Abstract
Background: Cancer is the major public health problem in developing countries. The treatment of cancer requires a multimodal approach and chemotherapy is one of them. Chemotherapeutic drug is administered to cancer patients in the form of a formulation which is prepared by mixing an active ingredient (drug) with the excipient. The role of excipient in a formulation is to regulate the release, bio-distribution, and selectivity of drug within the body.
Methods: In this context, selectivity of an anticancer formulation is achieved through two mechanisms like passive and active targeting. The passive targeting of a formulation is generally through enhanced permeation retention (EPR) effect which is dictated by physical properties of the carrier such as shape and size. On the contrary, active targeting means surface functionalization of excipient with target-specific ligands and/or receptors to increase its selectivity.
Results: Over the past several decades, remarkable progress has been made in the development and application of an engineered excipient or carrier to treat cancer more effectively. Especially nanoparticulate systems composed of metal/liposomes/polymeric material/proteins have received significant attention in the rational design of anticancer drug formulations; for example, therapeutic agents have been integrated with nanoparticles of optimal sizes, shapes and surface properties to improve their solubility, circulation half-life, and bio-distribution. In this review article, recent literature is included to discuss the role of physicochemical properties of excipients in achieving tumour targeting through passive and active approaches.
Conclusion: The selection of an excipient/carrier and targeting ligand plays a very important role in rational design and development of anticancer drug formulations.
Keywords: Anticancer formulation, nano delivery system, passive targeting, active targeting, clinical application, nanoparticulate systems.
[http://dx.doi.org/10.1186/1476-069X-10-S1-S2]
[http://dx.doi.org/10.1016/j.addr.2015.10.022] [PMID: 26546751]
[http://dx.doi.org/10.1039/C5NR07161E] [PMID: 26731460]
[PMID: 29234213]
[http://dx.doi.org/10.3390/molecules23040826] [PMID: 29617302]
[http://dx.doi.org/10.1186/s12951-018-0392-8] [PMID: 30231877]
[http://dx.doi.org/10.1016/j.tips.2009.08.004] [PMID: 19837467]
[http://dx.doi.org/10.1016/j.jconrel.2014.04.047] [PMID: 24816069]
[http://dx.doi.org/10.2147/IJN.S35576] [PMID: 23028220]
[http://dx.doi.org/10.3389/fphar.2015.00286] [PMID: 26648870]
[http://dx.doi.org/10.4103/0250-474X.57282] [PMID: 20502539]
[http://dx.doi.org/10.15171/apb.2015.043] [PMID: 26504751]
[http://dx.doi.org/10.1016/j.jconrel.2015.10.006] [PMID: 26450667]
[http://dx.doi.org/10.1007/978-1-60761-609-2_11] [PMID: 20217595]
[http://dx.doi.org/10.1016/j.ijpharm.2017.06.052] [PMID: 28629982]
