Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Research Article

Enhancing the Antiproliferative Activity of Perillyl Alcohol against Glioblastoma Cell Lines through Synergistic Formulation with Natural Oils

Author(s): Waleed S. Alharbi*, Abdullah A. Alshehri, Tarek A. Ahmed, Shadab Md., Alshaimaa M. Almehmady, Manal A. Alshabibi, Reem M. Altamimi and Khalid M. El-Say

Volume 30, Issue 14, 2024

Published on: 26 March, 2024

Page: [1075 - 1084] Pages: 10

DOI: 10.2174/0113816128293758240318080527

Price: $65

conference banner
Abstract

Background: Due to its volatility, photostability, and gastrointestinal toxicity, Perillyl Alcohol (POH), a monoterpenoid component of various plant species, is a chemotherapeutic drug with insufficient efficacy. Many naturally occurring bioactive compounds have well-known antiproliferative properties, including sefsol, jojoba, tea tree, and moringa oils.

Objective: This study sought to develop an oil-based Self Nanoemulsifying Drug Delivery System (SNEDDS) using tween 80 as the surfactant and Dimethyl Sulfoxide (DMSO) or Polyethylene Glycol (PEG) 400 as the cosurfactant; the oils were used in a range of 10-20% to boost POH's anticancer efficacy.

Methods: The formulations' size, charge, and impact on the viability of glioma cell lines, ANGM-CSS and A172, were evaluated.

Results: The developed SNEDDS formulations ranged from 3 nm to 362 nm in size, with electronegative surface charges between 5.05 and 17.0 mV and polydispersity indices between 0.3 and 1.0.

Conclusion: The findings indicated that the antiproliferative effect of POH-loaded Nanoemulsion (NE) could be used as a possible anticancer therapy for glioblastoma in vitro, particularly when paired with the tested natural oils. Before asserting that this delivery technique is appropriate for glioblastoma therapy, additional in vitro and in vivo investigations are required.

Keywords: Antiproliferative activity, glioblastoma A172 cells, jojoba oil, moringa oil, perillyl alcohol, self nanoemulsifying drug delivery system.

