ADVANCING CURCUMIN APPLICATIONS IN HEPATOCELLULAR CARCINOMA: INSIGHTS INTO PHARMACOKINETICS, PHARMACODYNAMICS AND NANODELIVERY SYSTEMS
DOI:
https://doi.org/10.22159/ijap.2025v17i4.53730Keywords:
Hepatocellular carcinoma, Curcumin, Pharmacokinetics, Pharmacodynamics, Cancer, TumorAbstract
This review explores therapeutic potential of curcumin (CU) in Hepato Cellular Carcinoma (HCC), with a focus on its molecular mechanisms of action and the strategies developed to overcome its clinical limitations.
CU exerts anti-cancer effects by modulating critical signaling pathways, including Wingless Integration site1/β-Catenin) Wnt/β-catenin, Phosphatidyl Inositol 3-Kinase, and Protein Kinase B (PI3K/Akt), Mitogen-Activated Protein Kinase (MAPK) and Nuclear Factor Kappa B (NF-κB), thereby inhibiting the progression of HCC. It induces Growth 1/Synthesis (G1/S) phase cell cycle arrest, triggers apoptosis via the mitochondrial pathway and activates tumor suppressor genes such as tumor Protein p53 (p53). Additionally, it demonstrates anti-angiogenic activity through downregulation of Vascular Endothelial Growth Factor (VEGF) and exhibits antioxidant properties by neutralizing Reactive Oxygen Species (ROS) and enhancing the activity of antioxidant enzymes like Super Oxide Dismutase (SOD). However, despite these promising pharmacological actions, CU’s poor systemic bioavailability remains a significant barrier to its clinical application. Nanoparticle-based delivery systems have emerged as a promising solution to improve its stability and absorption.
This review offers an updated perspective by integrating CU’s anti-tumor mechanisms with recent advancements in nanotechnology-based delivery approaches for HCC. Unlike earlier studies, it emphasizes the role of novel nanocarriers-such as Liposomes (LP), Solid Lipid Nanoparticles (SLNs), Nanostructured Lipid Carriers (NLCs) and Resealed Erythrocytes (RE)-in enhancing CU’s bioavailability and tumor-targeting capabilities. These advanced delivery systems improve cellular uptake, extend circulation time and enhance therapeutic efficacy by addressing the pharmacokinetic limitations of CU. The review provides a comprehensive foundation for the translation of nanotechnology-enabled CU therapies into clinical applications for HCC.
CU represents a versatile therapeutic candidate for HCC, modulating tumor development and progression through multiple molecular pathways. Enhancing its bioavailability via advanced nanocarrier systems is essential to fully realize its clinical potential and therapeutic effectiveness.
References
Coffman D Annibale K, Xie C, Hrones DM, Ghabra S, Greten TF, Monge C. The current landscape of therapies for hepatocellular carcinoma. Carcinogenesis. 2023;44(7):537-48. doi: 10.1093/carcin/bgad052, PMID 37428789.
Chivate A, Pratibha S, Salve, Rajendra C, Doijad, Avinash M, Mane, Niranjan D, Chivate. Effect of capecitabine resealed erythrocytes on mnu induced hepatocarcinogenesis in swiss albino mice. PCI-Approved-IJPSN. 2022;15(1):5813-21. doi: 10.37285/ijpsn.2022.15.1.9.
Raza A, Sood GK. Hepatocellular carcinoma review: current treatment and evidence-based medicine. World J Gastroenterol. 2014;20(15):4115-27. doi: 10.3748/wjg.v20.i15.4115, PMID 24764650.
Lee MJ. A review of liver fibrosis and cirrhosis regression. J Pathol Transl Med. 2023;57(4):189-95. doi: 10.4132/jptm.2023.05.24.
Desai A, Sandhu S, Lai JP, Sandhu DS. Hepatocellular carcinoma in non-cirrhotic liver: a comprehensive review. World J Hepatol. 2019;11(1):1-18. doi: 10.4254/wjh.v11.i1.1, PMID 30705715.
