Abstract
Cancer accounts for the second major cause of death globally. Conventional cancer therapies lead to systemic toxicity that forbids their long term application. Besides, tumor resistance and recurrence have been observed in the majority of cases. Thus, the development of such therapy, which will pose minimum side effects, is the need of the hour. Curcumin or diferuloylmethane (CUR) is a natural polyphenol bioactive (obtained from Curcuma longa) which possesses anti-cancer and chemo-preventive activity. It acts by modulating various components of signaling cascades that are involved in cancer cell proliferation, invasion, and apoptosis process. It interacts with the adaptive and innate immune systems of our body and causes tumor regression. This may be the reason behind the attainment of in vivo anti-tumor activity at a very low concentration. Its ease of availability, safety profile, low cost, and multifaceted role in cancer prevention and treatment has made it a promising agent for chemoprevention of many cancers. Regardless of the phenomenal properties, its clinical utility is haltered due to its low aqueous solubility, poor bioavailability, rapid metabolism, and low cellular uptake. In the last few years, a variety of novel drug carriers have been fabricated to enhance the bioavailability and pharmacokinetic profile of CUR to attain better targeting of cancer. In this review, the recent developments in the arena of nanoformulations, like liposomes, polymeric NPs, solid lipid NPs (SNPs), polymeric micelles, nanoemulsions, microspheres, nanogels, etc. in anticancer therapy have been discussed along with a brief overview of the molecular targets for CUR in cancer therapy and role of CUR in cancer immunotherapy.
Keywords: Curcumin, cancer therapy, liposomes, nano-formulations, drug delivery, solubility.
[http://dx.doi.org/10.3322/caac.21551] [PMID: 30620402]
[PMID: 31701486]
[http://dx.doi.org/10.1038/nature03095] [PMID: 15549090]
[PMID: 9537241]
[http://dx.doi.org/10.1016/j.addr.2004.02.014] [PMID: 15350294]
[http://dx.doi.org/10.2174/1568009043332989] [PMID: 15180497]
[http://dx.doi.org/10.1038/nrc2817] [PMID: 20300106]
[http://dx.doi.org/10.1038/nrd1984] [PMID: 16518375]
[http://dx.doi.org/10.1038/nrc706] [PMID: 11902585]
[http://dx.doi.org/10.1007/978-1-60761-416-6_4]
[http://dx.doi.org/10.1111/j.1365-2184.2012.00845.x] [PMID: 23030059]
[http://dx.doi.org/10.1016/j.ejca.2005.07.034] [PMID: 16376541]
[http://dx.doi.org/10.2174/1570163811666140616153436] [PMID: 24934264]
[http://dx.doi.org/10.1517/17425247.2014.916686] [PMID: 24857605]
[http://dx.doi.org/10.1002/jcp.26055] [PMID: 28617957]
[http://dx.doi.org/10.3109/1061186X.2015.1055570] [PMID: 26066739]
[http://dx.doi.org/10.4161/cbt.11.5.14810] [PMID: 21263231]
[http://dx.doi.org/10.1186/1477-3155-5-3] [PMID: 17439648]
[http://dx.doi.org/10.1016/j.biocel.2008.06.010] [PMID: 18662800]
[http://dx.doi.org/10.3390/molecules16064567] [PMID: 21642934]
[http://dx.doi.org/10.1186/1476-4598-10-12] [PMID: 21299897]
[http://dx.doi.org/10.2174/092986710790149738] [PMID: 20214562]
[http://dx.doi.org/10.1208/s12248-016-0003-2] [PMID: 27783266]
[http://dx.doi.org/10.1158/1940-6207.CAPR-10-0006] [PMID: 21546540]
[http://dx.doi.org/10.1073/pnas.0905487106] [PMID: 19564622]
[http://dx.doi.org/10.1080/03639040601050163] [PMID: 17654025]
[http://dx.doi.org/10.2174/1389450119666180131105822] [PMID: 29384060]
[http://dx.doi.org/10.1007/s11095-006-9223-y] [PMID: 17385025]
[http://dx.doi.org/10.1016/j.yexmp.2008.12.004] [PMID: 19186176]
[PMID: 24399876]
[http://dx.doi.org/10.1208/aapsj080352] [PMID: 17025261]
[http://dx.doi.org/10.3390/ijms20081808] [PMID: 31013694]
[http://dx.doi.org/10.1039/c3ra46396f]
[http://dx.doi.org/10.1002/biof.1065] [PMID: 23303697]
[http://dx.doi.org/10.1002/jcb.24612] [PMID: 23794119]
[PMID: 12297018]
[http://dx.doi.org/10.1074/jbc.M606003200] [PMID: 17148446]
[http://dx.doi.org/10.2174/138945011794815356] [PMID: 20955148]
[http://dx.doi.org/10.1002/ardp.200900319] [PMID: 20726007]
[http://dx.doi.org/10.1007/BF02673865] [PMID: 11732181]
[http://dx.doi.org/10.1158/1940-6207.CAPR-13-0387] [PMID: 24550143]
