Abstract
Cisplatin, a platinum-based drug, is widely used in cancer treatment but is associated with significant side effects; new treatment delivery methods must be developed which enhance treatment efficiency while decreasing the sequelae of chemotherapy. The aim of this study was to develop novel liposomal nano-particles (NPs) loaded with two drugs including cisplatin and glycyrrhizic acid. This study hypothesized that introducing glycyrrhizic acid, as an adjuvant treatment, and cisplatin, as a chemotherapeutic agent, into a co-delivery system can enhance the therapeutic effect. In this study, the synthetic method and specifications of NPs were evaluated. After surface modification by polyethylene glycol (PEG), the size and the zeta potential of NPs were reported as 81.6 nm and − 30.7 mV, respectively. DLD-1 and LIM-2405 human colon cancer cell lines were then applied to evaluate the cytotoxicity of NPs using an MTT assay. The results revealed that IC50 for DLD-1, as a resistant cell line to cisplatin, decreased by 48% on co-delivery system treatment. Furthermore, to determine the proliferative potential of cell lines and DNA damage on cancerous cells after treatment by NPs and cisplatin in free form, the cell proliferation assay and immunocytochemistry method were performed. The results showed that a co-delivery system caused more than 43% DNA damage to cancerous cells compared with the free form of cisplatin. The finding of this study demonstrates that the co-delivery system has a significant anti-cancer efficiency compared with the free form of cisplatin. To conclude, the results of this study demonstrate a possible application of glycyrrhizic acid as an adjuvant treatment for cisplatin on co-delivery systems.
Graphical abstract
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Alavi SE, Muflih Al Harthi S, Ebrahimi Shahmabadi H, Akbarzadeh A (2019) Cisplatin-loaded polybutylcyanoacrylate nanoparticles with improved properties as an anticancer agent. Int J Mol Sci 20(7):1531. https://doi.org/10.3390/ijms20071531
Andrieux K, Couvreur P (2009) Polyalkylcyanoacrylate nanoparticles for delivery of drugs across the blood–brain barrier. Wiley Interdisciplinary Reviews 1(5):463–474. https://doi.org/10.1002/wnan.5
Arjumand W, Sultana S (2011) Glycyrrhizic acid: a phytochemical with a protective role against cisplatin-induced genotoxicity and nephrotoxicity. Life Sci 89(13):422–429. https://doi.org/10.1016/j.lfs.2011.06.016
Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F (2017) Global patterns and trends in colorectal cancer incidence and mortality. Gut 66(4):683–691. https://doi.org/10.1136/gutjnl-2015-310912
Binefa G, Rodríguez-Moranta F, Teule A, Medina-Hayas M (2014) Colorectal cancer: from prevention to personalized medicine. World J Gastroenterol 20(22):6786–6808. https://doi.org/10.3748/wjg.v20.i22.6786
Chau I, Cunningham D (2002) Chemotherapy in colorectal cancer: new options and new challenges. Br Med Bull 64(1):159–180. https://doi.org/10.1093/bmb/64.1.159
Cooper ER (2010) Nanoparticles: a personal experience for formulating poorly water soluble drugs. J Control Release 141(3):300–302. https://doi.org/10.1016/j.jconrel.2009.10.006
Cosco D, Paolino D, Muzzalupo R, Celia C, Citraro R, Caponio D, Picci N, Fresta M (2009) Novel PEG-coated niosomes based on bola-surfactant as drug carriers for 5-fluorouracil. Biomed Microdevices 11(5):1115–1125. https://doi.org/10.1007/s10544-009-9328-2