Ramakrishna G, Rastogi A, Trehanpati N, Sen B, Khosla R, Sarin SK. From cirrhosis to hepatocellular carcinoma: new molecular insights on inflammation and cellular senescence. Liver Cancer. 2013;2(3-4):367-83. doi: 10.1159/000343852, PMID 24400224.
Stroffolini T, Stroffolini G. A historical overview on the role of hepatitis B and C viruses as aetiological factors for hepatocellular carcinoma. Cancers. 2023;15(8):2388. doi: 10.3390/cancers15082388, PMID 37190317.
Chivate AN, Salve PS, Doijad RC, Mane AM, Chivate ND. Acute toxicity study of intravenously administered capecitabine resealed erythrocytes in mice. Res J Pharm Technol. 2022;15(12):5473-7. doi: 10.52711/0974-360X.2022.00923.
Steffi PF, MS. Curcumin a potent anticarcinogenic polyphenol a review. Asian J Pharm Clin Res. 2014;7(7):1-8.
Asish A, Rajan S, Jose SP, SS, MR, SS. Extracellular modulatory and anti-inflammatory effects of a combination of curcumin piperine and virgin coconut oil in animal model. Asian J Pharm Clin Res. 2024;17(2):73-9. doi: 10.22159/ajpcr.2024v17i12.52641.
Kaur J, Bawa P, Rajesh SY, Sharma P, Ghai D, Jyoti J. Formulation of curcumin nanosuspension using box-behnken design and study of impact of drying techniques on its powder characteristics. Asian J Pharm Clin Res. 2017;10(16):43-51. doi: 10.22159/ajpcr.2017.v10s4.21335.
Sia D, Villanueva A, Friedman SL, Llovet JM. Liver cancer cell of origin molecular class and effects on patient prognosis. Gastroenterology. 2017;152(4):745-61. doi: 10.1053/j.gastro.2016.11.048, PMID 28043904.
Pikarsky E. Neighbourhood deaths cause a switch in cancer subtype. Nature. 2018;562(7725):45-6. doi: 10.1038/d41586-018-06217-3, PMID 30275548.
Schulze K, Imbeaud S, Letouze E, Alexandrov LB, Calderaro J, Rebouissou S. Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets. Nat Genet. 2015;47(5):505-11. doi: 10.1038/ng.3252, PMID 25822088.
Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021;7(1):6. doi: 10.1038/s41572-020-00240-3, PMID 33479224.
Hyman DM, Taylor BS, Baselga J. Implementing genome driven oncology. Cell. 2017;168(4):584-99. doi: 10.1016/j.cell.2016.12.015, PMID 28187282.
Bhutadiya VL, Mistry KN. A review on bioactive phytochemicals and its mechanism on cancer treatment and prevention by targeting multiple cellular signaling pathways. Int J Pharm Pharm Sci. 2021;13(12):15-9. doi: 10.22159/ijpps.2021v13i12.42798.
European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of hepatocellular carcinoma. J Hepatol. 2018;69(1):182-236. doi: 10.1016/j.jhep.2018.03.019, PMID 29628281.
Paterlini Brechot P, Saigo K, Murakami Y, Chami M, Gozuacik D, Mugnier C. Hepatitis B virus related insertional mutagenesis occurs frequently in human liver cancers and recurrently targets human telomerase gene. Oncogene. 2003;22(25):3911-6. doi: 10.1038/sj.onc.1206492, PMID 12813464.
Nault JC, Datta S, Imbeaud S, Franconi A, Mallet M, Couchy G. Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas. Nat Genet. 2015;47(10):1187-93. doi: 10.1038/ng.3389, PMID 26301494.
Bayard Q, Meunier L, Peneau C, Renault V, Shinde J, Nault JC. Cyclin A2/E1 activation defines a hepatocellular carcinoma subclass with a rearrangement signature of replication stress. Nat Commun. 2018;9(1):5235. doi: 10.1038/s41467-018-07552-9, PMID 30531861.
Alexandrov LB, Nik Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV. Signatures of mutational processes in human cancer. Nature. 2013;500(7463):415-21. doi: 10.1038/nature12477, PMID 23945592.
