Abstract
Background: Natural phytochemicals and their derivatives have been used in medicine since prehistoric times. Natural phytochemicals have potential uses against various disorders, including cancers. However, due to low bioavailability, their success in clinical trials has not been reproduced. Nanotechnology has played a vital role in providing new directions for diagnosis, prevention, and treatment of different disorders, and of cancer in particular. Nanotechnology has demonstrated the capability to deliver conventional natural products with poor solubility or a short half-life to target specific sites in the body and regulate the release of drugs. Among the natural products, the phytoalexin resveratrol has demonstrated therapeutic effects, including antioxidant, antiinflammatory, and anti-proliferative effects, as well as the potential to inhibit the initiation and promotion of cancer. However, low water solubility and extensive first-pass metabolism lead to poor bioavailability of resveratrol, hindering its potential. Conventional dosage forms of resveratrol, such as tablets, capsules, dry powder, and injections, have met with limited success. Nanoformulations are now being investigated to improve the pharmacokinetic characteristics, as well as to enhance the bioavailability and targetability of resveratrol.
Objectives: This review details the therapeutic effectiveness, mode of action, and pharmacokinetic limitations of resveratrol, as well as discusses the successes and challenges of resveratrol nanoformulations. Modern nanotechnology techniques to enhance the encapsulation of resveratrol within nanoparticles and thereby enhance its therapeutic effects are emphasized. Conclusion: To date, no resveratrol-based nanosystems are in clinical use, and this review would provide a new direction for further investigations on innovative nanodevices that could consolidate the anticancer potential of resveratrol.Keywords: Cancer, phytochemicals, resveratrol, nanotechnology, solid lipid nanoparticles, liposomes, cyclodextrins, polymeric nanoparticles.
[http://dx.doi.org/10.2174/138920008785821657] [PMID: 18781909]
[http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.v20.i5.20]
[http://dx.doi.org/10.2174/1568009023333836] [PMID: 12188908]
[http://dx.doi.org/10.1111/j.1349-7006.2011.01941.x] [PMID: 21447010]
[http://dx.doi.org/10.1038/nnano.2007.387] [PMID: 18654426]
[http://dx.doi.org/10.1007/s10570-016-1053-4]
[http://dx.doi.org/10.1016/j.molliq.2016.12.061]
[http://dx.doi.org/10.1038/s41598-018-24311-4] [PMID: 29674721]
[http://dx.doi.org/10.1038/s41598-017-16815-2] [PMID: 29209040]
[http://dx.doi.org/10.1016/j.carbpol.2018.03.029] [PMID: 29691016]
[http://dx.doi.org/10.1016/j.chemosphere.2017.08.118] [PMID: 28917211]
[http://dx.doi.org/10.1016/j.carbpol.2017.05.074] [PMID: 28732913]
[http://dx.doi.org/10.1016/j.ijbiomac.2018.01.092] [PMID: 29355628]
[http://dx.doi.org/10.1007/s00289-016-1788-y]
[http://dx.doi.org/10.1016/j.ijbiomac.2017.12.022] [PMID: 29222019]
[http://dx.doi.org/10.1016/j.apsusc.2016.06.133]
[http://dx.doi.org/10.1016/j.jallcom.2017.09.124]
[http://dx.doi.org/10.1016/j.carbpol.2016.09.078] [PMID: 27987930]
[http://dx.doi.org/10.5004/dwt.2019.24054]
[http://dx.doi.org/10.1016/j.polymertesting.2019.105983]
[http://dx.doi.org/10.1146/annurev.bioeng.9.060906.152025] [PMID: 17439359]
[PMID: 11999713]
[http://dx.doi.org/10.5004/dwt.2018.23230]
[http://dx.doi.org/10.2174/1872210510666160429145704] [PMID: 27136927]
