; Levine, S.L.; DeCaro, K.; Buchter, C.; Taylor, A.; Stambler, B.S.; Remick, S.C. Cardiovascular safety profile of combretastatin A-4 phosphate in a single-dose phase I study in patients with advanced cancer. Clin. Cancer Res., 2004, 10(1 Pt 1), 96-100.
[http://dx.doi.org/10.1158/1078-0432.CCR-0364-3] [PMID: 14734457]
[21]
He, X.; Li, S.; Huang, H.; Li, Z.; Chen, L.; Ye, S.; Huang, J.; Zhan, J.; Lin, T. A pharmacokinetic and safety study of single dose intravenous combretastatin A-4 phosphate in Chinese patients with refractory solid tumours. Br. J. Clin. Pharmacol., 2011, 71(6), 860-870.
[http://dx.doi.org/10.1111/j.1365-2125.2011.03928.x] [PMID: 21276042]
[22]
Grosios, K.; Holwell, S.E.; McGown, A.T.; Pettit, G.R.; Bibby, M.C. In vivo and in vitro evaluation of combretastatin A-4 and its sodium phosphate prodrug. Br. J. Cancer, 1999, 81(8), 1318-1327.
[http://dx.doi.org/10.1038/sj.bjc.6692174] [PMID: 10604728]
[23]
Yang, M.; Li, J.; Gu, P.; Fan, X. The application of nanoparticles in cancer immunotherapy: Targeting tumor microenvironment. Bioact. Mater., 2020, 6(7), 1973-1987.
[http://dx.doi.org/10.1016/j.bioactmat.2020.12.010] [PMID: 33426371]
[24]
Zhao, N.; Woodle, M.C.; Mixson, A.J. Advances in delivery systems for doxorubicin. J. Nanomed. Nanotechnol., 2018, 9(5), 519.
[http://dx.doi.org/10.4172/2157-7439.1000519] [PMID: 30613436]
[25]
Golla, K.; Cherukuvada, B.; Ahmed, F.; Kondapi, A.K. Efficacy, safety and anticancer activity of protein nanoparticle-based delivery of dox-orubicin through intravenous administration in rats. PLoS One, 2012, 7(12), e51960.
[http://dx.doi.org/10.1371/journal.pone.0051960] [PMID: 23284832]
[26]
Qi, F.; Wu, J.; Hao, D.; Yang, T.; Ren, Y.; Ma, G.; Su, Z. Comparative studies on the influences of primary emulsion preparation on proper-ties of uniform-sized exenatide-loaded PLGA microspheres. Pharm. Res., 2014, 31(6), 1566-1574.
[http://dx.doi.org/10.1007/s11095-013-1262-6] [PMID: 24398695]
[27]
Ding, D.; Zhu, Q. Recent advances of PLGA micro/nanoparticles for the delivery of biomacromolecular therapeutics. Mater. Sci. Eng. C, 2018, 92, 1041-1060.
[http://dx.doi.org/10.1016/j.msec.2017.12.036] [PMID: 30184728]
[28]
Silva, A.L.; Soema, P.C.; Slütter, B.; Ossendorp, F.; Jiskoot, W. PLGA particulate delivery systems for subunit vaccines: Linking particle properties to immunogenicity. Hum. Vaccin. Immunother., 2016, 12(4), 1056-1069.
[http://dx.doi.org/10.1080/21645515.2015.1117714] [PMID: 26752261]
[29]
Ortega-Oller, I.; Padial-Molina, M.; Galindo-Moreno, P.; O’Valle, F.; Jódar-Reyes, A.B.; Peula-García, J.M. Bone regeneration from PLGA micro-nanoparticles. BioMed Res. Int., 2015, 2015, 415289.
[http://dx.doi.org/10.1155/2015/415289] [PMID: 26509156]
[30]
Wang, Y.; Chen, H.; Liu, Y.; Wu, J.; Zhou, P.; Wang, Y.; Li, R.; Yang, X.; Zhang, N. pH-sensitive pullulan-based nanoparticle carrier of methotrexate and combretastatin A4 for the combination therapy against hepatocellular carcinoma. Biomaterials, 2013, 34(29), 7181-7190.
[http://dx.doi.org/10.1016/j.biomaterials.2013.05.081] [PMID: 23791500]
[31]
Xu, J.; Ganesh, S.; Amiji, M. Non-condensing polymeric nanoparticles for targeted gene and siRNA delivery. Int. J. Pharm., 2012, 427(1), 21-34.