Zucman Rossi J, Villanueva A, Nault JC, Llovet JM. Genetic landscape and biomarkers of hepatocellular carcinoma. Gastroenterology. 2015;149(5):1226-39.e4. doi: 10.1053/j.gastro.2015.05.061, PMID 26099527.
Cancer Genome Atlas Research Network. Electronic address: wheeler@bcm.edu, cancer genome atlas research network. comprehensive and integrative genomic characterization of hepatocellular carcinoma. Cell. 2017;169(7):1327-41.e23. doi: 10.1016/j.cell.2017.05.046, PMID 28622513.
Lachenmayer A, Alsinet C, Savic R, Cabellos L, Toffanin S, Hoshida Y. Wnt-pathway activation in two molecular classes of hepatocellular carcinoma and experimental modulation by sorafenib. Clin Cancer Res. 2012;18(18):4997-5007. doi: 10.1158/1078-0432.CCR-11-2322, PMID 22811581.
Bruno TC. New predictors for immunotherapy responses sharpen our view of the tumour microenvironment. Nature. 2020;577(7791):474-6. doi: 10.1038/d41586-019-03943-0, PMID 31965091.
Ruiz DE Galarreta M, Bresnahan E, Molina Sanchez P, Lindblad KE, Maier B, Sia D. β-catenin activation promotes immune escape and resistance to anti-PD-1 therapy in hepatocellular carcinoma. Cancer Discov. 2019;9(8):1124-41. doi: 10.1158/2159-8290.CD-19-0074, PMID 31186238.
Sia D, Jiao Y, Martinez Quetglas I, Kuchuk O, Villacorta Martin C, Castro DE Moura M. Identification of an immune-specific class of hepatocellular carcinoma based on molecular features. Gastroenterology. 2017;153(3):812-26. doi: 10.1053/j.gastro.2017.06.007, PMID 28624577.
Anstee QM, Reeves HL, Kotsiliti E, Govaere O, Heikenwalder M. From NASH to HCC: current concepts and future challenges. Nat Rev Gastroenterol Hepatol. 2019;16(7):411-28. doi: 10.1038/s41575-019-0145-7, PMID 31028350.
Gomes AL, Teijeiro A, Buren S, Tummala KS, Yilmaz M, Waisman A. Metabolic inflammation-associated IL-17A causes non-alcoholic steatohepatitis and hepatocellular carcinoma. Cancer Cell. 2016;30(1):161-75. doi: 10.1016/j.ccell.2016.05.020, PMID 27411590.
Tsuchida T, Friedman SL. Mechanisms of hepatic stellate cell activation. Nat Rev Gastroenterol Hepatol. 2017 Jul;14(7):397-411. doi: 10.1038/nrgastro.2017.38, PMID 28487545.
Moeini A, Torrecilla S, Tovar V, Montironi C, Andreu Oller C, Peix J. An immune gene expression signature associated with development of human hepatocellular carcinoma identifies mice that respond to chemopreventive agents. Gastroenterology. 2019 Nov;157(5):1383-97.e11. doi: 10.1053/j.gastro.2019.07.028, PMID 31344396.
Hoshida Y, Villanueva A, Sangiovanni A, Sole M, Hur C, Andersson KL. Prognostic gene expression signature for patients with hepatitis C-related early-stage cirrhosis. Gastroenterology. 2013 May;144(5):1024-30. doi: 10.1053/j.gastro.2013.01.021, PMID 23333348.
Pietta PG. Flavonoids as antioxidants. J Nat Prod. 2000 Jul;63(7):1035-42. doi: 10.1021/np9904509, PMID 10924197.
Kawai M, Hirano T, Higa S, Arimitsu J, Maruta M, Kuwahara Y. Flavonoids and related compounds as anti-allergic substances. Allergol Int. 2007 Jan;56(2):113-23. doi: 10.2332/allergolint.R-06-135, PMID 17384531.
Serafini M, Peluso I, Raguzzini A. Flavonoids as anti-inflammatory agents. Proc Nutr Soc. 2010 Aug;69(3):273-8. doi: 10.1017/S002966511000162X, PMID 20569521.
Panche AN, Diwan AD, Chandra SR. Flavonoids: an overview. J Nutr Sci. 2016 Dec 29;5:e47. doi: 10.1017/jns.2016.41, PMID 28620474.