Curreli F, Friedman-Kien AE, Flore O (2005) Glycyrrhizic acid alters Kaposi sarcoma-associated herpesvirus latency, triggering p53-mediated apoptosis in transformed B lymphocytes. J Clin Invest 115(3):642–652. https://doi.org/10.1172/jci23334
Davidson S, Haslett C (2002) Davidson’s principles and practice of medicine. Churchill Livingstone, Edinburgh
Ebrahimifar M, Nili-Ahmadabadi A, Akbarzadeh A, Shahemabadi HE, Hasanzadegan M, Moradi-Sardareh H, Madadizadeh H, Rezaee-diyan J (2017a) Preparation, characterization and cytotoxic effects of pegylated nanoliposomal containing carboplatin on ovarian cancer cell lines. Indian J Clin Biochem 32(2):230–234. https://doi.org/10.1007/s12291-016-0596-3
Ebrahimifar M, Hasanzadegan Roudsari M, Kazemi SM, Ebrahimi Shahmabadi H, Kanaani L, Alavi SA, Izadi Vasfi M (2017b) Enhancing effects of curcumin on cytotoxicity of paclitaxel, methotrexate and vincristine in gastric cancer cells. Asian Pac J Cancer Prev 18(1):65–68. https://doi.org/10.22034/apjcp.2017.18.1.65
Farooq MA, Aquib M, Khan DH, Ghayas S, Ahsan A, Ijaz M, Banerjee P, Khan MA, Ahmad MM, Wang B (2019) Nanocarrier-mediated co-delivery systems for lung cancer therapy: recent developments and prospects. Environ Chem Lett 17(4):1565–1583. https://doi.org/10.1007/s10311-019-00897-7
Fotopoulou C (2014) Limitations to the use of carboplatin-based therapy in advanced ovarian cancer. Eur J Cancer Suppl 12(2):13–16. https://doi.org/10.1016/S1359-6349(15)70005-4
Fumoto S, Nishida K (2020) Co-delivery systems of multiple drugs using nanotechnology for future cancer therapy. Chem Pharm Bull 68(7):603–612. https://doi.org/10.1248/cpb.c20-00008
Hamelers IHL, van Loenen E, Staffhorst RWHM, de Kruijff B, de Kroon AIPM (2006) Carboplatin nanocapsules: a highly cytotoxic, phospholipid-based formulation of carboplatin. Mol Cancer Ther 5(8):2007–2012. https://doi.org/10.1158/1535-7163.mct-06-0089
Hassanzadeganroudsari M, Apostolopoulos V, Nurgali K (2018) Development and characterization of targeted nanoparticles loaded with oxaliplatin for colorectal cancer treatment. J Nanomed Nanotechnol:9. https://doi.org/10.4172/2157-7439-C5-080
Hassanzadeganroudsari M, Heydarinasab A, Soltani M, Chen P, Akbarzadeh Khiyavi A (2019a) Enhancing anti-cancer efficacy of carboplatin by PEGylated poly (butyl cyanoacrylate) nano-particles. J Drug Deliv Sci Technol 54:101218. https://doi.org/10.1016/j.jddst.2019.101218
Hassanzadeganroudsari M, Heydarinasab A, Soltani M, Chen P, Akbarzadehkhiyavi A (2019b) Enhancing anti-cancer efficacy of carboplatin by PEGylated poly (butyl cyanoacrylate) nano-particles. J Drug Deliv Sci Technol:101218. https://doi.org/10.1016/j.jddst.2019.101218
Hassanzadeganroudsari M, Heydarinasab A, Akbarzadeh Khiyavi A, Chen P, Soltani M (2019c) In vitro investigation of anticancer efficacy of carboplatin-loaded PEGylated nanoliposome particles on brain cancer cell lines. J Nanopart Res 21(6):124. https://doi.org/10.1007/s11051-019-4562-x
Hassanzadeganroudsari M, Soltani M, Heydarinasab A, Nakhjiri AT, Hossain MDK, Khiyavi AA (2020) Mathematical modeling and simulation of molecular mass transfer across blood brain barrier in brain capillary. J Mol Liq 310:113254. https://doi.org/10.1016/j.molliq.2020.113254
Honary S, Zahir F (2013) Effect of zeta potential on the properties of nano-drug delivery systems - a review (part 1). 12. https://doi.org/10.4314/tjpr.v12i2.19