[1]
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68(6): 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[2]
Ullah A, Aziz T, Ullah N, Nawaz T. Molecular mechanisms of sanguinarine in cancer prevention and treatment. Anticancer Agents Med Chem 2023; 23(7): 765-78.
[http://dx.doi.org/10.2174/1871520622666220831124321] [PMID: 36045531]
[3]
Elimam H, El-Say KM, Cybulsky AV, Khalil H. Regulation of autophagy progress via lysosomal depletion by fluvastatin nanoparticle treatment in breast cancer cells. ACS Omega 2020; 5(25): 15476-86.
[http://dx.doi.org/10.1021/acsomega.0c01618] [PMID: 32637822]
[4]
Fu B, Wang N, Tan HY, Li S, Cheung F, Feng Y. Multi-component herbal products in the prevention and treatment of chemotherapy-associated toxicity and side effects: A review on experimental and clinical evidences. Front Pharmacol 2018; 9: 1394.
[http://dx.doi.org/10.3389/fphar.2018.01394] [PMID: 30555327]
[5]
Ali MA, Mohamed MI, Megahed MA, Abdelghany TM, El-Say KM. Cholesterol-based nanovesicles enhance the in vitro cytotoxicity, ex vivo intestinal absorption, and in vivo bioavailability of flutamide. Pharmaceutics 2021; 13(11): 1741.
[http://dx.doi.org/10.3390/pharmaceutics13111741] [PMID: 34834155]
[6]
Ahmed T, Ali E, Omar A, Almehmady A, El-Say K. Enhancing ezetimibe anticancer activity through development of drug nano-micelles formulations: A promising strategy supported by molecular docking. Int J Nanomed 2023; 18(November): 6689-703.
[http://dx.doi.org/10.2147/IJN.S438704] [PMID: 38026536]
[7]
Kassem MA, El-Sawy HS, Abd-Allah FI, Abdelghany TM, El-Say KM. Maximizing the therapeutic efficacy of imatinib mesylate–loaded niosomes on human colon adenocarcinoma using box-behnken design. J Pharm Sci 2017; 106(1): 111-22.
[http://dx.doi.org/10.1016/j.xphs.2016.07.007] [PMID: 27544432]
[8]
Cragg GM, Pezzuto JM. Natural products as a vital source for the discovery of cancer chemotherapeutic and chemopreventive agents. Med Princ Pract 2016; 25(Suppl 2) (Suppl. 2): 41-59.
[http://dx.doi.org/10.1159/000443404] [PMID: 26679767]
[9]
El-Sawy HS, Al-Abd AM, Ahmed TA, El-Say KM, Torchilin VP. Stimuli-responsive nano-architecture drug-delivery systems to solid tumor micromilieu: Past, present, and future perspectives. ACS Nano 2018; 12(11): 10636-64.
[http://dx.doi.org/10.1021/acsnano.8b06104] [PMID: 30335963]
[10]
Nwodo JN, Ibezim A, Simoben CV, Ntie-Kang F. Exploring cancer therapeutics with natural products from african medicinal plants, part II: Alkaloids, terpenoids and flavonoids. Anticancer Agents Med Chem 2016; 16(1): 108-27.
[http://dx.doi.org/10.2174/1871520615666150520143827] [PMID: 25991425]
[11]
Khan NU, Razzaq A, Rui Z, et al. Bio-evaluations of sericin coated hesperidin nanoparticles for gastric ulcer management. Colloids Surf B Biointerfaces 2024; 234: 113762.
[http://dx.doi.org/10.1016/j.colsurfb.2024.113762] [PMID: 38244483]
[12]
Sak K. Cytotoxicity of dietary flavonoids on different human cancer types. Pharmacogn Rev 2014; 8(16): 122-46.
[http://dx.doi.org/10.4103/0973-7847.134247] [PMID: 25125885]
[13]
Dehelean CA, Marcovici I, Soica C, et al. Plant-derived anticancer compounds as new perspectives in drug discovery and alternative therapy. Molecules 2021; 26(4): 1109.
[http://dx.doi.org/10.3390/molecules26041109] [PMID: 33669817]
[14]