Chahar MK, Sharma N, Dobhal MP, Joshi YC. Flavonoids: a versatile source of anticancer drugs. Pharmacogn Rev. 2011;5(9):1-12. doi: 10.4103/0973-7847.79093, PMID 22096313.
Sak K. Cytotoxicity of dietary flavonoids on different human cancer types. Pharmacogn Rev. 2014;8(16):122-46. doi: 10.4103/0973-7847.134247, PMID 25125885.
Ren W, Qiao Z, Wang H, Zhu L, Zhang L. Flavonoids: promising anticancer agents. Med Res Rev. 2003;23(4):519-34. doi: 10.1002/med.10033, PMID 12710022.
MA T, Fan A, LV C, Cao J, Ren K. Screening flavonoids and their synthetic analogs to target liver cancer stem-like cells. Int J Clin Exp Med. 2018;11(10):10614-22.
Fuloria S, Mehta J, Chandel A, Sekar M, Rani NN, Begum MY. A comprehensive review on the therapeutic potential of Curcuma longa Linn. in relation to its major active constituent curcumin. Front Pharmacol. 2022 Mar 25;13:820806. doi: 10.3389/fphar.2022.820806, PMID 35401176.
Lestari ML, Indrayanto G. Curcumin. Profiles Drug Subst Excip Relat Methodol. 2014;39:113-204. doi: 10.1016/B978-0-12-800173-8.00003-9, PMID 24794906.
Proenca Assuncao JC, Constantino E, Farias DE França AP, Nogueira FA, Consonni SR, Chaud MV. Mutagenicity of silver nanoparticles synthesized with curcumin (Cur-AgNPs). J Saudi Chem Soc. 2021 Sep;25(9):101321. doi: 10.1016/j.jscs.2021.101321.
Hussain Y, Alam W, Ullah H, Dacrema M, Daglia M, Khan H. Antimicrobial potential of curcumin: therapeutic potential and challenges to clinical applications. Antibiotics (Basel). 2022 Feb 28;11(3):322. doi: 10.3390/antibiotics11030322, PMID 35326785.
Hossain S, Islam A, Tasnim F, Hossen F, E-Zahan K, Asraf A. Antimicrobial antioxidant and cytotoxicity study of Cu(II), Zn(II), Ni(II), and Zr(IV) complexes containing O, N donor Schiff base ligand. Int J Chem Res. 2024 Oct 1;8(4):1-11.
Padalkar R, Madgulkar A, Mate R, Pawar A, Shinde A, Lohakare S. Investigation of curcumin nanoparticles and D panthenol for diabetic wound healing in wistar rats: formulation statistical optimization and in-vivo evaluation. J Drug Deliv Sci Technol. 2024 Mar;93:105390. doi: 10.1016/j.jddst.2024.105390.
Rodrigues FC, Anil Kumar NV, Thakur G. Developments in the anticancer activity of structurally modified curcumin: an up-to-date review. Eur J Med Chem. 2019 Sep;177:76-104. doi: 10.1016/j.ejmech.2019.04.058, PMID 31129455.
Singh JK, Roy AK. Role of curcumin and cumin on hematological parameters of profenofos exposed mice (Mus musculus). International Journal of Current Pharmaceutical Review and Research. 2013;4(4):120-7.
Deshkar S, Satpute A. Formulation and optimization of curcumin solid dispersion pellets for improved solubility. Int J App Pharm. 2019;12(2):36-46. doi: 10.22159/ijap.2020v12i2.34846.
Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm. 2007 Dec;4(6):807-18. doi: 10.1021/mp700113r, PMID 17999464.
Heger M, Van Golen RF, Broekgaarden M, Michel MC. The molecular basis for the pharmacokinetics and pharmacodynamics of curcumin and its metabolites in relation to cancer. Pharmacol Rev. 2014 Jan;66(1):222-307. doi: 10.1124/pr.110.004044, PMID 24368738.
Pan MH, Huang TM, Lin JK. Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metab Dispos. 1999 Apr;27(4):486-94. doi: 10.1016/S0090-9556(24)15211-7, PMID 10101144.
