Login Register Cart 0
Generic placeholder image

Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Research Article

Hybrid Nanoparticle for Co-delivering Paclitaxel and Dihydroartemisinin to Exhibit Synergic Anticancer Therapeutics

Author(s): Bao Ngoc Tran, Thu Thi Kim Ninh, Thao Thi Do, Phuong Thi Do and Chien Ngoc Nguyen*

Volume 24, Issue 12, 2024

Published on: 06 February, 2024

Page: [1250 - 1261] Pages: 12

DOI: 10.2174/0115680096283208231229103822

Price: $65

Open Access Journals Promotions 2
Abstract

Aim: Anticancer treatment is required to provide effective and safe patient medicines. This research aided in developing and applying nanoparticles (NPs) for cancer treatment.

Background: The poor solubility of paclitaxel (PTX) restricts its therapeutic efficacy because of allergic side effects caused by formulation excipients. To overcome this, PTX was coupled with artemisinin derivatives and loaded into an NP drug delivery system to enhance its effects while addressing its low solubility.

Objectives: This study prepared and characterized a hybrid PLGA-lecithin NP containing dihydroartemisinin (DHA) and PTX for synergic anticancer therapy. A lyophilization study improved the stability of the NP drug formulations.

Methods: Dual PTX- and DHA-loaded PLGA- and lecithin-based NPs were prepared using a single-step solvent evaporation method. The NP suspensions were lyophilized, and the types and ratios of cryoprotectants were investigated. The physicochemical properties of NPs and lyophilized cakes (Lyo-NPs) were characterized. The stability of the Lyo-NPs was investigated at 2-8°C and room conditions. The anticancer effects of the drug combination, NP suspension, and lyophilized powder were analyzed using an in vitro cytotoxicity assay and an in vivo model.

Results: The optimal PTX-DHA loaded PLGA-lecithin-NP was formulated (200 nm, PDI: 0.248 ± 0.003, Zeta potential: -33.60 ± 3.39 mV). Mannitol was selected for lyophilization. Lyo-NPs improved the stability of the NPs (1 year), wherein the physicochemical properties of the NPs were maintained (RDI was close to 1.0). An in-vitro cytotoxicity assay of PTX combined with DHA showed a synergistic anticancer effect (CI <1.0). The suppressive effects of Lyo-NPs on tumor growth in vivo were dose-dependent. While the cocktail of free drugs showed high toxicity (7.5 mg PTX-15 mg DHA/kg) in-vivo, Lyo-NPs showed no statistical differences in hematological and biochemical parameters compared to the control.

Conclusion: Dual-drug-loaded hybrid PLGA-lecithin NP is a potential system to minimize severe side effects while enhancing antitumor efficacy, in which lyophilization is a key process to increase stability.

Keywords: Paclitaxel, synergic therapy, hybrid nanoparticle, anticancer therapy, lyophilization, stability, artemisinin derivatives.

