Advancements in the oral delivery of Docetaxel: challenges, current state-of-the-art and future trends

Figures & data

Figure 1 (A) Chemical structure of Docetaxel and (B) graphical representation of the mechanism of action of Docetaxel.

Figure 2 Nanotechnology based emerging trends reported for the oral delivery of anticancer agents.

Abbreviation: SEDDS, self-emulsifying drug delivery systems.

Figure 3 Different cellular mechanisms involved in the cellular uptake and permeation of various nanoformulations across the enterocytes after oral administration.

Table 1 Different nano-based approaches used for the oral delivery of Docetaxel

Serial no.	Material	Characterization	Outcomes	References
Polymeric nanoparticles
1.	Polycaprolactone/Pluronic F-68	In vitro	Increased cytotoxicity and controlled drug release as compared to IV Docetaxel and Tween 80	^Citation81
2.	PLGA, vitamin E, montmorillonite	In vitro and in vivo	Improved oral pharmacokinetics with a 21-fold increased oral bioavailability and sustained release over 3 weeks as compared to IV Docetaxel and Tween 80. Also, a 3- to 4-fold increased anticancer activity was observed	^Citation82
3.	Polymethyl methacrylate, thiolated chitosan	In vivo	A 9-fold increased half-life and 96% increased oral bioavailability via increased permeation	^Citation83
4.	Lecithin	In vitro	The oral bioavailability was increased 3.65-fold as compared to a Docetaxel suspension	^Citation84
5.	Methyl-β-cyclodextrin and thiolated chitosan	In vivo	Improved oral bioavailability with a sustained release effect	^Citation85
6.	Sulfobutylether-β-cyclodextrin and chitosan	In vivo	A 1,447% increased oral bioavailability and decreased plasma clearance	^Citation134
7.	Methyl-β-cyclodextrin, polyisobutyl cyanoacrylate, thiolated chitosan	In vitro	Decreased enterocyte toxicity and inflammation as compared to IV Docetaxel and Tween 80	^Citation87
8.	Chitosan, PLGA		A 5-fold increased permeation and 5.11-fold increased anticancer activity against A549	^Citation88
9.	Glyceryl tributyrate, oleoyl polyoxylglycerides and PLGA 4000 NC embeded in Eudragit L and HPMC microparticles	In vivo and in vitro	A 10- and 8.4-fold improved oral bioavailability and Cmax compared with IV Docetaxel and Tween 80. Increased antitumor effect against metastatic lung cancer	^Citation102
Lipid-based nanocarriers
10.	Oleic acid–Docetaxel prodrug	In vivo and in vitro	A 4.04-fold increased oral bioavailability as compared to Docetaxel	^Citation95
11.	Cysteine-modified lipid nanocarriers with PEG 2000	In vivo and in vitro	A 13-fold increased AUC as compared to Docetaxel	^Citation96
12.	DTGPS 1000, Tween 80	In vivo and in vitro	Increased oral bioavailability as compared to IV Docetaxel and Tween 80 via P-gp blocking and lymphatic uptake	^Citation97
Hybrid nanocarriers
13.	Polymeric core–lipid shell	In vitro	Sustained release and 94% better cytotoxicity as compared to IV Docetaxel and Tween 80	^Citation99
14.	Mixed lipid core and folate grafter thiolated chitosan shell	In vivo and in vitro	A 9.6-fold increased permeation and 13.6-fold increased oral bioavailability as compared to Docetaxel suspension	^Citation100
15.	Carboxymethyl chitosan, phospholipids, mesoporous carbon NPs	In vitro	Improved mucoadhesion, sustained drug release in gastric pH and improved anticancer activity	^Citation101
Theranostic nanocarriers
16.	Liposomes, TPGS with quantum dots	In vitro	Improved cellular uptake with a 41-fold increased cytotoxicity as compared to IV Docetaxel and Tween 80	^Citation103