Øverby A, Zhao CM, Chen D. Plant phytochemicals: Potential anticancer agents against gastric cancer. Curr Opin Pharmacol 2014; 19: 6-10.
[http://dx.doi.org/10.1016/j.coph.2014.05.010] [PMID: 24929966]
[15]
Iqbal J, Abbasi BA, Mahmood T, et al. Plant-derived anticancer agents: A green anticancer approach. Asian Pac J Trop Biomed 2017; 7(12): 1129-50.
[http://dx.doi.org/10.1016/j.apjtb.2017.10.016]
[16]
Huang M, Lu JJ, Huang MQ, Bao JL, Chen XP, Wang YT. Terpenoids: Natural products for cancer therapy. Expert Opin Investig Drugs 2012; 21(12): 1801-18.
[http://dx.doi.org/10.1517/13543784.2012.727395] [PMID: 23092199]
[17]
Amawi H, Ashby CR Jr, Tiwari AK. Cancer chemoprevention through dietary flavonoids: What’s limiting? Chin J Cancer 2017; 36(1): 50.
[http://dx.doi.org/10.1186/s40880-017-0217-4] [PMID: 28629389]
[18]
Kumar V, Bhatt P, Rahman M, et al. Fabrication, optimization, and characterization of umbelliferone β-D-galactopyranoside-loaded PLGA nanoparticles in treatment of hepatocellular carcinoma: in vitro and in vivo studies. Int J Nanomed 2017; 12: 6747-58.
[http://dx.doi.org/10.2147/IJN.S136629] [PMID: 28932118]
[19]
El-Say KM, El-Sawy HS. Polymeric nanoparticles: Promising platform for drug delivery. Int J Pharm 2017; 528(1-2): 675-91.
[http://dx.doi.org/10.1016/j.ijpharm.2017.06.052] [PMID: 28629982]
[20]
Chen TC, da Fonseca CO, Levin D, Schönthal AH. The monoterpenoid perillyl alcohol: Anticancer agent and medium to overcome biological barriers. Pharmaceutics 2021; 13(12): 2167.
[http://dx.doi.org/10.3390/pharmaceutics13122167] [PMID: 34959448]
[21]
Dionísio AP, Molina G, de Carvalho DS, Dos Santos R, Bicas JL, Pastore GM. Natural flavourings from biotechnology for foods and beverages. Natural food additives, ingredients and flavourings. Elsevier 2012; pp. 231-59.
[http://dx.doi.org/10.1533/9780857095725.1.231]
[22]
Ahmed TA, Almehmady AM, Alharbi WS, et al. Incorporation of perillyl alcohol into lipid-based nanocarriers enhances the antiproliferative activity in malignant glioma cells. Biomedicines 2023; 11(10): 2771.
[http://dx.doi.org/10.3390/biomedicines11102771] [PMID: 37893144]
[23]
Yuri T, Danbara N, Tsujita-Kyutoku M, et al. Perillyl alcohol inhibits human breast cancer cell growth in vitro and in vivo. Breast Cancer Res Treat 2004; 84(3): 251-60.
[http://dx.doi.org/10.1023/B:BREA.0000019966.97011.4d] [PMID: 15026623]
[24]
Sundin T, Peffley DM, Gauthier D, Hentosh P. The isoprenoid perillyl alcohol inhibits telomerase activity in prostate cancer cells. Biochimie 2012; 94(12): 2639-48.
[http://dx.doi.org/10.1016/j.biochi.2012.07.028] [PMID: 22902867]
[25]
Crowell PL, Lin S, Vedejs E, Gould MN. Identification of metabolites of the antitumor agentd-limonene capable of inhibiting protein isoprenylation and cell growth. Cancer Chemother Pharmacol 1992; 31(3): 205-12.
[http://dx.doi.org/10.1007/BF00685549] [PMID: 1464157]
[26]
Crowell PL, Chang RR, Ren ZB, Elson CE, Gould MN. Selective inhibition of isoprenylation of 21-26-kDa proteins by the anticarcinogen d-limonene and its metabolites. J Biol Chem 1991; 266(26): 17679-85.
[http://dx.doi.org/10.1016/S0021-9258(19)47425-5] [PMID: 1894647]
[27]
Wiseman DA, Werner SR, Crowell PL. Cell cycle arrest by the isoprenoids perillyl alcohol, geraniol, and farnesol is mediated by p21(Cip1) and p27(Kip1) in human pancreatic adenocarcinoma cells. J Pharmacol Exp Ther 2007; 320(3): 1163-70.
[http://dx.doi.org/10.1124/jpet.106.111666] [PMID: 17138864]