[http://dx.doi.org/10.4161/cc.6.23.4951] [PMID: 18156803]
[http://dx.doi.org/10.1186/1471-2407-1-1] [PMID: 11231886]
[http://dx.doi.org/10.1254/jphs.12149FP] [PMID: 23603894]
[http://dx.doi.org/10.3748/wjg.v24.i39.4428] [PMID: 30357011]
[http://dx.doi.org/10.1038/onc.2016.304] [PMID: 27617575]
[http://dx.doi.org/10.3389/fphar.2017.00877] [PMID: 29225578]
[http://dx.doi.org/10.1371/journal.pone.0120045] [PMID: 25786122]
[http://dx.doi.org/10.2174/092986711795843218] [PMID: 21568920]
[http://dx.doi.org/10.1016/j.bcp.2006.07.029] [PMID: 16959222]
[http://dx.doi.org/10.3892/mmr_00000005] [PMID: 21479462]
[http://dx.doi.org/10.1371/journal.pone.0085796] [PMID: 24465712]
[http://dx.doi.org/10.1093/carcin/bgs312] [PMID: 23042094]
[http://dx.doi.org/10.1158/1940-6207.CAPR-12-0410] [PMID: 23466484]
[http://dx.doi.org/10.1016/j.jddst.2020.101549]
[http://dx.doi.org/10.1016/j.drudis.2011.09.009] [PMID: 21959306]
[http://dx.doi.org/10.1080/15384047.2018.1550567] [PMID: 30621501]
[http://dx.doi.org/10.1021/acsami.7b02863] [PMID: 28489348]
[http://dx.doi.org/10.1155/2013/705265]
[http://dx.doi.org/10.1007/s13346-018-00598-8] [PMID: 30421392]
[http://dx.doi.org/10.2147/IJN.S188971] [PMID: 30880980]
[http://dx.doi.org/10.3109/08982104.2011.627514] [PMID: 22372871]
[http://dx.doi.org/10.1016/j.ijpharm.2018.05.007] [PMID: 29730175]
[http://dx.doi.org/10.1002/mnfr.201000310] [PMID: 20938993]
[http://dx.doi.org/10.1039/c3fo60180c] [PMID: 23921424]
[http://dx.doi.org/10.3390/molecules23071578] [PMID: 29966245]
[http://dx.doi.org/10.1208/s12249-017-0772-7] [PMID: 28397161]
[http://dx.doi.org/10.1016/j.actbio.2017.04.029] [PMID: 28455219]
[http://dx.doi.org/10.1021/nn103336a] [PMID: 21557611]
[http://dx.doi.org/10.1016/j.foodchem.2011.11.039] [PMID: 22868161]
[http://dx.doi.org/10.1007/s11596-017-1742-8] [PMID: 28585133]
[http://dx.doi.org/10.1155/2018/4057959]
[http://dx.doi.org/10.1039/C8NR06173D] [PMID: 30484463]
[http://dx.doi.org/10.1016/S0731-7085(02)00460-0] [PMID: 12408911]
[http://dx.doi.org/10.1080/03639045.2016.1239732] [PMID: 27648633]
[http://dx.doi.org/10.1021/mp800240j] [PMID: 19278222]
[http://dx.doi.org/10.1517/14712598.4.1.35] [PMID: 14680467]
[http://dx.doi.org/10.1007/3-540-45734-8_3]
[http://dx.doi.org/10.1016/j.ijpharm.2019.118644] [PMID: 31465837]
[http://dx.doi.org/10.1016/j.colsurfb.2016.09.044] [PMID: 27701049]
[http://dx.doi.org/10.1016/j.msec.2018.10.071] [PMID: 30573243]
[http://dx.doi.org/10.1038/srep28373] [PMID: 27324595]
[http://dx.doi.org/10.1016/j.jconrel.2011.12.012] [PMID: 22285551]
[http://dx.doi.org/10.1016/S0169-409X(96)00401-2]
[http://dx.doi.org/10.1208/s12249-017-0906-y] [PMID: 29110292]
[http://dx.doi.org/10.1016/j.msec.2019.03.100] [PMID: 31029341]
[http://dx.doi.org/10.1080/10837450.2019.1647236] [PMID: 31340709]
[http://dx.doi.org/10.1080/03639045.2018.1562462] [PMID: 30572745]
[http://dx.doi.org/10.1016/j.phrs.2019.104353] [PMID: 31306775]
[http://dx.doi.org/10.1016/0167-4889(94)90198-8] [PMID: 7981240]
[http://dx.doi.org/10.1111/j.1365-2141.2005.05720.x] [PMID: 16173963]
[http://dx.doi.org/10.4049/jimmunol.174.12.8116] [PMID: 15944320]
[http://dx.doi.org/10.1006/clim.1999.4769] [PMID: 10527691]
[http://dx.doi.org/10.1158/1078-0432.CCR-08-1511] [PMID: 19228728]
[PMID: 9457037]
[http://dx.doi.org/10.1002/ijc.2910610607] [PMID: 7790111]
[PMID: 11406550]
[http://dx.doi.org/10.1016/S0165-2478(00)00247-9] [PMID: 10996626]
[http://dx.doi.org/10.1006/jsre.2000.5826] [PMID: 10729246]
[http://dx.doi.org/10.1186/s13008-015-0012-z] [PMID: 26464579]
[http://dx.doi.org/10.1016/j.intimp.2012.06.016] [PMID: 22749847]
[http://dx.doi.org/10.1016/j.immuni.2013.11.005] [PMID: 24315995]
[http://dx.doi.org/10.1038/cmi.2010.11] [PMID: 20305684]
[http://dx.doi.org/10.1074/jbc.M608189200] [PMID: 17392282]
[http://dx.doi.org/10.1158/0008-5472.CAN-06-2583] [PMID: 17210719]
[http://dx.doi.org/10.1016/j.intimp.2011.04.002] [PMID: 21497674]
[http://dx.doi.org/10.1007/s00018-008-7452-4] [PMID: 18324353]
[http://dx.doi.org/10.1667/RR3255.1] [PMID: 23745991]
[http://dx.doi.org/10.1053/j.gastro.2018.05.031] [PMID: 29802852]