« Previous Next »
Graphical Abstract

[1]
Kalaydina, R.V.; Bajwa, K.; Qorri, B.; DeCarlo, A.; Szewczuk, M.R. Recent advances in “smart” delivery systems for extended drug release in cancer therapy. Int. J. Nanomedicine, 2018, 13, 4727-4745.
[http://dx.doi.org/10.2147/IJN.S168053] [PMID: 30154657]
[2]
Rowinsky, E.K.; Cazenave, L.A.; Donehower, R.C. Taxol: A novel investigational antimicrotubule agent. J. Natl. Cancer Inst., 1990, 82(15), 1247-1259.
[http://dx.doi.org/10.1093/jnci/82.15.1247] [PMID: 1973737]
[3]
Ma, P Paclitaxel nano-delivery systems: A comprehensive review. J. Nanomed. Nanotechnol., 2013, 4(2), 1000164.
[4]
Liebmann, J.; Cook, J.A.; Lipschultz, C.; Teague, D.; Fisher, J.; Mitchell, J.B. The influence of Cremophor EL on the cell cycle effects of paclitaxel (Taxol) in human tumor cell lines. Cancer Chemother. Pharmacol., 1994, 33(4), 331-339.
[http://dx.doi.org/10.1007/BF00685909] [PMID: 7904231]
[5]
Weiss, R.B.; Donehower, R.C.; Wiernik, P.H.; Ohnuma, T.; Gralla, R.J.; Trump, D.L.; Baker, J.R., Jr; Van Echo, D.A.; Von Hoff, D.D.; Leyland-Jones, B. Hypersensitivity reactions from taxol. J. Clin. Oncol., 1990, 8(7), 1263-1268.
[http://dx.doi.org/10.1200/JCO.1990.8.7.1263] [PMID: 1972736]
[6]
Miele, E.; Spinelli, G.P.; Miele, E. Albumin-bound formulation of paclitaxel (Abraxane® ABI-007) in the treatment of breast cancer. Int. J. Nanomedicine, 2009, 4, 99-105.
[7]
Tran, B.N.; Nguyen, H.T.; Kim, J.O.; Yong, C.S.; Nguyen, C.N. Developing combination of artesunate with paclitaxel loaded into poly- D,L -lactic-co-glycolic acid nanoparticle for systemic delivery to exhibit synergic chemotherapeutic response. Drug Dev. Ind. Pharm., 2017, 43(12), 1952-1962.
[http://dx.doi.org/10.1080/03639045.2017.1357729] [PMID: 28724314]
[8]
Tran, B.N.; Nguyen, H.T.; Kim, J.O. Combination of a chemopreventive agent and paclitaxel in CD44-targeted hybrid nanoparticles for breast cancer treatment. Arch. Pharm. Res., 2017, 40(12), 1420-1432.
[http://dx.doi.org/10.1007/s12272-017-0968-0]
[9]
Phung, C.D.; Le, T.G.; Nguyen, V.H. PEGylated-paclitaxel and dihydroartemisinin nanoparticles for simultaneously delivering paclitaxel and dihydroartemisinin to colorectal cancer. Pharm. Res., 2020, 37(7), 129.
[http://dx.doi.org/10.1007/s11095-020-02819-7]
[10]
Jiang, Y.; Zhou, Y.; Zhang, C.Y. Co-delivery of paclitaxel and doxorubicin by ph-responsive prodrug micelles for cancer therapy. Int. J. Nanomedicine, 2020, 15, 3319-3331.
[http://dx.doi.org/10.2147/IJN.S249144]
[11]
Mohamad Saimi, N.I.; Salim, N.; Ahmad, N.; Abdulmalek, E.; Abdul Rahman, M.B. Aerosolized niosome formulation containing gemcitabine and cisplatin for lung cancer treatment: Optimization, characterization and in vitro evaluation. Pharmaceutics, 2021, 13(1), 59.
[http://dx.doi.org/10.3390/pharmaceutics13010059] [PMID: 33466428]
[12]
Mokhtari, R.B.; Homayouni, T.S.; Baluch, N. Combination therapy in combating cancer. Oncotarget, 2017, 8(23), 38022-38043.
[http://dx.doi.org/10.18632/oncotarget.16723]
[13]
Greco, F.; Vicent, MJ Combination therapy: Opportunities and challenges for polymer-drug conjugates as anticancer nanomedicines. Adv. Drug Deliv. Rev., 2009, 61(13), 1203-1213.
[14]