[http://dx.doi.org/10.3109/02652048.2011.569763] [PMID: 21545323]
[http://dx.doi.org/10.3390/ma10050517] [PMID: 28772877]
[http://dx.doi.org/10.1016/S1773-2247(10)50056-X]
[http://dx.doi.org/10.1371/journal.pone.0191741] [PMID: 29364955]
[http://dx.doi.org/10.1371/journal.pone.0193339] [PMID: 29513721]
[http://dx.doi.org/10.1016/j.bbagen.2006.06.012] [PMID: 16904830]
[http://dx.doi.org/10.1016/j.bbagen.2007.11.016] [PMID: 18178166]
[http://dx.doi.org/10.1080/10717544.2018.1489430] [PMID: 30044159]
[http://dx.doi.org/10.4103/0250-474X.180250] [PMID: 27168683]
[http://dx.doi.org/10.1146/annurev-virology-100114-055141] [PMID: 26958921]
[http://dx.doi.org/10.1007/978-1-4939-7808-3_28] [PMID: 29869258]
[http://dx.doi.org/10.1517/17425247.2010.498473] [PMID: 20645671]
[http://dx.doi.org/10.1016/j.cej.2019.03.272]
[http://dx.doi.org/10.1016/j.jconrel.2019.02.015] [PMID: 30771414]
[http://dx.doi.org/10.1016/j.clay.2015.04.018]
[http://dx.doi.org/10.1039/C6TB03146C]
[http://dx.doi.org/10.4103/0975-7406.72127] [PMID: 21180459]
[http://dx.doi.org/10.1016/j.jsps.2014.11.013] [PMID: 27330378]
[http://dx.doi.org/10.1021/acsami.8b21820] [PMID: 30773883]
[http://dx.doi.org/10.1021/acsbiomaterials.7b00569]
[http://dx.doi.org/10.1111/jcmm.12164] [PMID: 24237862]
[http://dx.doi.org/10.2147/vhrm.2006.2.3.213] [PMID: 17326328]
[http://dx.doi.org/10.3389/fonc.2018.00248] [PMID: 30013950]
[PMID: 2946403]
[http://dx.doi.org/10.1186/2040-2384-2-14] [PMID: 20701757]
[http://dx.doi.org/10.1155/2014/801896] [PMID: 24719887]
[http://dx.doi.org/10.1016/j.nantod.2015.06.006] [PMID: 26640510]
[http://dx.doi.org/10.1073/pnas.1411499111] [PMID: 25316794]
[http://dx.doi.org/10.2217/nnm.16.5] [PMID: 27003448]
[http://dx.doi.org/10.1021/acs.bioconjchem.7b00252] [PMID: 28574255]
[http://dx.doi.org/10.1038/s41598-018-19628-z] [PMID: 29391477]
[http://dx.doi.org/10.1039/C8CC00977E] [PMID: 29662978]
[http://dx.doi.org/10.1021/acsnano.5b03184] [PMID: 26256227]
[http://dx.doi.org/10.1016/j.colsurfa.2019.01.043]
[http://dx.doi.org/10.1016/j.colsurfb.2017.07.048] [PMID: 28783613]
[http://dx.doi.org/10.1002/cbin.10459] [PMID: 25790433]
[http://dx.doi.org/10.1021/nl403949h] [PMID: 24383757]
[http://dx.doi.org/10.1002/adhm.201400641] [PMID: 25641794]
[http://dx.doi.org/10.1021/la062642r] [PMID: 17279633]
[http://dx.doi.org/10.2217/nnm.13.191] [PMID: 24354814]
[http://dx.doi.org/10.2147/IJN.S36111] [PMID: 23144561]
[http://dx.doi.org/10.1186/s11671-018-2728-6] [PMID: 30361809]
[http://dx.doi.org/10.1021/ic301050v] [PMID: 22873404]
[http://dx.doi.org/10.1039/C8SC01828F] [PMID: 29997881]
[http://dx.doi.org/10.1016/j.bpj.2009.07.009] [PMID: 19751661]
[http://dx.doi.org/10.1016/j.biomaterials.2011.01.021] [PMID: 21295849]
[http://dx.doi.org/10.1016/j.nantod.2015.06.006] [PMID: 26640510]
[http://dx.doi.org/10.1021/acsnano.5b03184] [PMID: 26256227]