Ireson C, Orr S, Jones DJ, Verschoyle R, Lim CK, Luo JL. Characterization of metabolites of the chemopreventive agent curcumin in human and rat hepatocytes and in the rat in vivo and evaluation of their ability to inhibit phorbol ester-induced prostaglandin E2 production. Cancer Res. 2001 Feb 1;61(3):1058-64. PMID 11221833.
Ireson CR, Jones DJ, Orr S, Coughtrie MW, Boocock DJ, Williams ML. Metabolism of the cancer chemopreventive agent curcumin in human and rat intestine. Cancer Epidemiol Biomarkers Prev. 2002 Jan;11(1):105-11. PMID 11815407.
Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. 1998 May;64(4):353-6. doi: 10.1055/s-2006-957450, PMID 9619120.
Cheng AL, Hsu CH, Lin JK, Hsu MM, HO YF, Shen TS. Phase I clinical trial of curcumin a chemopreventive agent in patients with high risk or pre-malignant lesions. Anticancer Res. 2001;21(4B):2895-900. PMID 11712783.
Lao CD, Ruffin MT, Normolle D, Heath DD, Murray SI, Bailey JM. Dose escalation of a curcuminoid formulation. BMC Complement Altern Med. 2006 Mar 17;6:10. doi: 10.1186/1472-6882-6-10, PMID 16545122.
Sharma RA, MC Lelland HR, Hill KA, Ireson CR, Euden SA, Manson MM. Pharmacodynamic and pharmacokinetic study of oral curcuma extract in patients with colorectal cancer. Clin Cancer Res. 2001 Jul;7(7):1894-900. PMID 11448902.
Sharma RA, Euden SA, Platton SL, Cooke DN, Shafayat A, Hewitt HR. Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin Cancer Res. 2004 Oct 15;10(20):6847-54. doi: 10.1158/1078-0432.CCR-04-0744, PMID 15501961.
Garcea G, Berry DP, Jones DJ, Singh R, Dennison AR, Farmer PB. Consumption of the putative chemopreventive agent curcumin by cancer patients: assessment of curcumin levels in the colorectum and their pharmacodynamic consequences. Cancer Epidemiol Biomarkers Prev. 2005 Jan;14(1):120-5. doi: 10.1158/1055-9965.120.14.1, PMID 15668484.
Farghadani R, Naidu R. Curcumin: modulator of key molecular signaling pathways in hormone independent breast cancer. Cancers. 2021 Jul;13(14):3427. doi: 10.3390/cancers13143427, PMID 34298639.
Meybodi SM, Rezaei P, Faraji N, Jamehbozorg K, Ashna S, Shokri F. Curcumin and its novel formulations for the treatment of hepatocellular carcinoma: new trends and future perspectives in cancer therapy. J Funct Foods. 2023 Sep;108:105705. doi: 10.1016/j.jff.2023.105705.
Nocito MC, DE Luca A, Prestia F, Avena P, LA Padula D, Zavaglia L. Antitumoral activities of curcumin and recent advances to improve its oral bioavailability. Biomedicines. 2021 Oct;9(10):1476. doi: 10.3390/biomedicines9101476, PMID 34680593.
Wang X, Tian Y, Lin H, Cao X, Zhang Z. Curcumin induces apoptosis in human hepatocellular carcinoma cells by decreasing the expression of STAT3/VEGF/HIF-1α signaling. Open Life Sci. 2023 Jun 14;18(1):20220618. doi: 10.1515/biol-2022-0618, PMID 37333486.
Wang JB, QI LL, Zheng SD, WU TX. Curcumin induces apoptosis through the mitochondria mediated apoptotic pathway in HT-29 cells. J Zhejiang Univ Sci B. 2009 Feb;10(2):93-102. doi: 10.1631/jzus.B0820238, PMID 19235267.
Talib WH, Al Hadid SA, Ali MB, Al Yasari IH, Ali MR. Role of curcumin in regulating p53 in breast cancer: an overview of the mechanism of action. Breast Cancer (Dove Med Press). 2018 Nov 29;10:207-17. doi: 10.2147/BCTT.S167812, PMID 30568488.