[28]
Koyama M, Sowa Y, Hitomi T, et al. Perillyl alcohol causes G1 arrest through p15INK4b and p21WAF1/Cip1 induction. Oncol Rep 2013; 29(2): 779-84.
[http://dx.doi.org/10.3892/or.2012.2167] [PMID: 23233050]
[29]
Ripple GH, Gould MN, Arzoomanian RZ, et al. Phase I clinical and pharmacokinetic study of perillyl alcohol administered four times a day. Clin Cancer Res 2000; 6(2): 390-6.
[PMID: 10690515]
[30]
Kennedy D, Okello E, Chazot P, et al. Volatile terpenes and brain function: Investigation of the cognitive and mood effects of Mentha× Piperita L. essential oil with in vitro properties relevant to central nervous system function. Nutrients 2018; 10(8): 1029.
[http://dx.doi.org/10.3390/nu10081029] [PMID: 30087294]
[31]
Seca A, Pinto D. Plant secondary metabolites as anticancer agents: Successes in clinical trials and therapeutic application. Int J Mol Sci 2018; 19(1): 263.
[http://dx.doi.org/10.3390/ijms19010263] [PMID: 29337925]
[32]
Rahman M, Ahmad MZ, Kazmi I, et al. Advancement in multifunctional nanoparticles for the effective treatment of cancer. Expert Opin Drug Deliv 2012; 9(4): 367-81.
[http://dx.doi.org/10.1517/17425247.2012.668522] [PMID: 22400808]
[33]
Rahman M, Zaki Ahmad M, Kazmi I, et al. Emergence of nanomedicine as cancer targeted magic bullets: Recent development and need to address the toxicity apprehension. Curr Drug Discov Technol 2012; 9(4): 319-29.
[http://dx.doi.org/10.2174/157016312803305898] [PMID: 22725687]
[34]
Tan AC, Ashley DM, López GY, Malinzak M, Friedman HS, Khasraw M. Management of glioblastoma: State of the art and future directions. CA Cancer J Clin 2020; 70(4): 299-312.
[http://dx.doi.org/10.3322/caac.21613] [PMID: 32478924]
[35]
Ohgaki H, Kleihues P. The definition of primary and secondary glioblastoma. Clin Cancer Res 2013; 19(4): 764-72.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-3002] [PMID: 23209033]
[36]
Johnson DR, Fogh SE, Giannini C, Kaufmann TJ, Raghunathan A, Theodosopoulos PV. Case-based review: Newly diagnosed glioblastoma. Neuro-Oncology Pract 2015; 2(3): 106-21.
[http://dx.doi.org/10.1093/nop/npv020]
[37]
Ellor SV, Pagano-Young TA, Avgeropoulos NG. Glioblastoma: Background, standard treatment paradigms, and supportive care considerations. J Law Med Ethics 2014; 42(2): 171-82.
[PMID: 25040381]
[38]
Moliterno Günel J, Piepmeier JM, Baehring JM. Malignant Brain Tumors. Malignant Brain Tumors: State-of-the-Art Treatment. Cham: Springer International Publishing 2017; pp. 1-97.
[http://dx.doi.org/10.1007/978-3-319-49864-5]
[39]
Date AA, Desai N, Dixit R, Nagarsenker M. Self-nanoemulsifying drug delivery systems: Formulation insights, applications and advances. Nanomedicine 2010; 5(10): 1595-616.
[http://dx.doi.org/10.2217/nnm.10.126] [PMID: 21143036]
[40]
Aldawsari HM, Elfaky MA, Fahmy UA, Aljaeid BM, Alshareef OA, El-Say KM. Development of a fluvastatin-loaded self-nanoemulsifying system to maximize therapeutic efficacy in human colorectal carcinoma cells. J Drug Deliv Sci Technol 2018; 46(April): 7-13.
[http://dx.doi.org/10.1016/j.jddst.2018.04.015]
[41]
El-Say KM, Ahmed TA, Ahmed OAA, Hosny KM, Abd-Allah FI. Self-nanoemulsifying lyophilized tablets for flash oral transmucosal delivery of vitamin K: Development and clinical evaluation. J Pharm Sci 2017; 106(9): 2447-56.
[http://dx.doi.org/10.1016/j.xphs.2017.01.001] [PMID: 28087316]