[http://dx.doi.org/10.1038/nnano.2011.58] [PMID: 21516092]
[http://dx.doi.org/10.3762/bjnano.5.174] [PMID: 25383275]
[http://dx.doi.org/10.1021/nl072053l] [PMID: 17983249]
[http://dx.doi.org/10.1016/j.bmc.2017.06.040] [PMID: 28705434]
[http://dx.doi.org/10.1081/LPR-120020318] [PMID: 12855110]
[http://dx.doi.org/10.1371/journal.pone.0050028] [PMID: 23185522]
[http://dx.doi.org/10.1038/s41467-017-02588-9] [PMID: 29317633]
[http://dx.doi.org/10.2147/IJN.S165210] [PMID: 30013345]
[http://dx.doi.org/10.1038/nrc1456] [PMID: 15510161]
[http://dx.doi.org/10.4137/DTI.S12519] [PMID: 24023511]
[http://dx.doi.org/10.1016/j.biomaterials.2017.06.037] [PMID: 28688285]
[http://dx.doi.org/10.2147/IJN.S165210] [PMID: 30013345]
[PMID: 22896759]
[http://dx.doi.org/10.1038/nrc3930] [PMID: 25998715]
[http://dx.doi.org/10.1002/jsscb.1981.380160305] [PMID: 7031274]
[http://dx.doi.org/10.1016/j.ijpharm.2014.10.045] [PMID: 25445515]
[http://dx.doi.org/10.1080/19420862.2018.1518887] [PMID: 30252602]
[http://dx.doi.org/10.1038/374143a0] [PMID: 7877686]
[http://dx.doi.org/10.1080/19420862.2016.1168960] [PMID: 27031922]
[http://dx.doi.org/10.1517/17425240903579963] [PMID: 20331354]
[http://dx.doi.org/10.1016/j.jconrel.2012.05.052] [PMID: 22709588]
[PMID: 12234975]
[http://dx.doi.org/10.1080/10717544.2019.1587047] [PMID: 30905205]
[PMID: 27385913]
[http://dx.doi.org/10.3389/fonc.2013.00216] [PMID: 23986882]
[http://dx.doi.org/10.1021/jp711477k] [PMID: 18588341]
[http://dx.doi.org/10.1038/s41388-018-0213-4] [PMID: 29662195]
[http://dx.doi.org/10.1039/C7SC04004K] [PMID: 29675145]
[http://dx.doi.org/10.1021/acs.chemrev.7b00042] [PMID: 28654243]
[http://dx.doi.org/10.1248/bpb.34.1338] [PMID: 21804229]
[http://dx.doi.org/10.3390/ijms17050676] [PMID: 27196894]
[PMID: 29666835]
[http://dx.doi.org/10.1016/j.addr.2013.11.009] [PMID: 24270007]
[http://dx.doi.org/10.1016/j.addr.2008.03.016] [PMID: 18555555]
[http://dx.doi.org/10.1186/s40824-018-0123-0] [PMID: 29686885]
[http://dx.doi.org/10.7150/thno.14856] [PMID: 27217831]
[http://dx.doi.org/10.4049/jimmunol.178.11.7181] [PMID: 17513767]
[http://dx.doi.org/10.1039/C7CS00011A] [PMID: 28191579]
[http://dx.doi.org/10.1111/j.1476-5381.2009.00604.x] [PMID: 20132208]
[http://dx.doi.org/10.1021/ci200319e] [PMID: 22087588]
[http://dx.doi.org/10.1039/C7CP08644J] [PMID: 29445792]
[http://dx.doi.org/10.1016/j.nano.2012.05.015] [PMID: 22687896]
[http://dx.doi.org/10.1021/acsami.8b18843] [PMID: 30521749]
[http://dx.doi.org/10.1073/pnas.0404039101] [PMID: 15528279]
[http://dx.doi.org/10.1021/acs.jpcb.6b08667] [PMID: 27723331]
[http://dx.doi.org/10.1021/acsnano.5b00415] [PMID: 25853367]
[http://dx.doi.org/10.1016/j.molonc.2009.05.009] [PMID: 19596615]
[http://dx.doi.org/10.1002/wnan.1389] [PMID: 26762467]
[http://dx.doi.org/10.1186/1556-276X-9-520] [PMID: 25288914]