Wang TY, Chen JX. Effects of curcumin on vessel formation insight into the pro and antiangiogenesis of curcumin. Evid Based Complement Alternat Med. 2019 Jun 19;2019:1390795. doi: 10.1155/2019/1390795, PMID 31320911.
Bhandarkar SS, Arbiser JL. Curcumin as an inhibitor of angiogenesis. Adv Exp Med Biol. 2007;595:185-95. doi: 10.1007/978-0-387-46401-5_7, PMID 17569211.
Buhrmann C, Mobasheri A, Busch F, Aldinger C, Stahlmann R, Montaseri A. Curcumin modulates nuclear factor κB (NF-κB) mediated inflammation in human tenocytes in vitro. J Biol Chem. 2011 Aug 12;286(32):28556-66. doi: 10.1074/jbc.M111.256180, PMID 21669872.
Wilken R, Veena MS, Wang MB, Srivatsan ES. Curcumin: a review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma. Mol Cancer. 2011 Feb 7;10(1):12. doi: 10.1186/1476-4598-10-12, PMID 21299897.
Ohnishi Y, Sakamoto T, Zhengguang L, Yasui H, Hamada H, Kubo H. Curcumin inhibits epithelial mesenchymal transition in oral cancer cells via c-Met blockade. Oncol Lett. 2020 Jun;19(6):4177-82. doi: 10.3892/ol.2020.11523, PMID 32391111.
Gallardo M, Calaf GM. Curcumin inhibits invasive capabilities through epithelial mesenchymal transition in breast cancer cell lines. Int J Oncol. 2016 Sep 1;49(3):1019-27. doi: 10.3892/ijo.2016.3598, PMID 27573203.
Kumar D, Kumar M, Saravanan C, Singh SK. Curcumin: a potential candidate for matrix metalloproteinase inhibitors. Expert Opin Ther Targets. 2012 Oct 1;16(10):959-72. doi: 10.1517/14728222.2012.710603, PMID 22913284.
Jakubczyk K, Drużga A, Katarzyna J, Skonieczna Zydecka K. Antioxidant potential of curcumin a meta-analysis of randomized clinical trials. Antioxidants (Basel). 2020 Nov;9(11):1092. doi: 10.3390/antiox9111092, PMID 33172016.
Sathyabhama M, Priya Dharshini LC, Karthikeyan A, Kalaiselvi S, Min T. The credible role of curcumin in oxidative stress mediated mitochondrial dysfunction in mammals. Biomolecules. 2022 Oct;12(10):1405. doi: 10.3390/biom12101405, PMID 36291614.
HU P, KE C, Guo X, Ren P, Tong Y, Luo S. Both glypican-3/Wnt/β-catenin signaling pathway and autophagy contributed to the inhibitory effect of curcumin on hepatocellular carcinoma. Dig Liver Dis. 2019 Jan;51(1):120-6. doi: 10.1016/j.dld.2018.06.012, PMID 30001951.
Liang J, Zhou F, Xiong X, Zhang X, LI S, LI X. Enhancing the retrograde axonal transport by curcumin promotes autophagic flux in N2a/APP695swe cells. Aging (Albany, NY). 2019 Sep 6;11(17):7036-50. doi: 10.18632/aging.102235, PMID 31488728.
Hassan FU, Rehman MS, Khan MS, Ali MA, Javed A, Nawaz A. Curcumin as an alternative epigenetic modulator: mechanism of action and potential effects. Front Genet. 2019 Jun 4;10:514. doi: 10.3389/fgene.2019.00514, PMID 31214247.
Ming T, Tao Q, Tang S, Zhao H, Yang H, Liu M. Curcumin: an epigenetic regulator and its application in cancer. Biomed Pharmacother. 2022 Dec 1;156:113956. doi: 10.1016/j.biopha.2022.113956, PMID 36411666.
BioRender.com. Available from: https://app.biorender. [Last accessed on 20 Feb 2025].
Kaur K, Kulkarni YA, Wairkar S. Exploring the potential of quercetin in alzheimers disease: pharmacodynamics pharmacokinetics and nanodelivery systems. Brain Res. 2024;1834:148905. doi: 10.1016/j.brainres.2024.148905, PMID 38565372.