17.	SPION, PLGA, folate-chitosan	In vitro	Improved cellular uptake and shortened T2 relaxation time for better imaging	^Citation104
Emulsions
18.	Microemulsion Caproyl 90, Cremophor EL, Transcutol	In vivo and in vitro	A 34.3% increased oral bioavailability as compared to IV Docetaxel and Tween 80. Sustained release over 12 hours	^Citation105
19.	Nanoemulsion soybean oil, lecithin, Pluronic F68, PEG 4000	In vitro	2.8-fold increase in cellular uptake and least toxic effect against a MCF-7 cell line	^Citation106
20.	Frankincense oil-based nanoemulsion	In vivo and in vitro	182.5-fold increased relative oral bioavailability and 19% increased anticancer activity against MDA-MB-231	^Citation107
Self-emulsifying drug delivery systems
21.	SNEDDS Capryol 90, labrasol, Transcutol HP	In vivo	17% increased oral bioavailability and antitumor activity as compared to IV Docetaxel and Tween 80	^Citation108
22.	SNEDDS based on colloidal silica	In vivo	12.5% increased oral bioavailability as compared to a Docetaxel solution	^Citation109
23.	Supersaturable self-emulsifying drug delivery system	In vivo and in vitro	Improved oral bioavailability by 8.77-fold and AUC by 1.45-fold as compared to IV Docetaxel and Tween 80	^Citation110
24.	SEDDS curcumin	In vivo	2.6- to 4.4-fold increased Cmax and 2.4- to 3.2-fold improved oral bioavailability	^Citation111
25.	SEDDS Caproyl 90, vitamin E, Gelucire 44/14 and Transcutol HP	In vitro and in vivo	A 3.19-fold increased oral bioavailability and a 25-fold increased cytotoxicity	^Citation112
Polymer–drug conjugates
26.	Chitosan–Docetaxel	In vivo and in vitro	15-fold increased half-life as compared to a Docetaxel solution and decreased toxicity	^Citation113
27.	Taurocholic acid–heparin–Docetaxel	In vivo and in vitro	6-fold increased oral bioavailability with improved tumor targeting and uptake in MDA-MB-231 cells	^Citation114
28.	Carboxymethyl chitosan–Docetaxel	In vivo and in vitro	Improved oral bioavailability and tumor targeting with a 4-fold decreased toxicity	^Citation115
Polymeric micelles
29.	Polycaprolactone, PEG	In vivo and in vitro	10-fold increased oral bioavailability in a pH-sensitive hydrogel and effective at inhibiting tumor growth in a 4T1 breast cancer model	^Citation118
30.	β-casein	In vivo and in vitro	Improved oral bioavailability and toxicity	^Citation119
31.	Co-block polymeric micelles	In vivo and in vitro	2.52-fold increase in oral bioavailability with sustained drug release	^Citation120
32.	Steric acid-modified Bletilla striata	In vivo	2- to 4-fold increased oral bioavailability as compared to IV Docetaxel	^Citation121
33.	Co-block mixed polymer biotin-modified micelles in alginate microparticles	In vivo and in vitro	27.4-fold increased oral bioavailability and an 84% increased cytotoxicity as compared to Docetaxel	^Citation122
34.	Tween 20 and Tween 80	In vitro	Improved solubility up to 1500-fold with higher anticancer activity against a C26 colon cancer cell line	^Citation123
35.	Methoxy poly(ethylene glycol)-poly(lactide)	In vitro and in vivo	84.4% inhibition of an oral epidermoid tumor	^Citation124
Proniosome
36.	TPGS proniosomes	In vitro and in vivo	7.3-fold increased oral bioavailability and increased anticancer activity in MCF-7 tumor-bearing mice model	^Citation127
Solid dispersion
37.	Poloxamer F68/P85	In vitro and in vivo	2.97-fold increased oral bioavailability	^Citation124