[http://dx.doi.org/10.1039/C5CS00798D] [PMID: 26776487]
[http://dx.doi.org/10.1038/srep10560] [PMID: 25976444]
[http://dx.doi.org/10.1016/j.mattod.2015.11.025]
[http://dx.doi.org/10.17219/acem/30428] [PMID: 27627574]
[http://dx.doi.org/10.1021/mp500710x] [PMID: 25751168]
[http://dx.doi.org/10.1002/med.21485] [PMID: 29341223]
[http://dx.doi.org/10.1371/journal.pone.0115636] [PMID: 25695795]
[http://dx.doi.org/10.1142/S1793984410000067] [PMID: 24348868]
[http://dx.doi.org/10.3389/fchem.2014.00086] [PMID: 25353018]
[http://dx.doi.org/10.1039/c3tb20901f]
[http://dx.doi.org/10.1039/C6PY01082B]
[http://dx.doi.org/10.1166/jnn.2012.6180] [PMID: 22905487]
[http://dx.doi.org/10.18632/oncotarget.17976] [PMID: 28978003]
[http://dx.doi.org/10.1007/978-1-4939-6646-2_3] [PMID: 28150195]
[http://dx.doi.org/10.3390/molecules23040826] [PMID: 29617302]
[http://dx.doi.org/10.3109/10717544.2014.882469] [PMID: 24524308]
[PMID: 25258529]
[http://dx.doi.org/10.1016/j.carbpol.2018.06.055] [PMID: 30093044]
[http://dx.doi.org/10.1097/CAD.0000000000000586] [PMID: 29381491]
[http://dx.doi.org/10.1021/acsami.7b18493] [PMID: 29457719]
[http://dx.doi.org/10.1021/acsami.5b03866] [PMID: 26168166]
[http://dx.doi.org/10.1007/s11095-013-1151-z] [PMID: 23921489]
[http://dx.doi.org/10.1016/j.biomaterials.2013.06.066] [PMID: 23876758]
[http://dx.doi.org/10.1155/2018/8467169]
[http://dx.doi.org/10.1021/jf4001567] [PMID: 23414105]
[http://dx.doi.org/10.1016/j.ijpharm.2018.02.042] [PMID: 29496457]
[http://dx.doi.org/10.1021/acsami.8b00875] [PMID: 29481741]
[http://dx.doi.org/10.1080/10717544.2018.1428245] [PMID: 29350051]
[http://dx.doi.org/10.2147/IJN.S108689] [PMID: 27574421]
[http://dx.doi.org/10.1016/j.ejps.2015.12.019] [PMID: 26699227]
[http://dx.doi.org/10.1002/adhm.201200296] [PMID: 23225538]
[http://dx.doi.org/10.3109/1061186X.2012.729214] [PMID: 23036042]
[http://dx.doi.org/10.1007/s13758-011-0005-7] [PMID: 22589048]
[http://dx.doi.org/10.1089/cbr.2009.0724] [PMID: 20735207]
[http://dx.doi.org/10.1155/2011/768201]
[http://dx.doi.org/10.1021/acsabm.8b00526]
[http://dx.doi.org/10.1016/j.msec.2017.08.007]
[http://dx.doi.org/10.1021/acsami.6b07583] [PMID: 27537061]
[http://dx.doi.org/10.1016/j.colsurfb.2012.09.010] [PMID: 23107962]
[http://dx.doi.org/10.1016/j.ejpb.2011.10.022] [PMID: 22085654]
[http://dx.doi.org/10.1016/0378-5173(94)90005-1]
[http://dx.doi.org/10.1007/s11095-010-0222-7] [PMID: 20703895]
[http://dx.doi.org/10.3390/molecules21030282] [PMID: 26999081]
[http://dx.doi.org/10.1016/j.colsurfb.2018.09.047] [PMID: 30261346]
[http://dx.doi.org/10.1023/A:1022656105022] [PMID: 12669962]
[http://dx.doi.org/10.1158/0008-5472.CAN-05-1093] [PMID: 16357174]
[PMID: 25092965]
[http://dx.doi.org/10.1016/j.ijpharm.2007.04.037] [PMID: 17583453]
[http://dx.doi.org/10.1016/j.ejpb.2017.02.020] [PMID: 28257810]
[http://dx.doi.org/10.1038/cgt.2015.18] [PMID: 25857361]
