Abstract
Oral anticancer therapy faces several drawbacks: low aqueous solubility, poor and irregular absorption from gastrointestinal sites, high first-pass metabolism, food-influenced absorption, non-targeted delivery, severe systemic and local adverse effects, etc. Enhancement of oral bioavailability could reduce the drug load and associated adverse effects. Self-emulsifying drug delivery systems (SEDDS) can enhance in-vivo solubility and drug absorption from the gastrointestinal tract, bypass liver metabolism by lymphatic absorption and inhibit efflux transport. All these phenomena ultimately result in improved oral bioavailability. Anticancer drug delivery using the SEDDS has shown promising results for bioavailability and pharmacodynamic response. A handful of research studies have produced evidence of the successful loading of anticancer agents in SEDDS-based formulations. Various potent and established chemotherapeutic agents such as docetaxel, paclitaxel, etoposide, 5 Fluorouracil, doxorubicin etc., have been successfully formulated and evaluated. Improved bioavailability and reduction of dose might be possible by SEDDS. It could be effective for low-dose drugs. But, excessive surfactant- cosurfactant concentration, lacking predictive in-vitro models and adequate IVIVC, and unavailability of toxicity data are certain challenges for future researchers. No clinical trials have been recorded with anticancer drug-loaded SEDDS. Overcoming the challenges and further progression to clinical studies are required to avail the benefits of anticancer SEDDS.
Keywords: Self-emulsifying, SEDDS, SNEDDS, anticancer, bioavailability, oral delivery.
[http://dx.doi.org/10.1016/j.jddst.2018.01.013]
[http://dx.doi.org/10.1080/10717544.2016.1214990] [PMID: 27685505]
[http://dx.doi.org/10.1016/j.drudis.2010.08.007] [PMID: 20727418]
[http://dx.doi.org/10.1016/S0378-5173(00)00614-1] [PMID: 11165081]
[http://dx.doi.org/10.4172/2157-7463.1000124]
[http://dx.doi.org/10.1208/s12249-019-1335-x] [PMID: 30815765]
[http://dx.doi.org/10.1166/jbn.2017.2385]
[http://dx.doi.org/10.1016/j.ijpharm.2018.06.005] [PMID: 29883790]
[http://dx.doi.org/10.3109/10837450.2015.1089899] [PMID: 26458371]
[http://dx.doi.org/10.1016/j.cplett.2010.01.001]
[http://dx.doi.org/10.1039/c0dt00292e] [PMID: 20593091]
[http://dx.doi.org/10.1517/14712591003586806] [PMID: 20095876]
[http://dx.doi.org/10.1038/nmeth.3891] [PMID: 27240257]
[http://dx.doi.org/10.1016/S1470-2045(13)70274-2] [PMID: 23850491]
[http://dx.doi.org/10.1016/j.juro.2016.10.101] [PMID: 28012770]
[http://dx.doi.org/10.1016/j.steroids.2019.108505] [PMID: 31568765]
[http://dx.doi.org/10.1016/j.ejca.2016.02.024] [PMID: 27084345]
[http://dx.doi.org/10.1016/j.bbacli.2015.04.001] [PMID: 26673349]
[http://dx.doi.org/10.1016/j.jconrel.2013.04.020] [PMID: 23648832]
[http://dx.doi.org/10.5772/intechopen.88412]
[http://dx.doi.org/10.1016/j.ijpharm.2015.12.054]
[http://dx.doi.org/10.1007/s11095-010-0110-1] [PMID: 20333455]
[http://dx.doi.org/10.3762/bjoc.11.22] [PMID: 25815071]