[42]
Bhagwat DA, Swami PA, Nadaf SJ, et al. Capsaicin loaded solid SNEDDS for enhanced bioavailability and anticancer activity: In- vitro, in-silico, and in-vivo characterization. J Pharm Sci 2021; 110(1): 280-91.
[http://dx.doi.org/10.1016/j.xphs.2020.10.020] [PMID: 33069713]
[43]
Ahmed T, Ali E, Kalantan A, Almehmady A, El-Say K. Exploring the enhanced antiproliferative activity of turmeric oil and 6-mercaptopurine in a combined nano-particulate system formulation. Pharmaceutics 2023; 15(7): 1901.
[http://dx.doi.org/10.3390/pharmaceutics15071901] [PMID: 37514087]
[44]
Elimam H, Hussein J, Abdel-Latif Y, Abdel-Aziz AK, El-Say KM. Preclinical activity of fluvastatin-loaded self-nanoemulsifying delivery system against breast cancer models: Emphasis on apoptosis. J Cell Biochem 2022; 123(5): 947-63.
[http://dx.doi.org/10.1002/jcb.30238] [PMID: 35342983]
[45]
Larsen A, Ogbonna A, Abu-Rmaileh R, Abrahamsson B, Østergaard J, Müllertz A. SNEDDS containing poorly water soluble cinnarizine; Development and in vitro characterization of dispersion, digestion and solubilization. Pharmaceutics 2012; 4(4): 641-65.
[http://dx.doi.org/10.3390/pharmaceutics4040641] [PMID: 24300374]
[46]
Karavasili C, Andreadis II, Tsantarliotou MP, et al. Self-nanoemulsifying drug delivery systems (SNEDDS) containing rice bran oil for enhanced fenofibrate oral delivery: In vitro digestion, ex vivo permeability, and in vivo bioavailability studies. AAPS PharmSciTech 2020; 21(6): 208.
[http://dx.doi.org/10.1208/s12249-020-01765-2] [PMID: 32725343]
[47]
Qu Y, Li A, Ma L, et al. Nose-to-brain delivery of disulfiram nanoemulsion in situ gel formulation for glioblastoma targeting therapy. Int J Pharm 2021; 597: 120250.
[http://dx.doi.org/10.1016/j.ijpharm.2021.120250] [PMID: 33486040]
[48]
Al-Subaie MM, Hosny KM, El-Say KM, Ahmed TA, Aljaeid BM. Utilization of nanotechnology to enhance percutaneous absorption of acyclovir in the treatment of herpes simplex viral infections. Int J Nanomed 2015; 10: 3973-85.
[PMID: 26109856]
[49]
Bandyopadhyay S, Katare OP, Singh B. Optimized self nano-emulsifying systems of ezetimibe with enhanced bioavailability potential using long chain and medium chain triglycerides. Colloids Surf B Biointerfaces 2012; 100: 50-61.
[http://dx.doi.org/10.1016/j.colsurfb.2012.05.019] [PMID: 22766282]
[50]
Parmar N, Singla N, Amin S, Kohli K. Study of cosurfactant effect on nanoemulsifying area and development of lercanidipine loaded (SNEDDS) self nanoemulsifying drug delivery system. Colloids Surf B Biointerfaces 2011; 86(2): 327-38.
[http://dx.doi.org/10.1016/j.colsurfb.2011.04.016] [PMID: 21550214]
[51]
Alshaya HA, Alfahad AJ, Alsulaihem FM, et al. Fast-dissolving nifedipine and atorvastatin calcium electrospun nanofibers as a potential buccal delivery system. Pharmaceutics 2022; 14(2): 358.
[http://dx.doi.org/10.3390/pharmaceutics14020358] [PMID: 35214093]
[52]
Alzahrani NM, Booq RY, Aldossary AM, et al. Liposome-encapsulated tobramycin and IDR-1018 peptide mediated biofilm disruption and enhanced antimicrobial activity against Pseudomonas aeruginosa. Pharmaceutics 2022; 14(5): 960.
[http://dx.doi.org/10.3390/pharmaceutics14050960] [PMID: 35631547]
[53]
Ahmed OAA, Badr-Eldin SM, Tawfik MK, Ahmed TA, El-Say KM, Badr JM. Design and optimization of self-nanoemulsifying delivery system to enhance quercetin hepatoprotective activity in paracetamol-induced hepatotoxicity. J Pharm Sci 2014; 103(2): 602-12.