[http://dx.doi.org/10.1038/ncomms4546] [PMID: 24699423]
[http://dx.doi.org/10.1016/j.jconrel.2017.06.027] [PMID: 28666726]
[http://dx.doi.org/10.1021/acs.langmuir.6b00511] [PMID: 26987014]
[http://dx.doi.org/10.1016/j.jconrel.2015.12.006] [PMID: 26682502]
[http://dx.doi.org/10.3390/polym10010074] [PMID: 30966109]
[PMID: 30022700]
[PMID: 26677454]
[http://dx.doi.org/10.1039/c2ib20108a] [PMID: 22890797]
[http://dx.doi.org/10.1021/nn300524f] [PMID: 22409425]
[http://dx.doi.org/10.1016/j.biomaterials.2013.05.055] [PMID: 23777916]
[http://dx.doi.org/10.1007/s10856-017-5943-2] [PMID: 28819929]
[http://dx.doi.org/10.1039/C6RA05202A]
[http://dx.doi.org/10.1007/s11051-015-3118-y]
[http://dx.doi.org/10.4155/tde.14.115] [PMID: 25853307]
[http://dx.doi.org/10.2147/IJN.S92336] [PMID: 26648714]
[http://dx.doi.org/10.1016/j.biopha.2014.08.013] [PMID: 25194441]
[http://dx.doi.org/10.1080/10837450.2018.1507038] [PMID: 30063165]
[http://dx.doi.org/10.2147/IJN.S108768] [PMID: 27785020]
[http://dx.doi.org/10.1016/j.msec.2017.08.021] [PMID: 28888010]
[http://dx.doi.org/10.1039/C7BM00335H] [PMID: 28589972]
[http://dx.doi.org/10.1007/s10856-017-5902-y] [PMID: 28497362]
[http://dx.doi.org/10.1016/j.procbio.2015.10.007]
[http://dx.doi.org/10.1208/s12248-015-9828-3] [PMID: 26381779]
[http://dx.doi.org/10.1016/j.colsurfb.2015.07.022] [PMID: 26241913]
[http://dx.doi.org/10.1016/j.ijbiomac.2015.06.022] [PMID: 26093321]
[http://dx.doi.org/10.1166/sam.2016.2673]
[http://dx.doi.org/10.1016/j.xphs.2018.06.009] [PMID: 29935296]
[http://dx.doi.org/10.1016/j.ijpharm.2017.09.019] [PMID: 28893585]
[http://dx.doi.org/10.1002/jcp.25980] [PMID: 28464242]
[http://dx.doi.org/10.3762/bjnano.5.144] [PMID: 25247114]
[http://dx.doi.org/10.1016/j.msec.2009.01.021]
[http://dx.doi.org/10.2147/IJN.S128270] [PMID: 28435261]
[http://dx.doi.org/10.1208/s12249-013-9999-0] [PMID: 23934434]
[http://dx.doi.org/10.1038/s41467-018-05118-3] [PMID: 30006596]
[http://dx.doi.org/10.1016/j.ejpb.2013.01.028] [PMID: 23485475]
[http://dx.doi.org/10.3390/pharmaceutics5020246] [PMID: 24300449]
[http://dx.doi.org/10.1517/14656566.3.12.1739] [PMID: 12472371]
[PMID: 17717964]
[PMID: 11363534]
[http://dx.doi.org/10.1023/A:1008348010437] [PMID: 10690390]
[http://dx.doi.org/10.1200/JCO.2005.04.937] [PMID: 16172456]
[http://dx.doi.org/10.1517/13543780903114168] [PMID: 19604121]
[http://dx.doi.org/10.1007/s10637-006-8221-6] [PMID: 16699974]
[http://dx.doi.org/10.1021/ja5038269] [PMID: 24902769]
[http://dx.doi.org/10.1158/1535-7163.MCT-09-0763] [PMID: 20371718]
[http://dx.doi.org/10.1158/1078-0432.CCR-10-0978] [PMID: 20876255]
[http://dx.doi.org/10.1016/j.canlet.2004.02.004] [PMID: 15159019]
[http://dx.doi.org/10.1093/annonc/mdh092] [PMID: 14998859]
[http://dx.doi.org/10.3109/02656739709023559] [PMID: 9421741]
[http://dx.doi.org/10.1007/s10637-008-9208-2] [PMID: 19148580]