Bishop, J.F.; Dewar, J.; Toner, G.C.; Smith, J.; Tattersall, M.H.N.; Olver, I.N.; Ackland, S.; Kennedy, I.; Goldstein, D.; Gurney, H.; Walpole, E.; Levi, J.; Stephenson, J.; Canetta, R. Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as front-line therapy in untreated metastatic breast cancer. J. Clin. Oncol., 1999, 17(8), 2355-2364.
[http://dx.doi.org/10.1200/JCO.1999.17.8.2355] [PMID: 10561297]
[15]
Danhier, F.; Lecouturier, N.; Vroman, B.; Jérôme, C.; Marchand-Brynaert, J.; Feron, O.; Préat, V. Paclitaxel-loaded PEGylated PLGA-based nanoparticles: In vitro and in vivo evaluation. J. Control. Release, 2009, 133(1), 11-17.
[http://dx.doi.org/10.1016/j.jconrel.2008.09.086] [PMID: 18950666]
[16]
Fonseca, C.; Simões, S.; Gaspar, R. Paclitaxel-loaded PLGA nanoparticles: Preparation, physicochemical characterization and in vitro anti-tumoral activity. J. Control. Release, 2002, 83(2), 273-286.
[http://dx.doi.org/10.1016/S0168-3659(02)00212-2] [PMID: 12363453]
[17]
Nguyen, H.T.; Tran, T.H.; Kim, J.O.; Yong, C.S.; Nguyen, C.N. Enhancing the in vitro anti-cancer efficacy of artesunate by loading into poly-d,l-lactide-co-glycolide (PLGA) nanoparticles. Arch. Pharm. Res., 2015, 38(5), 716-724.
[http://dx.doi.org/10.1007/s12272-014-0424-3] [PMID: 24968925]
[18]
Chu, X-Y.; Huang, W.; Wang, Y-L Improving antitumor outcomes for palliative intratumoral injection therapy through lecithin- chitosan nanoparticles loading paclitaxel- cholesterol complex. Int. J. Nanomed., 2019, 14, 689-705.
[19]
Zolnik, B.S.; Burgess, DJ Effect of acidic pH on PLGA microsphere degradation and release. J. Control. Release, 2007, 122(3), 338-344.
[http://dx.doi.org/10.1016/j.jconrel.2007.05.034]
[20]
Yoo, J.Y.; Kim, J.M.; Seo, K.S.; Jeong, Y.K.; Lee, H.B.; Khang, G. Characterization of degradation behavior for PLGA in various pH condition by simple liquid chromatography method. Biomed. Mater. Eng., 2005, 15(4), 279-288.
[PMID: 16010036]
[21]
Comas, DI; Wagner, JR; Tomás, MC Creaming stability of oil in water (O/W) emulsions: Influence of pH on soybean protein–lecithin interaction. 2006, 20(7), 990-996.
[22]
Tran, T.B.; Tran, T.H.; Vu, YH pH-responsive nanocarriers for combined chemotherapies: A new approach with old materials. Cellulose, 2021, 28(6), 3423-3433.
[23]
Ball, R.L.; Bajaj, P. Achieving long-term stability of lipid nanoparticles: Examining the effect of pH, temperature, and lyophilization. Int. J. Nanomedicine, 2017, 12, 305-315.
[24]
Patel, S.M.; Nail, S.L.; Pikal, M.J. Lyophilized drug product cake appearance: What is acceptable? J. Pharm. Sci., 2017, 106(7), 1706-1721.
[http://dx.doi.org/10.1016/j.xphs.2017.03.014]
[25]
Kasper, J.C.; Winter, G.; Friess, W. Recent advances and further challenges in lyophilization. Eur. J. Pharm. Biopharm., 2013, 85(2), 162-169.
[http://dx.doi.org/10.1016/j.ejpb.2013.05.019]
[26]
Holzer, M.; Vogel, V.; Mäntele, W.; Schwartz, D.; Haase, W.; Langer, K. Physico-chemical characterisation of PLGA nanoparticles after freeze-drying and storage. Eur. J. Pharm. Biopharm., 2009, 72(2), 428-437.
[http://dx.doi.org/10.1016/j.ejpb.2009.02.002] [PMID: 19462479]
[27]
Ho, H.N.; Laidmäe, I.; Kogermann, K.; Lust, A.; Meos, A.; Nguyen, C.N.; Heinämäki, J. Development of electrosprayed artesunate-loaded core-shell nanoparticles. Drug Dev. Ind. Pharm., 2017, 43(7), 1134-1142.
[http://dx.doi.org/10.1080/03639045.2017.1300163] [PMID: 28277847]
[28]