Abbreviations: AUC, area under the curve; IV, intravenous; NP, nanoparticle; PEG, polyethylene glycol; PLGA, poly(lactic-co-glycolic acid); SNEDDS, self-nanoemulsifying drug delivery systems; SPION, superparamagnetic iron oxide nanoparticles; TPGS, docetaxel-loaded d-α-tocopheryl polyethylene glycol 1000 succinate.

MeiLZhangYZhengYA novel docetaxel-loaded poly (ε-caprolactone)/pluronic F68 nanoparticle overcoming multidrug resistance for breast cancer treatmentNanoscale Res Lett2009412153020652101

 PubMed Web of Science ®Google Scholar

FengS-SMeiLAnithaPGanCWZhouWPoly (lactide)–vitamin E derivative/montmorillonite nanoparticle formulations for the oral delivery of DocetaxelBiomaterials200930193297330619299012

 PubMed Web of Science ®Google Scholar

SaremiSDinarvandRKebriaeezadehAOstadSNAtyabiFEnhanced oral delivery of docetaxel using thiolated chitosan nanoparticles: preparation, in vitro and in vivo studiesBiomed Res Int20132013

 PubMed Web of Science ®Google Scholar

HuKCaoSHuFFengJEnhanced oral bioavailability of docetaxel by lecithin nanoparticles: preparation, in vitro, and in vivo evaluationInt J Nanomedicine201273537354522848177

 PubMed Web of Science ®Google Scholar

MazzaferroSBouchemalKSkanjiRGueutinCChacunHPonchelGIntestinal permeation enhancement of docetaxel encapsulated into methyl-β-cyclodextrin/poly (isobutylcyanoacrylate) nanoparticles coated with thiolated chitosanJ Control Release2012162356857422902592

 PubMed Web of Science ®Google Scholar

WuJShenQFangLSulfobutylether-β-cyclodextrin/chitosan nanoparticles enhance the oral permeability and bioavailability of docetaxelDrug Dev Ind Pharm20133971010101922681515

 PubMed Web of Science ®Google Scholar

WuJBuXDouLFangLShenQCo-delivery of Docetaxel and Berbamine by Chitosan/Sulfobutylether-β-Cyclodextrin nanoparticles for enhancing bioavailability and anticancer activitiesJ Biomed Nanotechnol201511101847185726502647

 PubMed Web of Science ®Google Scholar

AhmadNAlamMAAhmadRNaqviAAAhmadFJPreparation and characterization of surface-modified PLGA-polymeric nanoparticles used to target treatment of intestinal cancerArtif Cells Nanomed Biotechnol201846243244628503995

 PubMed Web of Science ®Google Scholar

Attili-QadriSKarraNNemirovskiAOral delivery system prolongs blood circulation of docetaxel nanocapsules via lymphatic absorptionProc Natl Acad Sci U S A201311043174981750324101508

 PubMed Web of Science ®Google Scholar

SunBLuoCLiLCore-matched encapsulation of an oleate prodrug into nanostructured lipid carriers with high drug loading capability to facilitate the oral delivery of docetaxelColloids Surf B Biointerfaces2016143475527011346

 PubMed Web of Science ®Google Scholar

FangGTangBChaoYCysteine-functionalized nanostructured lipid carriers for oral delivery of docetaxel: a permeability and pharmacokinetic studyMol Pharm20151272384239525974386

 PubMedGoogle Scholar

ChoH-JParkJWYoonI-SKimD-DSurface-modified solid lipid nanoparticles for oral delivery of docetaxel: enhanced intestinal absorption and lymphatic uptakeInt J Nanomedicine2014949524531717

 PubMed Web of Science ®Google Scholar

LiuYLiKPanJLiuBFengS-SFolic acid conjugated nanoparticles of mixed lipid monolayer shell and biodegradable polymer core for targeted delivery of DocetaxelBiomaterials201031233033819783040

 PubMed Web of Science ®Google Scholar

SohailMFJavedIHussainSZFolate grafted thiolated chitosan enveloped nanoliposomes with enhanced oral bioavailability and anticancer activity of docetaxelJ Mater Chem B201643762406248

 PubMed Web of Science ®Google Scholar

ZhangYZhuWZhangHCarboxymethyl chitosan/phospholipid bilayer-capped mesoporous carbon nanoparticles with pH-responsive and prolonged release properties for oral delivery of the antitumor drug, DocetaxelInt J Pharm2017532138439228903067

 PubMedGoogle Scholar

MuthuMSKulkarniSARajuAFengS-STheranostic liposomes of TPGS coating for targeted co-delivery of docetaxel and quantum dotsBiomaterials201233123494350122306020

 PubMed Web of Science ®Google Scholar

ShanavasASasidharanSBahadurDSrivastavaRMagnetic core-shell hybrid nanoparticles for receptor targeted anti-cancer therapy and magnetic resonance imagingJ Colloid Interface Sci201748611212027697648

 PubMed Web of Science ®Google Scholar

YinY-MCuiF-DMuC-FDocetaxel microemulsion for enhanced oral bioavailability: preparation and in vitro and in vivo evaluationJ Control Release20091402869419709639

 PubMed Web of Science ®Google Scholar

VermaPMeherJGAsthanaSPawarVKChaurasiaMChourasiaMKPerspectives of nanoemulsion assisted oral delivery of docetaxel for improved chemotherapy of cancerDrug Deliv201623247948824901205