[http://dx.doi.org/10.1002/jps.23834] [PMID: 24395640]
[54]
Williams AC, Barry BW. Penetration enhancers. Adv Drug Deliv Rev 2004; 56(5): 603-18.
[http://dx.doi.org/10.1016/j.addr.2003.10.025] [PMID: 15019749]
[55]
Azeem A, Rizwan M, Ahmad FJ, et al. Nanoemulsion components screening and selection: A technical note. AAPS PharmSciTech 2009; 10(1): 69-76.
[http://dx.doi.org/10.1208/s12249-008-9178-x] [PMID: 19148761]
[56]
Yadav SK, Mishra S, Mishra B. Eudragit-based nanosuspension of poorly water-soluble drug: Formulation and in vitro-in vivo evaluation. AAPS PharmSciTech 2012; 13(4): 1031-44.
[http://dx.doi.org/10.1208/s12249-012-9833-0] [PMID: 22893314]
[57]
Balakumar K, Raghavan CV, selvan NT, prasad RH, Abdu S. Self nanoemulsifying drug delivery system (SNEDDS) of Rosuvastatin calcium: Design, formulation, bioavailability and pharmacokinetic evaluation. Colloids Surf B Biointerfaces 2013; 112: 337-43.
[http://dx.doi.org/10.1016/j.colsurfb.2013.08.025] [PMID: 24012665]
[58]
Parker DJ, Chong ST, Hasell T. Sustainable inverse-vulcanised sulfur polymers. RSC Advances 2018; 8(49): 27892-9.
[http://dx.doi.org/10.1039/C8RA04446E] [PMID: 35542731]
[59]
Alamer AA, Alsaleh NB, Aodah AH, et al. Development of imeglimin electrospun nanofibers as a potential buccal antidiabetic therapeutic approach. Pharmaceutics 2023; 15(4): 1208.
[http://dx.doi.org/10.3390/pharmaceutics15041208] [PMID: 37111693]
[60]
Andrade S, Ramalho MJ, Pereira MC, Loureiro JA. Resveratrol brain delivery for neurological disorders prevention and treatment. Front Pharmacol 2018; 9(NOV): 1261.
[http://dx.doi.org/10.3389/fphar.2018.01261] [PMID: 30524273]
[61]
Gad HA, Roberts A, Hamzi SH, et al. Jojoba oil: An updated comprehensive review on chemistry, pharmaceutical uses, and toxicity. Polymers 2021; 13(11): 1711. https://www.mdpi.com/2073-4360/13/11/1711
[http://dx.doi.org/10.3390/polym13111711] [PMID: 34073772]
[62]
Abou-Zeid SM, Tahoun EA, AbuBakr HO. Ameliorative effects of jojoba oil on fipronil-induced hepatorenal- and neuro-toxicity: The antioxidant status and apoptotic markers expression in rats. Environ Sci Pollut Res Int 2021; 28(20): 25959-71.
[http://dx.doi.org/10.1007/s11356-020-12083-2] [PMID: 33481197]
[63]
Masyita A, Mustika Sari R, Dwi Astuti A, Yasir B, Rahma Rumata N, Emran T. Terpenes and terpenoids as main bioactive compounds of essential oils, their roles in human health and potential application as natural food preservatives. Food Chem X 2022; 13: 100217.
[64]
Antonietta A, Maria AO, Sabrina S, et al. Tea tree oil a new natural adjuvant for inhibiting glioblastoma growth. J Pharmacogn Phytother 2019; 11(3): 61-73.
[http://dx.doi.org/10.5897/JPP2019.0549]
[65]
Assmann CE, Cadoná FC, Bonadiman BSR, Dornelles EB, Trevisan G, Cruz IBM. Tea tree oil presents in vitro antitumor activity on breast cancer cells without cytotoxic effects on fibroblasts and on peripheral blood mononuclear cells. Biomed Pharmacother 2018; 103: 1253-61.
[http://dx.doi.org/10.1016/j.biopha.2018.04.096] [PMID: 29864906]
[66]
Singh J, Gautam DNS, Sourav S, Sharma R. Role of Moringa oleifera Lam. in cancer: Phytochemistry and pharmacological insights. Food Front 2023; 4(1): 164-206.
[http://dx.doi.org/10.1002/fft2.181]

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