[http://dx.doi.org/10.1208/s12249-015-0370-5]
[http://dx.doi.org/10.3238/arztebl.2019.0775] [PMID: 31920193]
[http://dx.doi.org/10.4324/9780203994559-14]
[http://dx.doi.org/10.3390/pharmaceutics11030132] [PMID: 30893899]
[http://dx.doi.org/10.3390/pharmaceutics12121175] [PMID: 33276565]
[http://dx.doi.org/10.1517/17425247.2015.1060219] [PMID: 26144859]
[http://dx.doi.org/10.1111/jphp.13072] [PMID: 30784086]
[http://dx.doi.org/10.1016/j.ijpharm.2019.05.033] [PMID: 31125713]
[http://dx.doi.org/10.1016/j.ejpb.2010.06.008] [PMID: 20600890]
[http://dx.doi.org/10.1016/j.drudis.2009.07.010] [PMID: 19647803]
[http://dx.doi.org/10.1056/NEJMoa1304369] [PMID: 24131140]
[PMID: 12941842]
[http://dx.doi.org/10.3892/or.2014.3344] [PMID: 25051142]
[http://dx.doi.org/10.1016/j.biomaterials.2013.07.075] [PMID: 23932498]
[http://dx.doi.org/10.2147/IJN.S17336]
[http://dx.doi.org/10.1016/j.nano.2013.07.018] [PMID: 23969104]
[http://dx.doi.org/10.4172/2157-7439.1000164] [PMID: 24163786]
[http://dx.doi.org/10.1016/j.ajps.2018.10.003] [PMID: 32104482]
[http://dx.doi.org/10.1007/s13346-016-0342-7] [PMID: 27812915]
[http://dx.doi.org/10.1007/s13346-016-0318-7] [PMID: 27465619]
[http://dx.doi.org/10.1208/s12249-012-9865-5] [PMID: 23070560]
[http://dx.doi.org/10.1016/j.colsurfb.2012.05.019] [PMID: 22766282]
[http://dx.doi.org/10.1038/aps.2010.55] [PMID: 20523347]
[http://dx.doi.org/10.1517/13543776.2016.1111872] [PMID: 26651178]
[http://dx.doi.org/10.2147/IJN.S164518] [PMID: 29922053]
[http://dx.doi.org/10.1021/mp4006968] [PMID: 24621456]
[http://dx.doi.org/10.1002/mabi.201500317] [PMID: 26647779]
[http://dx.doi.org/10.1016/j.ijpharm.2018.03.017] [PMID: 29535039]
[http://dx.doi.org/10.1016/j.ijpharm.2013.05.034] [PMID: 23707964]
[http://dx.doi.org/10.1016/j.biomaterials.2011.09.017] [PMID: 21937102]
[http://dx.doi.org/10.1016/j.biopha.2018.11.110]
[http://dx.doi.org/10.1016/S0959-8049(98)00228-7] [PMID: 9893622]
[http://dx.doi.org/10.1159/000219422] [PMID: 13825526]
[http://dx.doi.org/10.3201/eid0904.020268] [PMID: 12702222]
[http://dx.doi.org/10.2165/00003088-200443070-00002] [PMID: 15139794]
[http://dx.doi.org/10.3390/antiox9010050] [PMID: 31935872]
[http://dx.doi.org/10.4274/tjps.galenos.2018.21043] [PMID: 32454706]
[http://dx.doi.org/10.1016/j.tiv.2017.03.007] [PMID: 28323104]
[http://dx.doi.org/10.5530/srp.2020.2.55]
[http://dx.doi.org/10.1039/C7TB01628J] [PMID: 32264380]
[http://dx.doi.org/10.1166/jbn.2013.1613] [PMID: 23909136]
[http://dx.doi.org/10.1517/13543776.2011.561784] [PMID: 21413912]
[http://dx.doi.org/10.4155/tde.11.128] [PMID: 22833986]
[http://dx.doi.org/10.1016/S0006-2952(97)00682-5] [PMID: 9605432]
[http://dx.doi.org/10.1371/journal.pone.0159052] [PMID: 27391697]
[http://dx.doi.org/10.1016/0378-5173(85)90143-7]
[http://dx.doi.org/10.1007/s11095-017-2283-3] [PMID: 29488022]
[http://dx.doi.org/10.1016/j.jsps.2014.11.010] [PMID: 26106279]
[http://dx.doi.org/10.1016/j.msec.2019.109828] [PMID: 31349496]
[http://dx.doi.org/10.1016/j.carbpol.2016.09.096] [PMID: 27987854]