Monks, A.; Scudiero, D.; Skehan, P.; Shoemaker, R.; Paull, K.; Vistica, D.; Hose, C.; Langley, J.; Cronise, P.; Vaigro-Wolff, A.; Gray-Goodrich, M.; Campbell, H.; Mayo, J.; Boyd, M. Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines. J. Natl. Cancer Inst., 1991, 83(11), 757-766.
[http://dx.doi.org/10.1093/jnci/83.11.757] [PMID: 2041050]
[29]
Ninh, T.T.K.; Tran, T.H.; Huang, C-Y.F. Application of computational screening tools and nanotechnology for enhanced drug synergism in cancer therapy. Curr. Drug Deliv., 2023, 20(7), 1015-1029.
[http://dx.doi.org/10.2174/1567201819666220426092538]
[30]
Wang, Y.; Chen, J.; Yang, Y. Oil-water partition coefficient preparation and detection in the dihydroartemisinin self-emulsifying drug delivery system. BMC Biotechnol., 2022, 22(1), 16.
[http://dx.doi.org/10.1186/s12896-022-00746-6]
[31]
Ansari, M.T.; Batty, K.T.; Iqbal, I. Improving the solubility and bioavailability of dihydroartemisinin by solid dispersions and inclusion complexes. Arch. Pharm. Res., 2011, 34(5), 757-765.
[http://dx.doi.org/10.1007/s12272-011-0509-1]
[32]
Wishart, D.S.; Feunang, Y.D.; Guo, A.C.; Lo, E.J.; Marcu, A.; Grant, J.R.; Sajed, T.; Johnson, D.; Li, C.; Sayeeda, Z.; Assempour, N.; Iynkkaran, I.; Liu, Y.; Maciejewski, A.; Gale, N.; Wilson, A.; Chin, L.; Cummings, R.; Le, D.; Pon, A.; Knox, C.; Wilson, M. DrugBank 5.0: A major update to the DrugBank database for 2018. Nucleic Acids Res., 2018, 46(D1), D1074-D1082.
[http://dx.doi.org/10.1093/nar/gkx1037] [PMID: 29126136]
[33]
Liu, J.; Huang, Y.; Kumar, A pH-Sensitive nano-systems for drug delivery in cancer therapy. Biotechnol. Adv., 2014, 32(4), 693-710.
[34]
Cao, Z.; Li, W.; Liu, R pH-and enzyme-triggered drug release as an important process in the design of anti-tumor drug delivery systems. Biomed. Pharmacother., 2019, 118, 109340.
[35]
Circioban, D.; Ledeti, A.; Vlase, G. Thermal stability and kinetic degradation study for dihydroartemisinin. J. Therm. Anal. Calorim., 2020, 142(10), 6.
[http://dx.doi.org/10.1007/s10973-020-09902-6]
[36]
Wang, L.; Wang, Y.; Wang, X.; Sun, L.; Zhou, Z.; Lu, J.; Zheng, Y. Encapsulation of low lipophilic and slightly water-soluble dihydroartemisinin in PLGA nanoparticles with phospholipid to enhance encapsulation efficiency and in vitro bioactivity. J. Microencapsul., 2016, 33(1), 43-52.
[http://dx.doi.org/10.3109/02652048.2015.1114042] [PMID: 26626402]
[37]
Chen, Y.; Chin, B.W.; Bieber, M.M.; Tan, X.; Teng, N.N. Abstract 470: Artemisinin derivatives synergize with paclitaxel by targeting FOXM1 through Raf/MEK/MAPK signaling pathway in ovarian cancer. Cancer Res., 2014, 74(19_Supplement), 470.
[http://dx.doi.org/10.1158/1538-7445.AM2014-470]
[38]
Liu, J.; Chen, Q.; Feng, L. Nanomedicine for tumor microenvironment modulation and cancer treatment enhancement. Nano Today, 2018, 21.
[http://dx.doi.org/10.1016/j.nantod.2018.06.008]
[39]
Parolini, I.; Federici, C.; Raggi, C Microenvironmental pH is a key factor for exosome traffic in tumor cells. J. Biol. Chem., 2009, 284(49), 34211-34222.
[http://dx.doi.org/10.1074/jbc.M109.041152]
[40]
Ashton, JC Drug combination studies and their synergy quantification using the Chou–Talalay method., 2015, 75(11), 2400.

Rights & Permissions Print Cite
Article Metrics
33
1
Wayfinder Image
Open Access Journals Promotions
© 2024 Bentham Science Publishers | Privacy Policy