[http://dx.doi.org/10.1016/j.carbpol.2016.04.042] [PMID: 27185126]
[http://dx.doi.org/10.1016/j.envpol.2016.07.046] [PMID: 27481647]
[http://dx.doi.org/10.1007/s10570-016-0919-9]
[http://dx.doi.org/10.1016/j.ijbiomac.2017.05.157] [PMID: 28571736]
[http://dx.doi.org/10.1016/j.ijbiomac.2015.08.060] [PMID: 26321421]
[http://dx.doi.org/10.1016/j.jallcom.2017.01.306]
[http://dx.doi.org/10.1016/j.ijbiomac.2017.04.062] [PMID: 28428128]
[http://dx.doi.org/10.2174/1872210510666160429145339] [PMID: 27136929]
[http://dx.doi.org/10.1016/j.ijbiomac.2016.06.018] [PMID: 27287771]
[http://dx.doi.org/10.1016/j.ijbiomac.2016.03.026] [PMID: 26993528]
[http://dx.doi.org/10.1039/C6RA21626A]
[http://dx.doi.org/10.2174/1872210510666160429144916] [PMID: 27136931]
[http://dx.doi.org/10.1016/j.ijbiomac.2019.03.205] [PMID: 30928377]
[http://dx.doi.org/10.1016/j.ijbiomac.2019.05.057] [PMID: 31145951]
[http://dx.doi.org/10.1038/nnano.2007.88] [PMID: 18654260]
[http://dx.doi.org/10.1038/nrc1566] [PMID: 15738981]
[http://dx.doi.org/10.3322/CA.2007.0003] [PMID: 18227410]
[http://dx.doi.org/10.1002/cncr.22035] [PMID: 16795065]
[http://dx.doi.org/10.1002/wnan.6] [PMID: 20049796]
[http://dx.doi.org/10.1158/0008-5472.CAN-08-3978] [PMID: 19223530]
[http://dx.doi.org/10.1007/s11095-010-0087-9] [PMID: 20221894]
[PMID: 24531078]
[http://dx.doi.org/10.1007/s726-002-8197-9] [PMID: 12025870]
[http://dx.doi.org/10.1023/B:HIJO.0000032361.98815.bb] [PMID: 15339049]
[http://dx.doi.org/10.2174/092986709787909578] [PMID: 19355899]
[http://dx.doi.org/10.1038/nrc3017] [PMID: 21326325]
[http://dx.doi.org/10.1517/14656560802560153] [PMID: 19236194]
[http://dx.doi.org/10.1016/j.canlet.2007.03.005] [PMID: 17448598]
[http://dx.doi.org/10.1007/s00018-008-7452-4] [PMID: 18324353]
[http://dx.doi.org/10.1016/j.jaad.2007.12.035] [PMID: 18249471]
[http://dx.doi.org/10.4149/neo_2011_02_118] [PMID: 21275460]
[http://dx.doi.org/10.1158/1535-7163.MCT-08-0905] [PMID: 19372569]
[http://dx.doi.org/10.14348/molcells.2014.0212] [PMID: 25431425]
[PMID: 12680238]
[http://dx.doi.org/10.1016/j.ejps.2009.02.019] [PMID: 19491009]
[http://dx.doi.org/10.1166/jbn.2009.1038] [PMID: 20201417]
[http://dx.doi.org/10.1016/j.jcis.2010.05.022] [PMID: 20627257]
[http://dx.doi.org/10.3892/ijo.32.5.1119] [PMID: 18425340]
[http://dx.doi.org/10.1124/mol.109.054551] [PMID: 19395473]
[http://dx.doi.org/10.18632/oncotarget.19164] [PMID: 29029547]
[PMID: 19846921]
[http://dx.doi.org/10.1007/s10555-010-9235-2] [PMID: 20737283]
[http://dx.doi.org/10.1177/030089161009600225] [PMID: 20572596]
[http://dx.doi.org/10.1111/j.1582-4934.2008.00539.x] [PMID: 19473291]
[http://dx.doi.org/10.1016/S0168-3659(02)00212-2] [PMID: 12363453]
[http://dx.doi.org/10.2174/0929867043455909] [PMID: 14965222]
[http://dx.doi.org/10.1002/ijc.20405] [PMID: 15352049]
[http://dx.doi.org/10.1080/07315724.2010.10719814] [PMID: 20595643]
[http://dx.doi.org/10.1080/07315724.2006.10719518] [PMID: 16582024]
[http://dx.doi.org/10.1021/nn900451a] [PMID: 19534472]
[PMID: 19618731]
[PMID: 15517885]
[http://dx.doi.org/10.1016/S0027-5107(02)00330-5] [PMID: 12628512]
[http://dx.doi.org/10.2174/138920009789375423] [PMID: 19702538]
[http://dx.doi.org/10.3390/molecules171012393] [PMID: 23090020]
[http://dx.doi.org/10.18632/oncotarget.17855] [PMID: 28915620]
[http://dx.doi.org/10.1016/j.yexcr.2018.05.018] [PMID: 29787735]
[http://dx.doi.org/10.1167/iovs.07-1233] [PMID: 18385041]
[http://dx.doi.org/10.1016/j.taap.2012.05.023] [PMID: 22687606]
[http://dx.doi.org/10.1080/19768354.2015.1101398]