[http://dx.doi.org/10.1016/j.apsusc.2017.08.228]
[http://dx.doi.org/10.1016/j.electacta.2015.08.036]
[http://dx.doi.org/10.1016/j.molliq.2014.10.013]
[http://dx.doi.org/10.1002/cmdc.201100321]
[http://dx.doi.org/10.1111/j.2042-7158.2012.01567.x] [PMID: 23278683]
[http://dx.doi.org/10.21608/ejh.2020.31011.1299]
[http://dx.doi.org/10.1159/000265166] [PMID: 20016174]
[http://dx.doi.org/10.1016/j.ijpharm.2020.120029] [PMID: 33130218]
[http://dx.doi.org/10.1080/21691401.2019.1581791] [PMID: 30888204]
[http://dx.doi.org/10.1007/s11655-014-2024-y] [PMID: 25428336]
[http://dx.doi.org/10.1016/j.matpr.2020.02.659]
[http://dx.doi.org/10.1111/bcp.12787] [PMID: 26382728]
[http://dx.doi.org/10.2174/1573412915666190314124932]
[http://dx.doi.org/10.1007/s13346-020-00803-7] [PMID: 32519202]
[http://dx.doi.org/10.1016/j.molliq.2020.113878]
[http://dx.doi.org/10.1111/jphp.12550] [PMID: 27018771]
[http://dx.doi.org/10.1016/j.colsurfb.2017.02.012] [PMID: 28231500]
[PMID: 23874006]
[http://dx.doi.org/10.1007/s12034-014-0030-5]
[http://dx.doi.org/10.1039/C5RA03546E]
[http://dx.doi.org/10.3390/pharmaceutics11020065] [PMID: 30717376]
[http://dx.doi.org/10.1039/C7NJ04864E]
[http://dx.doi.org/10.1177/0885328217698063] [PMID: 28447548]
[http://dx.doi.org/10.2147/IJN.S168400] [PMID: 30154652]
[http://dx.doi.org/10.1016/j.nano.2019.01.006] [PMID: 30708054]
[http://dx.doi.org/10.1021/acsomega.8b03212] [PMID: 30842986]
[http://dx.doi.org/10.2147/IJN.S211014] [PMID: 31308665]
[http://dx.doi.org/10.1016/j.saa.2020.118905] [PMID: 32927299]
[http://dx.doi.org/10.3390/pharmaceutics12040365] [PMID: 32316199]
[http://dx.doi.org/10.1021/acs.molpharmaceut.8b00206]
[http://dx.doi.org/10.1016/j.addr.2018.11.006] [PMID: 30529138]
[http://dx.doi.org/10.1166/jnn.2015.9248] [PMID: 26353739]
[http://dx.doi.org/10.3109/02652048.2015.1057252] [PMID: 26079598]
[http://dx.doi.org/10.1208/s12248-012-9433-7] [PMID: 23180162]
[http://dx.doi.org/10.22159/ajpcr.2021.v14i8.41987]
[http://dx.doi.org/10.1016/j.addr.2007.09.007] [PMID: 18155316]
[http://dx.doi.org/10.1016/j.ijpharm.2004.03.034] [PMID: 15488684]
[http://dx.doi.org/10.1208/s12249-019-1319-x] [PMID: 30790136]
[http://dx.doi.org/10.1016/j.xphs.2020.07.027] [PMID: 32745564]
[http://dx.doi.org/10.18433/jpps30097] [PMID: 30365396]
[http://dx.doi.org/10.3109/02652048.2012.726280] [PMID: 23101936]
[http://dx.doi.org/10.4314/tjpr.v14i4.2]
[http://dx.doi.org/10.3109/03639045.2012.718785] [PMID: 22998295]
[http://dx.doi.org/10.1002/jps.23858] [PMID: 24464737]
[http://dx.doi.org/10.1016/j.nano.2013.12.010] [PMID: 24407148]
[http://dx.doi.org/10.1080/03639045.2016.1239732] [PMID: 27648633]
[http://dx.doi.org/10.3390/molecules25071703] [PMID: 32276393]
[http://dx.doi.org/10.2147/IJN.S25824]
[http://dx.doi.org/10.3109/10717544.2013.878003] [PMID: 24512268]
[http://dx.doi.org/10.1016/j.ijbiomac.2020.02.275] [PMID: 32112841]
[http://dx.doi.org/10.2147/IJN.S121114] [PMID: 27942212]
[http://dx.doi.org/10.1016/j.colsurfb.2017.09.008] [PMID: 28917151]
[http://dx.doi.org/10.1016/j.xphs.2020.01.010] [PMID: 31954111]