PEGylated Lecithin-Chitosan Nanoparticle-Encapsulated Alphα-Terpineol for In Vitro Anticancer Effects

Overview

Journal AAPS PharmSciTech

Publisher Springer

Specialty Pharmacology

Date 2022 Mar 22

PMID 35314914

Authors

Bahar Zarei

Masoud Homayouni Tabrizi

Amir Rahmati

Affiliations

Soon will be listed here.

Abstract

The aim of this study was to fabrication PEGylated lecithin-chitosan nanoparticles (PLC-NPs) as alphα-Terpineol's (αT-PLC-NPs) delivery system and examine its anti-cancer effects. αT-PLC-NPs were synthesized by self-assembling method; after characterization, entrapment efficiency of α-T was measured by HPLC procedure. MTT test was conducted for cytotoxicity evaluation. Chick chorioallantoic membrane (CAM) and quantitative polymerase chain reaction (qPCR) analysis were used to determine the angiogenesis properties, and qPCR, flow cytometry, and acridine orange and propidium iodide (AO/PI) staining were used to evaluate the pro-apoptotic effects of αT-PLC-NPs. Finally, the anti-inflammatory and antibacterial activity of the αT-PLC-NPs was also evaluated. αT-PLC-NPs with a size of 220.8 nm, polydispersity index (PDI) of 0.3, zeta potential of +29.03 mV, and encapsulation efficiency of 82% showed higher inhibitory effect on MCF7 cells (IC: 750 μg/mL) compared to HFF cells (above 1000 μg/mL). Decreased angiogenesis indices and embryonic growth factors in CAM assay, decreased expression of VEGF and VEGF-R genes, and decreased cell migration showed the inhibitory effect of αT-PLC-NPs on angiogenesis. Increased expression of P53, P21, and caspase9 genes, as well as the results of AO/PI staining along with increasing the number of SubG1 phase cells in flow cytometry, confirmed the pro-apoptotic effects of αT-PLC-NPs. Also, its anti-inflammatory effects were demonstrated by inhibiting the expression of pro-inflammatory cytokines (TNF-α and IL-6). The inhibitory power of αT-PLC-NPs in suppressing gram-positive and negative bacterial strains was demonstrated by disk diffusion (DD), minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) methods. PLC-NPs are a promising carrier for α-T transfer for preclinical studies.

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References

Dai X, Xiang L, Li T, Bai Z . Cancer Hallmarks, Biomarkers and Breast Cancer Molecular Subtypes. J Cancer. 2016; 7(10):1281-94. PMC: 4934037. DOI: 10.7150/jca.13141. View

Fulda S, Debatin K . Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene. 2006; 25(34):4798-811. DOI: 10.1038/sj.onc.1209608. View

Shabestarian H, Homayouni Tabrizi M, Movahedi M, Neamati A, Sharifnia F . Putative mechanism for cancer suppression by PLGA nanoparticles loaded with smoke extract. J Microencapsul. 2021; 38(5):324-337. DOI: 10.1080/02652048.2021.1917715. View

Yan L, Shen J, Wang J, Yang X, Dong S, Lu S . Nanoparticle-Based Drug Delivery System: A Patient-Friendly Chemotherapy for Oncology. Dose Response. 2020; 18(3):1559325820936161. PMC: 7357073. DOI: 10.1177/1559325820936161. View

Moon J, Moxley Jr J, Zhang P, Cui H . Nanoparticle approaches to combating drug resistance. Future Med Chem. 2015; 7(12):1503-10. DOI: 10.4155/fmc.15.82. View

Hassan S, Gali-Muhtasib H, Goransson H, Larsson R . Alpha terpineol: a potential anticancer agent which acts through suppressing NF-kappaB signalling. Anticancer Res. 2010; 30(6):1911-9. View

Held S, Schieberle P, Somoza V . Characterization of alpha-terpineol as an anti-inflammatory component of orange juice by in vitro studies using oral buccal cells. J Agric Food Chem. 2007; 55(20):8040-6. DOI: 10.1021/jf071691m. View