[http://dx.doi.org/10.1111/j.1749-6632.2010.05852.x] [PMID: 21261654]
[http://dx.doi.org/10.1186/1750-2187-2-7] [PMID: 17718901]
[http://dx.doi.org/10.1007/s11010-007-9510-x] [PMID: 17636462]
[PMID: 25667456]
[http://dx.doi.org/10.3892/ijo.2015.3124] [PMID: 26314326]
[PMID: 26189302]
[http://dx.doi.org/10.1089/jmf.2010.1126] [PMID: 20946021]
[http://dx.doi.org/10.1016/S0024-3205(02)02177-X] [PMID: 12409142]
[http://dx.doi.org/10.1006/bbrc.2001.5819] [PMID: 11676482]
[http://dx.doi.org/10.1002/mnfr.200800177] [PMID: 19194969]
[http://dx.doi.org/10.3390/ijms19092816] [PMID: 30231546]
[http://dx.doi.org/10.1155/2013/506083]
[http://dx.doi.org/10.2147/IJN.S29710] [PMID: 22605933]
[http://dx.doi.org/10.1016/j.colsurfb.2013.11.025] [PMID: 24321846]
[http://dx.doi.org/10.1007/0-306-47932-X_2]
[http://dx.doi.org/10.1016/j.drudis.2006.07.005] [PMID: 16935749]
[http://dx.doi.org/10.1016/S0065-2571(00)00013-3] [PMID: 11384745]
[http://dx.doi.org/10.1016/S0169-409X(00)00134-4] [PMID: 11259839]
[http://dx.doi.org/10.1016/j.ejpb.2008.11.010] [PMID: 19070661]
[PMID: 2946403]
[http://dx.doi.org/10.1007/978-3-642-00477-3_4]
[http://dx.doi.org/10.1016/j.ijpharm.2009.10.011] [PMID: 19833178]
[http://dx.doi.org/10.1080/713817583] [PMID: 11811751]
[http://dx.doi.org/10.1080/10611860701794353] [PMID: 18274932]
[http://dx.doi.org/10.1080/01932691.2010.548274]
[PMID: 23326193]
[http://dx.doi.org/10.1016/j.ijpharm.2014.08.003] [PMID: 25102112]
[http://dx.doi.org/10.1016/j.addr.2012.09.037] [PMID: 23036225]
[http://dx.doi.org/10.1016/j.ijpharm.2013.01.050] [PMID: 23380621]
[http://dx.doi.org/10.2174/092986710790416290] [PMID: 20015030]
[http://dx.doi.org/10.1080/08982100500364131] [PMID: 16393907]
[http://dx.doi.org/10.1177/0192623307310960] [PMID: 18337218]
[http://dx.doi.org/10.1073/pnas.93.21.11443] [PMID: 8876154]
[http://dx.doi.org/10.1016/S0378-5173(97)00135-X]
[http://dx.doi.org/10.1016/j.ijpharm.2011.01.056] [PMID: 21291975]
[http://dx.doi.org/10.1111/j.1751-1097.2012.01147.x] [PMID: 22443373]
[http://dx.doi.org/10.1016/j.ifset.2013.03.006]
[http://dx.doi.org/10.1016/j.ejpb.2009.06.006] [PMID: 19527785]
[http://dx.doi.org/10.1021/ar200113c] [PMID: 22074988]
[http://dx.doi.org/10.1016/j.ijpharm.2008.07.024] [PMID: 18718515]
[http://dx.doi.org/10.2217/nnm.13.118] [PMID: 23914966]
[http://dx.doi.org/10.1016/j.yexmp.2008.12.004] [PMID: 19186176]
[http://dx.doi.org/10.3109/03639045.2011.602410] [PMID: 21851312]
[http://dx.doi.org/10.1248/cpb.52.641] [PMID: 15133226]
[http://dx.doi.org/10.1371/journal.pone.0041438] [PMID: 22936976]
[http://dx.doi.org/10.1002/app.37701]
[http://dx.doi.org/10.1002/ijc.11108] [PMID: 12712451]
[http://dx.doi.org/10.1093/gerona/glu029] [PMID: 24642904]
[http://dx.doi.org/10.1007/s10549-013-2667-y] [PMID: 23959397]
[http://dx.doi.org/10.1016/j.biomaterials.2011.04.029] [PMID: 21550109]
[http://dx.doi.org/10.4103/0975-7406.67003] [PMID: 21814436]
[http://dx.doi.org/10.1007/s10847-011-0058-8]
[http://dx.doi.org/10.1002/9781118140291]
[http://dx.doi.org/10.1016/j.foodchem.2013.08.034] [PMID: 24128457]
[http://dx.doi.org/10.1517/17425247.2014.890588] [PMID: 24661109]
[http://dx.doi.org/10.1021/mp400342f] [PMID: 23968375]
[http://dx.doi.org/10.1016/j.ejphar.2013.09.034] [PMID: 24070814]
[http://dx.doi.org/10.1166/jbn.2014.1897] [PMID: 25016653]
[http://dx.doi.org/10.1016/j.ijpharm.2009.03.021] [PMID: 19481694]
[http://dx.doi.org/10.1039/b514858h] [PMID: 17057836]
[http://dx.doi.org/10.1517/17425240903380446] [PMID: 20017660]