 PubMed Web of Science ®Google Scholar

PandeyGMittapellyNValicherlaGRP-gp modulatory acetyl-11-keto-β-boswellic acid based nanoemulsified carrier system for augmented oral chemotherapy of docetaxelColloids Surf B Biointerfaces201715527628628437753

 PubMed Web of Science ®Google Scholar

SeoYGKimDHRamasamyTDevelopment of docetaxel-loaded solid self-nanoemulsifying drug delivery system (SNEDDS) for enhanced chemotherapeutic effectInt J Pharm2013452141242023707964

 PubMedGoogle Scholar

QuanQKimD-WMarasiniNPhysicochemical characterization and in vivo evaluation of solid self-nanoemulsifying drug delivery system for oral administration of docetaxelJ Microencapsul201330430731423101936

 PubMed Web of Science ®Google Scholar

ChenYChenCZhengJChenZShiQLiuHDevelopment of a solid supersaturatable self-emulsifying drug delivery system of docetaxel with improved dissolution and bioavailabilityBiol Pharm Bull201134227828621415541

 PubMed Web of Science ®Google Scholar

YanY-DMarasiniNChoiYKEffect of dose and dosage interval on the oral bioavailability of docetaxel in combination with a curcumin self-emulsifying drug delivery system (SEDDS)Eur J Drug Metab Pharmacokinet201237321722422201019

 PubMed Web of Science ®Google Scholar

ValicherlaGRDaveKMSyedAAFormulation optimization of Docetaxel loaded self-emulsifying drug delivery system to enhance bioavailability and anti-tumor activitySci Rep201662689527241877

 PubMed Web of Science ®Google Scholar

LeeEKimHLeeI-HJonSIn vivo antitumor effects of chitosan-conjugated docetaxel after oral administrationJ Control Release20091402798519712714

 PubMed Web of Science ®Google Scholar

KhatunZNurunnabiMReeckGRChoKJLeeY-KOral delivery of taurocholic acid linked heparin–docetaxel conjugates for cancer therapyJ Control Release20131701748223665255

 PubMed Web of Science ®Google Scholar

LiuFFengLZhangLZhangXZhangNSynthesis, characterization and antitumor evaluation of CMCS–DTX conjugates as novel delivery platform for docetaxelInt J Pharm20134511414923608199

 PubMedGoogle Scholar

WangYChenLTanLPEG–PCL based micelle hydrogels as oral docetaxel delivery systems for breast cancer therapyBiomaterials201435256972698524836952

 PubMed Web of Science ®Google Scholar

ShapiraAAssarafYGEpsteinDLivneyYDBeta-casein nanoparticles as an oral delivery system for chemotherapeutic drugs: impact of drug structure and properties on co-assemblyPharm Res201027102175218620703895

 PubMed Web of Science ®Google Scholar

DouJZhangHLiuXZhangMZhaiGPreparation and evaluation in vitro and in vivo of docetaxel loaded mixed micelles for oral administrationColloids Surf B Biointerfaces2014114202724157590

 PubMed Web of Science ®Google Scholar

GuanQSunDZhangGDocetaxel-loaded self-assembly stearic acid-modified bletilla striata polysaccharide micelles and their anticancer effect: preparation, characterization, cellular uptake and in vitro evaluationMolecules201621121641

 PubMed Web of Science ®Google Scholar

ShenYHuMQiuLSequentially dual-targeting vector with nano-in-micro structure for improved docetaxel oral delivery in vivoNanomedicine201611233071308627728994

 PubMed Web of Science ®Google Scholar

HekmatAAttarHSeyf KordiAAImanMJaafariMRNew oral formulation and in vitro evaluation of Docetaxel-loaded nanomicellesMolecules20162191265

 PubMed Web of Science ®Google Scholar

SongCKYoonI-SKimD-DPoloxamer-based solid dispersions for oral delivery of docetaxel: Differential effects of F68 and P85 on oral docetaxel bioavailabilityInt J Pharm2016507110210827154250

 PubMedGoogle Scholar

LiuHTuLZhouYImproved bioavailability and antitumor effect of Docetaxel by TPGS modified proniosomes: in vitro and in vivo evaluationsSci Rep2017711128127051

 PubMed Web of Science ®Google Scholar