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ORIGINAL RESEARCH

Polyvinyl Alcohol (PVA)-Based Nanoniosome for Enhanced in vitro Delivery and Anticancer Activity of Thymol

, , , , , , , , & ORCID Icon show all
Pages 3459-3488 | Received 29 Jan 2023, Accepted 21 Jun 2023, Published online: 27 Jun 2023

References

  • Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–249. doi:10.3322/caac.21660
  • Molani S, Madadi M, Wilkes WJO. A partially observable Markov chain framework to estimate overdiagnosis risk in breast cancer screening: incorporating uncertainty in patients adherence behaviors. Omega. 2019;89:40–53.
  • Jain H, Rajendra A, Sengar M, et al. The current treatment approach to adolescents and young adults with acute lymphoblastic leukemia (AYA-ALL): challenges and considerations. Expert Rev Anticancer Ther. 2022;22(8):845–860. doi:10.1080/14737140.2022.2093718
  • Das CK, Singh SK. Immune Checkpoint Inhibitors in Cancer Therapy: A Ray of Hope, in Biomedical Translational Research. Springer; 2022:393–411.
  • Molani S, Madadi M, Williams DLJM. Investigating the effectiveness of breast cancer supplemental screening considering radiologists’ bias. MedRxiv. 2020;2020:2020.
  • Garmarudi AB. Most common techniques of outlier detection. In: Current Applications of Chemometrics. Nova Science; 2015.
  • Ebrahimi N, Adelian S, Shakerian S, et al. Crosstalk between ferroptosis and the epithelial-mesenchymal transition: implications for inflammation and cancer therapy. Cytokine Growth Factor Rev. 2022;64:33–45. doi:10.1016/j.cytogfr.2022.01.006
  • Namazifard S, Subbarao KJS. Multiple dipole source position and orientation estimation using non-invasive EEG-like signals. Sensors. 2023;23(5):2855. doi:10.3390/s23052855
  • Gezici S, Şekeroğlu N. Current perspectives in the application of medicinal plants against cancer: novel therapeutic agents. Anticancer Agents Med Chem. 2019;19(1):101–111. doi:10.2174/1871520619666181224121004
  • Ahmadi S, Seraj M, Chiani M, et al. In vitro development of controlled-release nanoniosomes for improved delivery and anticancer activity of letrozole for breast cancer treatment. Int J Nanomedicine. 2022;17:6233–6255. doi:10.2147/IJN.S384085
  • Vasan N, Baselga J, Hyman DMJN. A view on drug resistance in cancer. Nature. 2019;575(7782):299–309. doi:10.1038/s41586-019-1730-1
  • Elbe H, Yigitturk G, Cavusoglu T, et al. Apoptotic effects of thymol, a novel monoterpene phenol, on different types of cancer. Bratisl Lek Listy. 2020;121(2):122–128. doi:10.4149/BLL_2020_016
  • Kang S-H, Kim YS, Kim EK, et al. Anticancer effect of thymol on AGS human gastric carcinoma cells. J Microbiol Biotechnol. 2016;26(1):28–37.
  • Haseli S, Pourmadadi M, Samadi A, et al. A novel pH-responsive nanoniosomal emulsion for sustained release of curcumin from a chitosan-based nanocarrier: emphasis on the concurrent improvement of loading, sustained release, and apoptosis induction. Biotechnol Prog. 2022;38(5):e3280. doi:10.1002/btpr.3280
  • Yao Y, Zhou Y, Liu L, et al. Nanoparticle-based drug delivery in cancer therapy and its role in overcoming drug resistance. Front Mol Biosci. 2020;7:193. doi:10.3389/fmolb.2020.00193
  • Chamani E, Ebrahimi R, Khorsandi K, et al. In vitro cytotoxicity of polyphenols from datura innoxia aqueous leaf-extract on human leukemia K562 cells: DNA and nuclear proteins as targets. Drug Chem Toxicol. 2020;43(2):138–148. doi:10.1080/01480545.2019.1629588
  • Bazzazan S, Moeinabadi-Bidgoli K, Lalami ZA, et al. Engineered UIO-66 metal-organic framework for delivery of curcumin against breast cancer cells: an in vitro evaluation. J Drug Deliv Sci Technol. 2023;79:104009.