Wang Y, Ding R, Zhang Z, Zhong C, Wang J, Wang M. Curcumin loaded liposomes with the hepatic and lysosomal dual targeted effects for therapy of hepatocellular carcinoma. Int J Pharm. 2021 Jun 1;602:120628. doi: 10.1016/j.ijpharm.2021.120628, PMID 33892061.
Greil R, Greil Ressler S, Weiss L, Schonlieb C, Magnes T, Radl B. A phase 1 dose-escalation study on the safety tolerability and activity of liposomal curcumin (LipocurcTM) in patients with locally advanced or metastatic cancer. Cancer Chemotherpharmacol. 2018;82(4):695-706.
Wei Y, LI K, Zhao W, HE Y, Shen H, Yuan J. The effects of a novel curcumin derivative loaded long circulating solid lipid nanoparticle on the MHCC-97H liver cancer cells and pharmacokinetic behavior. Int J Nanomedicine. 2022 May 17;17:2225-41. doi: 10.2147/IJN.S363237, PMID 35607705.
Shah J, Patel S, Bhairy S, Hirlekar R. Formulation optimization characterization and in vitro anti-cancer activity of curcumin loaded nanostructured lipid carriers. Int J Curr Pharm Sci. 2022;14(1):31-43. doi: 10.22159/ijcpr.2022v14i1.44110.
Wang F, YE X, Zhai D, Dai W, WU Y, Chen J. Curcumin loaded nanostructured lipid carrier induced apoptosis in human HepG2 cells through activation of the DR5/caspase mediated extrinsic apoptosis pathway. Acta Pharm. 2020;70(2):227-37. doi: 10.2478/acph-2020-0003, PMID 31955141.
Chu Y, LI D, Luo YF, HE XJ, Jiang MY. Preparation and in vitro evaluation of glycyrrhetinic acid modified curcumin loaded nanostructured lipid carriers. Molecules. 2014;19(2):2445-57. doi: 10.3390/molecules19022445, PMID 24566313.
Guo P, PI C, Zhao S, FU S, Yang H, Zheng X. Oral co-delivery nanoemulsion of 5-fluorouracil and curcumin for synergistic effects against liver cancer. Expert Opin Drug Deliv. 2020;17(10):1473-84. doi: 10.1080/17425247.2020.1796629, PMID 32749895.
Al CA, PS S, ND DR C. Design and evaluation of capecitabine resealed erythrocytes by preswell and dilution techniques. Int J Biol Pharm Allied Sci. 2021;10(12).
Salve P, Doijad R, Chivate N. Resealed erythrocytes: a promising approach to enhance efficacy of anticancer drugs. IND DRU. 2020;57(3):9-20. doi: 10.53879/id.57.03.11645.
Xie X, Wang H, Williams GR, Yang Y, Zheng Y, WU J. Erythrocyte membrane cloaked curcumin loaded nanoparticles for enhanced chemotherapy. Pharmaceutics. 2019;11(9):429. doi: 10.3390/pharmaceutics11090429, PMID 31450749.
Kong ZL, Kuo HP, Johnson A, WU LC, Chang KL. Curcumin loaded mesoporous silica nanoparticles markedly enhanced cytotoxicity in hepatocellular carcinoma cells. Int J Mol Sci. 2019;20(12):2918. doi: 10.3390/ijms20122918, PMID 31207976.
Darwesh R, Elbialy NS. Iron oxide nanoparticles conjugated curcumin to promote high therapeutic efficacy of curcumin against hepatocellular carcinoma. Inorg Chem Commun. 2021;126:108482. doi: 10.1016/j.inoche.2021.108482.
Alshawwa SZ, Kassem AA, Farid RM, Mostafa SK, Labib GS. Nanocarrier drug delivery systems: characterization limitations future perspectives and implementation of artificial intelligence. Pharmaceutics. 2022;14(4):883. doi: 10.3390/pharmaceutics14040883, PMID 35456717.
Desai N. Challenges in development of nanoparticle based therapeutics. AAPS J. 2012;14(2):282-95. doi: 10.1208/s12248-012-9339-4, PMID 22407288.