Kawai F (2002) Microbial degradation of polyethers. Appl Microbiol Biotechnol 58(1):30–38. https://doi.org/10.1007/s00253-001-0850-2
Knop K, Hoogenboom R, Fischer D, Schubert US (2010) Poly (ethylene glycol) in drug delivery: pros and cons as well as potential alternatives. Angew Chem Int Ed 49(36):6288–6308. https://doi.org/10.1002/anie.200902672
Kokotis P, Schmelz M, Kostouros E, Karandreas N, Dimopoulos M-A (2016) Oxaliplatin-induced neuropathy: a long-term clinical and neurophysiologic follow-up study. Clin Colorectal Cancer 15(3):e133–e140. https://doi.org/10.1016/j.clcc.2016.02.009
Lee BK, Yun YH, Park K (2015) Smart nanoparticles for drug delivery: boundaries and opportunities. Chem Eng Sci 125:158–164. https://doi.org/10.1016/j.ces.2014.06.042
Li M, Du C, Guo N, Teng Y, Meng X, Sun H, Li S, Yu P, Galons H (2019) Composition design and medical application of liposomes. Eur J Med Chem 164:640–653. https://doi.org/10.1016/j.ejmech.2019.01.007
Mofidian R, Barati A, Jahanshahi M, Shahavi MH (2019) Optimization on thermal treatment synthesis of lactoferrin nanoparticles via Taguchi design method. SN Appl Sci 1(11):1339. https://doi.org/10.1007/s42452-019-1353-z
Nurgali K, Jagoe RT, Abalo R (2018) Editorial: adverse effects of cancer chemotherapy: anything new to improve tolerance and reduce sequelae? Front Pharmacol 9:245
Ochi MM, Amoabediny G, Rezayat SM, Akbarzadeh A, Ebrahimi B (2016) In vitro co-delivery evaluation of novel pegylated nano-liposomal herbal drugs of silibinin and glycyrrhizic acid (nano-phytosome) to hepatocellular carcinoma cells. Cell J 18(2):135–148. https://doi.org/10.22074/cellj.2016.4308
Pompei R, Flore O, Marccialis MA, Pani A, Loddo B (1979) Glycyrrhizic acid inhibits virus growth and inactivates virus particles. Nature 281(5733):689–690. https://doi.org/10.1038/281689a0
Salahshoori I, Nasirian D, Rashidi N, Hossain MK, Hatami A, Hassanzadeganroudsari M (2020) The effect of silica nanoparticles on polysulfone–polyethylene glycol (PSF/PEG) composite membrane on gas separation and rheological properties of nanocomposites. Polym Bull. https://doi.org/10.1007/s00289-020-03255-8
Shahzad MMK, Lopez-Berestein G, Sood AK (2009) Novel strategies for reversing platinum resistance. Drug Resist Updat 12(6):148–152. https://doi.org/10.1016/j.drup.2009.09.001
Stojanovska V, Sakkal S, Nurgali K (2014) Platinum-based chemotherapy: gastrointestinal immunomodulation and enteric nervous system toxicity. Am J Physiol Gastroint Liver Physiol 308(4):G223–G232. https://doi.org/10.1152/ajpgi.00212.2014
Veronese FM, Pasut G (2005) PEGylation, successful approach to drug delivery. Drug Discov Today 10(21):1451–1458. https://doi.org/10.1016/S1359-6446(05)03575-0
Wernyj RP, Morin PJ (2004) Molecular mechanisms of platinum resistance: still searching for the Achilles’ heel. Drug Resist Updat 7(4):227–232. https://doi.org/10.1016/j.drup.2004.08.002
Acknowledgments
The authors would like to thank Sheikh Bahaei’s research laboratory complex in Science and Research Branch, Islamic Azad University, Tehran, Iran.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that there is no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Hatami, A., Heydarinasab, A., Akbarzadehkhiyavi, A. et al. In vitro co-delivery evaluation of PEGylated nano-liposome loaded by glycyrrhizic acid and cisplatin on cancer cell lines. J Nanopart Res 22, 257 (2020). https://doi.org/10.1007/s11051-020-04982-9
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s11051-020-04982-9