Bicas J, Neri-Numa I, Ruiz A, de Carvalho J, Pastore G . Evaluation of the antioxidant and antiproliferative potential of bioflavors. Food Chem Toxicol. 2011; 49(7):1610-5. DOI: 10.1016/j.fct.2011.04.012. View

Li L, Shi C, Yin Z, Jia R, Peng L, Kang S . Antibacterial activity of α-terpineol may induce morphostructural alterations in Escherichia coli. Braz J Microbiol. 2015; 45(4):1409-13. PMC: 4323317. DOI: 10.1590/s1517-83822014000400035. View

10.

Kong Q, Zhang L, An P, Qi J, Yu X, Lu J . Antifungal mechanisms of α-terpineol and terpene-4-alcohol as the critical components of Melaleuca alternifolia oil in the inhibition of rot disease caused by Aspergillus ochraceus in postharvest grapes. J Appl Microbiol. 2019; 126(4):1161-1174. DOI: 10.1111/jam.14193. View

11.

Dong W, Ye J, Wang W, Yang Y, Wang H, Sun T . Self-Assembled Lecithin/Chitosan Nanoparticles Based on Phospholipid Complex: A Feasible Strategy to Improve Entrapment Efficiency and Transdermal Delivery of Poorly Lipophilic Drug. Int J Nanomedicine. 2020; 15:5629-5643. PMC: 7415465. DOI: 10.2147/IJN.S261162. View

12.

van Hoogevest P . Review - An update on the use of oral phospholipid excipients. Eur J Pharm Sci. 2017; 108:1-12. DOI: 10.1016/j.ejps.2017.07.008. View

13.

Khan M, Madni A, Torchilin V, Filipczak N, Pan J, Tahir N . Lipid-chitosan hybrid nanoparticles for controlled delivery of cisplatin. Drug Deliv. 2019; 26(1):765-772. PMC: 6711028. DOI: 10.1080/10717544.2019.1642420. View

14.

Aibani N, Rai R, Patel P, Cuddihy G, Wasan E . Chitosan Nanoparticles at the Biological Interface: Implications for Drug Delivery. Pharmaceutics. 2021; 13(10). PMC: 8540112. DOI: 10.3390/pharmaceutics13101686. View

15.

Prabaharan M . Chitosan-based nanoparticles for tumor-targeted drug delivery. Int J Biol Macromol. 2014; 72:1313-22. DOI: 10.1016/j.ijbiomac.2014.10.052. View

16.

Ozcan I, Azizoglu E, Senyigit T, Ozyazici M, Ozer O . Enhanced dermal delivery of diflucortolone valerate using lecithin/chitosan nanoparticles: in-vitro and in-vivo evaluations. Int J Nanomedicine. 2013; 8:461-75. PMC: 3564463. DOI: 10.2147/IJN.S40519. View

17.

Ma Q, Gao Y, Sun W, Cao J, Liang Y, Han S . Self-Assembled chitosan/phospholipid nanoparticles: from fundamentals to preparation for advanced drug delivery. Drug Deliv. 2020; 27(1):200-215. PMC: 7034086. DOI: 10.1080/10717544.2020.1716878. View

18.

Ramasamy T, Tran T, Cho H, Kim J, Kim Y, Jeon J . Chitosan-based polyelectrolyte complexes as potential nanoparticulate carriers: physicochemical and biological characterization. Pharm Res. 2013; 31(5):1302-14. DOI: 10.1007/s11095-013-1251-9. View

19.

Veronese F, Pasut G . PEGylation, successful approach to drug delivery. Drug Discov Today. 2005; 10(21):1451-8. DOI: 10.1016/S1359-6446(05)03575-0. View

20.

Kouchakzadeh H, Shojaosadati S, Maghsoudi A, Vasheghani Farahani E . Optimization of PEGylation conditions for BSA nanoparticles using response surface methodology. AAPS PharmSciTech. 2010; 11(3):1206-11. PMC: 2974113. DOI: 10.1208/s12249-010-9487-8. View