  • Dastneshan A, Rahiminezhad S, Mezajin MN, et al. Cefazolin encapsulated UiO-66-NH2 nanoparticles enhance the antibacterial activity and biofilm inhibition against drug-resistant S. aureus: in vitro and in vivo studies. Chem Eng J. 2023;455:140544.
  • Kazemi M, Emami J, Hasanzadeh F, et al. In vitro and in vivo evaluation of novel DTX-loaded multifunctional heparin-based polymeric micelles targeting folate receptors and endosomes. Recent Pat Anticancer Drug Discov. 2020;15(4):341–359. doi:10.2174/1574892815666201006124604
  • Rezaei T, Rezaei M, Karimifard S, et al. Folic acid-decorated pH-responsive nanoniosomes with enhanced endocytosis for breast cancer therapy: in vitro studies. Front Pharmacol. 2022;13. doi:10.3389/fphar.2022.851242
  • Akbarzadeh I, Fatemizadeh M, Heidari F, Niri NM. Niosomal formulation for co-administration of hydrophobic anticancer drugs into MCF-7 cancer cells. Arch Adv Biosci. 2020;11(2):1–9.
  • Akbarzadeh I, Saremi Poor A, Yaghmaei S, et al. Niosomal delivery of simvastatin to MDA-MB-231 cancer cells. Drug Dev Ind Pharm. 2020;46(9):1535–1549. doi:10.1080/03639045.2020.1810269
  • Jamshidifar E, Eshrati Yeganeh F, Shayan M, et al. Super magnetic niosomal nanocarrier as a new approach for treatment of breast cancer: a case study on SK-BR-3 and MDA-MB-231 cell lines. Int J Mol Sci. 2021;22(15):7948. doi:10.3390/ijms22157948
  • Amale FR, Ferdowsian S, Hajrasouliha S, et al. Gold nanoparticles loaded into niosomes: a novel approach for enhanced antitumor activity against human ovarian cancer. Adv Powder Technol. 2021;32(12):4711–4722.
  • Kazemi M, Emami J, Hasanzadeh F, et al. Pegylated multifunctional pH-responsive targeted polymeric micelles for ovarian cancer therapy: synthesis, characterization and pharmacokinetic study. Int J Polym Mater Polym Biomater. 2021;70(14):1012–1026.
  • Ge X, Wei M, He S, et al. Advances of non-ionic surfactant vesicles (niosomes) and their application in drug delivery. Pharmaceutics. 2019;11(2):55. doi:10.3390/pharmaceutics11020055
  • Bourbour M, Khayam N, Noorbazargan H, et al. Evaluation of anti-cancer and anti-metastatic effects of folate-PEGylated niosomes for co-delivery of letrozole and ascorbic acid on breast cancer cells. Mol Syst Des Eng. 2022;7(9):1102–1118. doi:10.1016/j.jacbts.2022.05.004
  • Rivera-Hernandez G, Antunes-Ricardo M, Martínez-Morales P, et al. Polyvinyl alcohol based-drug delivery systems for cancer treatment. Int J Pharm. 2021;600:120478. doi:10.1016/j.ijpharm.2021.120478
  • Amiri B, Ahmadvand H, Farhadi A, et al. Delivery of vinblastine-containing niosomes results in potent in vitro/in vivo cytotoxicity on tumor cells. Drug Dev Ind Pharm. 2018;44(8):1371–1376. doi:10.1080/03639045.2018.1451880
  • Baranei M, Taheri RA, Tirgar M, et al. Anticancer effect of green tea extract (GTE)-loaded pH-responsive niosome coated with PEG against different cell lines. Mater Today Commun. 2021;26:101751.
  • Taherkhani A, Fazli H, Taherkhani F. Application of janus magnetic nanoparticle Fe3O4@ SiN functionalized with beta‐cyclodextrin in thymol drug delivery procedure: an in vitro study. Appl Organomet Chem. 2021;35(11):e6399.
  • Karimi E, Abbasi S, Abbasi N, et al. Thymol polymeric nanoparticle synthesis and its effects on the toxicity of high glucose on OEC cells: involvement of growth factors and integrin-linked kinase. Drug Des Devel Ther. 2019;13:2513–2532. doi:10.2147/DDDT.S214454
  • Moghtaderi M, Mirzaie A, Zabet N, et al. Enhanced antibacterial activity of echinacea angustifolia extract against multidrug-resistant Klebsiella pneumoniae through niosome encapsulation. Nanomaterials. 2021;11(6):1573. doi:10.3390/nano11061573
  • Akbarzadeh I, Tavakkoli Yaraki M, Bourbour M, et al. Optimized doxycycline-loaded niosomal formulation for treatment of infection-associated prostate cancer: an in-vitro investigation. J Drug Deliv Sci Technol. 2020;57:101715. doi:10.1016/j.jddst.2020.101715
  • Fahmy UA, Badr-Eldin SM, Ahmed OA, et al. Intranasal niosomal in situ gel as a promising approach for enhancing flibanserin bioavailability and brain delivery: in vitro optimization and ex vivo/in vivo evaluation. Pharmaceutics. 2020;12(6):485.
  • Al-Mahallawi AM, Fares AR, Abd-Elsalam WH. Enhanced permeation of methotrexate via loading into ultra-permeable niosomal vesicles: fabrication, statistical optimization, ex vivo studies, and in vivo skin deposition and tolerability. AAPS PharmSciTech. 2019;20(5):1–10.
  • Zeng W, Li Q, Wan T, et al. Hyaluronic acid-coated niosomes facilitate tacrolimus ocular delivery: mucoadhesion, precorneal retention, aqueous humor pharmacokinetics, and transcorneal permeability. Colloids Surf B Biointerfaces. 2016;141:28–35. doi:10.1016/j.colsurfb.2016.01.014
  • Rochani AK, Balasubramanian S, Ravindran Girija A, et al. Dual mode of cancer cell destruction for pancreatic cancer therapy using Hsp90 inhibitor loaded polymeric nano magnetic formulation. Int J Pharm. 2016;511(1):648–658. doi:10.1016/j.ijpharm.2016.07.048
  • Akbari J, Saeedi M, Enayatifard R, et al. Curcumin niosomes (curcusomes) as an alternative to conventional vehicles: a potential for efficient dermal delivery. J Drug Deliv Sci Technol. 2020;60:102035. doi:10.1016/j.jddst.2020.102035
  • Shaker DS, Shaker MA, Hanafy MS. Cellular uptake, cytotoxicity and in-vivo evaluation of tamoxifen citrate loaded niosomes. Int J Pharm. 2015;493(1–2):285–294. doi:10.1016/j.ijpharm.2015.07.041
  • Noorbazargan H, Mashayekhi A, Khayam N, et al. Anti-cancer, anti-invasiveness & anti-metastasis of green engineered bioorganic-capped silver nanoparticles fabricated from Juniperus chinensis extract and comparison to cisplatin in lung cancer cells (A549): in vitro assessment of cellular and molecular pathways; 2020.
  • Nowroozi F, Almasi A, Javidi J, et al. Effect of surfactant type, cholesterol content and various downsizing methods on the particle size of niosomes. Iran J Pharm Res. 2018;17(Suppl2):1.
  • Yoshioka T, Sternberg B, Florence AT. Preparation and properties of vesicles (niosomes) of sorbitan monoesters (Span 20, 40, 60 and 80) and a sorbitan triester (Span 85). Int J Pharm. 1994;105(1):1–6.
  • García-Manrique P, Machado ND, Fernández MA, et al. Effect of drug molecular weight on niosomes size and encapsulation efficiency. Colloids Surf B Biointerfaces. 2020;186:110711. doi:10.1016/j.colsurfb.2019.110711
  • Kamboj S, Saini V, Bala SJ. Formulation and characterization of drug loaded nonionic surfactant vesicles (niosomes) for oral bioavailability enhancement. Sci World J. 2014;2014:1.
  • Ag Seleci D, Seleci M, Walter JG, Stahl F, Scheper T. Niosomes as nanoparticular drug carriers: fundamentals and recent applications. J Nanomater. 2016;2016:1.
  • Essa EA. Effect of formulation and processing variables on the particle size of sorbitan monopalmitate niosomes. J Nanomater. 2010;4(4):1.
  • Essa EA. Effect of formulation and processing variables on the particle size of sorbitan monopalmitate niosomes. Asian J Pharm. 2014;4(4):1.
  • Moghassemi S, Parnian E, Hakamivala A, et al. Uptake and transport of insulin across intestinal membrane model using trimethyl chitosan coated insulin niosomes. Mater Sci Eng C Mater Biol Appl. 2015;46:333–340. doi:10.1016/j.msec.2014.10.070
  • Waddad AY, Abbad S, Yu F, et al. Formulation, characterization and pharmacokinetics of Morin hydrate niosomes prepared from various non-ionic surfactants. Int J Pharm. 2013;456(2):446–458. doi:10.1016/j.ijpharm.2013.08.040
  • Taymouri S, Varshosaz J. Effect of different types of surfactants on the physical properties and stability of carvedilol nano-niosomes. Adv Biomed Res. 2016;5. doi:10.4103/2277-9175.178781
  • Zaki RM, Ali AA, El Menshawe SF, Bary AA. Formulation and in vitro evaluation of diacerein loaded niosomes. Int J Pharm Pharm Sci. 2014;6(Suppl 2):515–521.
  • Al-Mahallawi AM, Khowessah OM, Shoukri RA. Nano-transfersomal ciprofloxacin loaded vesicles for non-invasive trans-tympanic ototopical delivery: in-vitro optimization, ex-vivo permeation studies, and in-vivo assessment. Int J Pharm. 2014;472(1–2):304–314.
  • Bnyan R, Khan I, Ehtezazi T, et al. Surfactant effects on lipid-based vesicles properties. J Pharm Sci. 2018;107(5):1237–1246. doi:10.1016/j.xphs.2018.01.005
  • Junyaprasert VB, Teeranachaideekul V, Supaperm T. Effect of charged and non-ionic membrane additives on physicochemical properties and stability of niosomes. AAPS pharmscitech. 2008;9:851–859.
  • Manosroi A, Wongtrakul P, Manosroi J, et al. Characterization of vesicles prepared with various non-ionic surfactants mixed with cholesterol. Colloids Surf B Biointerfaces. 2003;30(1–2):129–138.
  • Ruckmani K, Sankar V. Formulation and optimization of zidovudine niosomes. AAPS PharmSciTech. 2010;11(3):1119–1127. doi:10.1208/s12249-010-9480-2
  • Marianecci C, Rinaldi F, Di Marzio L, et al. Ammonium glycyrrhizinate-loaded niosomes as a potential nanotherapeutic system for anti-inflammatory activity in murine models. Int J Nanomedicine. 2014;9:635. doi:10.2147/IJN.S55066
  • Huang Y, Chen J, Chen X, et al. PEGylated synthetic surfactant vesicles (Niosomes): novel carriers for oligonucleotides. J Mater Sci Mater Med. 2008;19(2):607–614. doi:10.1007/s10856-007-3193-4
  • Takeuchi H, Yamamoto H, Toyoda T, et al. Physical stability of size controlled small unilameller liposomes coated with a modified polyvinyl alcohol. Int J Pharm. 1998;164(1–2):103–111.
  • Khalifa A-ZM, Abdul Rasool BK. Optimized mucoadhesive coated niosomes as a sustained oral delivery system of famotidine. AAPS PharmSciTech. 2017;18(8):3064–3075. doi:10.1208/s12249-017-0780-7
  • Cao Y, Liu F, Chen Y, et al. Drug release from core-shell PVA/silk fibroin nanoparticles fabricated by one-step electrospraying. Sci Rep. 2017;7(1):1–9.
  • Kayal S, Ramanujan R, C E. Doxorubicin loaded PVA coated iron oxide nanoparticles for targeted drug delivery. Mater Sci Eng C. 2010;30(3):484–490.
  • Şanlı O, Karaca I, Işıklan N. Preparation, characterization, and salicylic acid release behavior of chitosan/poly (vinyl alcohol) blend microspheres. J Appl Polym Sci. 2009;111(6):2731–2740.
  • Mansoori-Kermani A, Khalighi S, Akbarzadeh I, et al. Engineered hyaluronic acid-decorated niosomal nanoparticles for controlled and targeted delivery of epirubicin to treat breast cancer. Materi Today Bio. 2022;16:100349. doi:10.1016/j.mtbio.2022.100349
  • Karimifard S, Rezaei N, Jamshidifar E, et al. pH-responsive chitosan-adorned niosome nanocarriers for co-delivery of drugs for breast cancer therapy. ACS Appl Nano Mater. 2022;5(7):8811–8825.
  • Mohammadi MR, Malkovskiy AV, Jothimuthu P, et al. PEG/dextran double layer influences Fe ion release and colloidal stability of iron oxide nanoparticles. Sci Rep. 2018;8(1):1–11.
  • Akbarzadeh I, Shayan M, Bourbour M, et al. Preparation, optimization and in-vitro evaluation of curcumin-loaded niosome@calcium alginate nanocarrier as a new approach for breast cancer treatment. Biology. 2021;10(3):173. doi:10.3390/biology10030173
  • Kishore RSK, Pappenberger A, Dauphin IB, et al. Degradation of polysorbates 20 and 80: studies on thermal autoxidation and hydrolysis. J Pharm Sci. 2011;100(2):721–731. doi:10.1002/jps.22290
  • Samadi A, Pourmadadi M, Yazdian F, et al. Ameliorating quercetin constraints in cancer therapy with pH-responsive agarose-polyvinylpyrrolidone -hydroxyapatite nanocomposite encapsulated in double nanoemulsion. Int J Biol Macromol. 2021;182:11–25. doi:10.1016/j.ijbiomac.2021.03.146
  • AbuElfadl A, Boughdady M, Meshali M. New peceol™/span™ 60 niosomes coated with chitosan for candesartan cilexetil: perspective increase in absolute bioavailability in rats. Int J Nanomedicine. 2021;16:5581. doi:10.2147/IJN.S324171
  • Balasubramaniam A, Kumar VA, Pillai KS, et al. Formulation and in vivo evaluation of niosome-encapsulated daunorubicin hydrochloride. Drug Dev Ind Pharm. 2002;28(10):1181–1193. doi:10.1081/ddc-120015351
  • Cosco D, Paolino D, Muzzalupo R, et al. Novel PEG-coated niosomes based on bola-surfactant as drug carriers for 5-fluorouracil. Biomed Microdevices. 2009;11(5):1115–1125. doi:10.1007/s10544-009-9328-2
  • Jamali T, Kavoosi G, Safavi M, Ardestani SK. In-vitro evaluation of apoptotic effect of OEO and thymol in 2D and 3D cell cultures and the study of their interaction mode with DNA. Sci Rep. 2018;8(1):1–19.
  • Blažíčková M, Blaško J, Kubinec R, et al. Newly synthesized thymol derivative and its effect on colorectal cancer cells. Molecules. 2022;27(9):2622. doi:10.3390/molecules27092622
  • Marianecci C, Di Marzio L, Rinaldi F, et al. Niosomes from 80s to present: the state of the art. Adv Colloid Interface Sci. 2014;205:187–206. doi:10.1016/j.cis.2013.11.018
  • Gude RP, Jadhav MG, Rao SGA, et al. Effects of niosomal cisplatin and combination of the same with theophylline and with activated macrophages in murine B16F10 melanoma model. Cancer Biother Radiopharm. 2002;17(2):183–192. doi:10.1089/108497802753773801
  • Uchegbu IF, Double JA, Kelland LR, et al. The activity of doxorubicin niosomes against an ovarian cancer cell line and three in vivo mouse tumour models. J Drug Target. 1996;3(5):399–409. doi:10.3109/10611869608996831
  • Raudszus B, Mulac D, Langer K. A new preparation strategy for surface modified PLA nanoparticles to enhance uptake by endothelial cells. Int J Pharm. 2018;536(1):211–221. doi:10.1016/j.ijpharm.2017.11.047
  • De La Chapa JJ, Singha PK, Lee DR, Gonzales CB. Thymol inhibits oral squamous cell carcinoma growth via mitochondria‐mediated apoptosis. J Oral Pathol Med. 2018;47(7):674–682.
  • Carneiro BA, El-Deiry WS. Targeting apoptosis in cancer therapy. Nat Rev Clin Oncol. 2020;17(7):395–417.
  • Gonzalez-Avila G, Sommer B, Mendoza-Posada DA, et al. Matrix metalloproteinases participation in the metastatic process and their diagnostic and therapeutic applications in cancer. Crit Rev Oncol Hematol. 2019;137:57–83. doi:10.1016/j.critrevonc.2019.02.010
  • Martínez-Alonso D, Malumbres M. Mammalian cell cycle cyclins. In: Seminars in Cell & Developmental Biology. Elsevier; 2020.
  • Haddadian A, Robattorki FF, Dibah H, et al. Niosomes-loaded selenium nanoparticles as a new approach for enhanced antibacterial, anti-biofilm, and anticancer activities. Sci Rep. 2022;12(1):21938. doi:10.1038/s41598-022-26400-x
  • Seresht HR, Albadry BJ, Al-mosawi AK, Gholami O, Cheshomi H. The cytotoxic effects of thymol as the major component of Trachyspermum ammi on breast cancer (MCF-7) cells. Pharm Chem J. 2019;53:101–107.
  • Haghighi A, Shahanipour K, Monajemi R, et al. Evaluation of the cytotoxic effect of thymol loaded chitosan coated Fe3O4 magnetic nanoparticles on MDA-MB-231 cell line and expression of autophagic MAP1LC3A gene. Russ J Bioorg Chem. 2022;2022:1–13.
  • Gali-Muhtasib H, Hmadi R, Kareh M, et al. Cell death mechanisms of plant-derived anticancer drugs: beyond apoptosis. Apoptosis. 2015;20(12):1531–1562. doi:10.1007/s10495-015-1169-2
  • Balan DJ, Das M, Sathya S, et al. Chitosan based encapsulation increased the apoptotic efficacy of thymol on A549 cells and exhibited non toxic response in Swiss albino mice. Int J Biol Macromol. 2022;202:620–631. doi:10.1016/j.ijbiomac.2022.01.093
  • Matthews HK, Bertoli C, de Bruin RA. Cell cycle control in cancer. Nat Rev Mol Cell Biol. 2022;23(1):74–88.
  • Yamada G, Hagiwara Y, Kimura T, et al. Impact of body weight gain on the incidence of nonalcoholic fatty liver disease in nonobese Japanese individuals. Am J Gastroenterol. 2021;116(4):733–748. doi:10.14309/ajg.0000000000001030
  • Islam MT, Khalipha AB, Bagchi R, et al. Anticancer activity of thymol: a literature‐based review and docking study with emphasis on its anticancer mechanisms. IUBMB Life. 2019;71(1):9–19.
  • Avrutsky MI, Troy CM. Caspase-9: a multimodal therapeutic target with diverse cellular expression in human disease. Front Pharmacol. 2021;12:1728.
  • Pourgholi A, Dadashpour M, Mousapour A, et al. Anticancer potential of silibinin loaded polymeric nanoparticles against breast cancer cells: insight into the Apoptotic genes targets. Asian Pac J Cancer Prev. 2021;22(8):2587. doi:10.31557/APJCP.2021.22.8.2587
  • Trachootham D, Alexandre J, Huang P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov. 2009;8(7):579–591. doi:10.1038/nrd2803
  • Perillo B, Di Donato M, Pezone A, et al. ROS in cancer therapy: the bright side of the moon. Exp Mol Med. 2020;52(2):192–203. doi:10.1038/s12276-020-0384-2
  • Infante E, Castagnino A, Ferrari R, et al. LINC complex-Lis1 interplay controls MT1-MMP matrix digest-on-demand response for confined tumor cell migration. Nat Commun. 2018;9(1):1–13.
  • Paudel KR, Wadhwa R, Tew XN, et al. Rutin loaded liquid crystalline nanoparticles inhibit non-small cell lung cancer proliferation and migration in vitro. Life Sci. 2021;276:119436. doi:10.1016/j.lfs.2021.119436
  • Pakizehkar S, Ranji N, Naderi Sohi A, et al. Curcumin loaded PEG400‐OA nanoparticles: a suitable system to increase apoptosis, decrease migration, and deregulate miR‐125b/miR182 in MDA‐MB‐231 human breast cancer cells. Polym Adv Technol. 2020;31(8):1793–1804.
  • Khorani M, Bobe G, Matthews DG, et al. The impact of the hAPP695 SW transgene and associated amyloid-β accumulation on murine hippocampal biochemical pathways. J Alzheimers Dis. 2022;Preprint:1–19.
  • Singhal B, Pandey P, Khan F, Singh SK, Kumar T. In vitro elucidation of antiproliferative and apoptotic effects of thymol against prostate cancer LNCaP cells. 2021.
  • Kumar SR, Thangam R, Vivek R, et al. Synergetic effects of thymoquinone-loaded porous PVPylated Fe3O4 nanostructures for efficient pH-dependent drug release and anticancer potential against triple-negative cancer cells. Nanoscale Adv. 2020;2(8):3209–3221. doi:10.1039/d0na00242a