Pingale P, Kendre P, Pardeshi K, Rajput A. An emerging era in manufacturing of drug delivery systems: nanofabrication techniques. Heliyon. 2023;9(3):e14247. doi: 10.1016/j.heliyon.2023.e14247, PMID 36938476.
Sedighi M, Mahmoudi Z, Abbaszadeh S, Eskandari MR, Saeinasab M, Sefat F. Nanomedicines for hepatocellular carcinoma therapy: challenges and clinical applications. Mater Today Commun. 2023 Mar;34:105242. doi: 10.1016/j.mtcomm.2022.105242.
Hegde M, Girisa S, Bharathwaj Chetty B, Vishwa R, Kunnumakkara AB. Curcumin formulations for better bioavailability: what we learned from clinical trials thus far? ACS Omega. 2023;8(12):10713-46. doi: 10.1021/acsomega.2c07326, PMID 37008131.
Vareed SK, Kakarala M, Ruffin MT, Crowell JA, Normolle DP, Djuric Z. Pharmacokinetics of curcumin conjugate metabolites in healthy human subjects. Cancer Epidemiol Biomarkers Prev. 2008;17(6):1411-7. doi: 10.1158/1055-9965.EPI-07-2693, PMID 18559556.
LI C, Naeem A, Shen J, Zha W, Zeng Q, Zhang P. Advances in the pharmaceutical research of curcumin for oral administration. Open Chem. 2023;21(1). doi: 10.1515/chem-2023-0171.
Sai Y. Biochemical and molecular pharmacological aspects of transporters as determinants of drug disposition. Drug Metab Pharmacokinet. 2005;20(2):91-9. doi: 10.2133/dmpk.20.91, PMID 15855719.
Din FU, Aman W, Ullah I, Qureshi OS, Mustapha O, Shafique S. Effective use of nanocarriers as drug delivery systems for the treatment of selected tumors. Int J Nanomedicine. 2017 Oct 5;12:7291-309. doi: 10.2147/IJN.S146315, PMID 29042776.
Ayan AK, Yenilmez A, Eroglu H. Evaluation of radiolabeled curcumin loaded solid lipid nanoparticles usage as an imaging agent in liver spleen scintigraphy. Mater Sci Eng C Mater Biol Appl. 2017 Jun 1;75:663-70. doi: 10.1016/j.msec.2017.02.114, PMID 28415513.
Sun Q, LV M, LI Y. Nanotechnology based drug delivery systems for curcumin and its derivatives in the treatment of cardiovascular diseases. J Funct Foods. 2024 Nov;122:106476. doi: 10.1016/j.jff.2024.106476.
Panda SS, Thangaraju M, Lokeshwar BL. Hybrid curcumin conjugates and methods of use thereof. US20220152211A1; 2022.
Kim DH, Kwak K. Immuno ablation treatment for solid tumors. WO2023225578A3; 2024.
Guo Yongcheng. A composition with the effect of inhibiting the proliferation of liver cancer cells and its application. CN108272780A; 2018.
LI SD, Zhang W, Chao PH, Boettger R. Phospholipid free small unilamellar vesicles (pfsuvs) for drug delivery. WO2020087175A1; 2020.
Neven P, Serteyn D, Jacques D (Deceased), Kiss R, Mathieu V, Cataldo D, Rocks N. Water soluble curcumin compositions for use in anticancer and anti-inflammatory therapy. WO2009144220A1; 2009.
Aggarwal B. Selective inhibitors of STAT-3 activation and uses thereof. US20050049299A1; 2005.
Sahin F, Ulu ZO, Bolat ZB, Degirmenci NS. An anticancer formulation comprising sodium pentaborate, curcumin, and piperine for use in the treatment of hepatocellular carcinoma. WO2023191746A1; 2023.
Published
How to Cite
Issue
Section
Copyright (c) 2025 RESHMA T. MATE, ANURADHA N. CHIVATE, NAMDEO R. JADHAV, NIRANJAN D. CHIVATE
This work is licensed under a Creative Commons Attribution 4.0 International License.