[http://dx.doi.org/10.1016/j.ijpharm.2011.05.036] [PMID: 21621597]
[32]
Prabha, S.; Zhou, W.Z.; Panyam, J.; Labhasetwar, V. Size-dependency of nanoparticle-mediated gene transfection: studies with fractionated nanoparticles. Int. J. Pharm., 2002, 244(1-2), 105-115.
[http://dx.doi.org/10.1016/S0378-5173(02)00315-0] [PMID: 12204570]
[33]
Bhalekar, M.R.; Pokharkar, V.; Madgulkar, A.; Patil, N.; Patil, N. Preparation and evaluation of miconazole nitrate-loaded solid lipid nanopar-ticles for topical delivery. AAPS PharmSciTech, 2009, 10(1), 289-296.
[http://dx.doi.org/10.1208/s12249-009-9199-0] [PMID: 19294517]
[34]
Xu, W.J.; Xie, H.J.; Cao, Q.R.; Shi, L.L.; Cao, Y.; Zhu, X.Y.; Cui, J.H. Enhanced dissolution and oral bioavailability of valsartan solid disper-sions prepared by a freeze-drying technique using hydrophilic polymers. Drug Deliv., 2016, 23(1), 41-48.
[http://dx.doi.org/10.3109/10717544.2014.903012] [PMID: 24735247]
[35]
Cao, Q.R.; Liu, Y.; Xu, W.J.; Lee, B.J.; Yang, M.; Cui, J.H. Enhanced oral bioavailability of novel mucoadhesive pellets containing valsartan prepared by a dry powder-coating technique. Int. J. Pharm., 2012, 434(1-2), 325-333.
[http://dx.doi.org/10.1016/j.ijpharm.2012.05.076] [PMID: 22688251]
[36]
Yu, M.; Xu, L.; Tian, F.; Su, Q.; Zheng, N.; Yang, Y.; Wang, J.; Wang, A.; Zhu, C.; Guo, S.; Zhang, X.; Gan, Y.; Shi, X.; Gao, H. Rapid transport of deformation-tuned nanoparticles across biological hydrogels and cellular barriers. Nat. Commun., 2018, 9(1), 2607.
[http://dx.doi.org/10.1038/s41467-018-05061-3] [PMID: 29973592]
[37]
Cao, Y.; Huang, H.Y.; Chen, L.Q.; Du, H.H.; Cui, J.H.; Zhang, L.W.; Lee, B.J.; Cao, Q.R. Enhanced lysosomal escape of pH-responsive poly-ethylenimine-betaine functionalized carbon nanotube for the codelivery of survivin small interfering RNA and doxorubicin. ACS Appl. Mater. Interfaces, 2019, 11(10), 9763-9776.
[http://dx.doi.org/10.1021/acsami.8b20810] [PMID: 30776886]
[38]
Li, B.; Zhang, X.X.; Huang, H.Y.; Chen, L.Q.; Cui, J.H.; Liu, Y.; Jin, H.; Lee, B.J.; Cao, Q.R. Effective deactivation of A549 tumor cells in vitro and in vivo by RGD-decorated chitosan-functionalized single-walled carbon nanotube loading docetaxel. Int. J. Pharm., 2018, 543(1-2), 8-20.
[http://dx.doi.org/10.1016/j.ijpharm.2018.03.017] [PMID: 29535039]
[39]
Shi, L.L.; Xie, H.; Lu, J.; Cao, Y.; Liu, J.Y.; Zhang, X.X.; Zhang, H.; Cui, J.H.; Cao, Q.R. Positively charged surface-modified solid lipid na-noparticles promote the intestinal transport of docetaxel through multifunctional mechanisms in rats. Mol. Pharm., 2016, 13(8), 2667-2676.
[http://dx.doi.org/10.1021/acs.molpharmaceut.6b00226] [PMID: 27379550]
[40]
Shi, L.L.; Cao, Y.; Zhu, X.Y.; Cui, J.H.; Cao, Q.R. Optimization of process variables of zanamivir-loaded solid lipid nanoparticles and the prediction of their cellular transport in Caco-2 cell model. Int. J. Pharm., 2015, 478(1), 60-69.
[http://dx.doi.org/10.1016/j.ijpharm.2014.11.017] [PMID: 25448568]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy