Review of Curcumin Physicochemical Targeting Delivery System

Figures & data

Figure 1 Pharmacological activities of Curcumin.

Abbreviations: PIV-3, parainfluenza virus type 3; FIPV, feline infectious peritonitis virus; VSV, vesicular stomatitis virus; HSV, herpes simplex virus; FHV, flock house virus; RSV, respiratory syncytial virus; HIV-1, type 1 human immunodeficiency virus; HSV-1, herpes simplex virus type 1; HBV hepatitis B virus; HCV hepatitis C virus; HPVs, high-risk human papillomaviruses; JEV, Japanese encephalitis virus; HTLV-1, human T-cell leukemia virus type 1.

Table 1 The Influential Effect and Preparation Method of CUR-Loaded Physicochemical Targeting Preparations

Preparations	Influential Effects	Preparation Method	Size	Ref.
pH-sensitive
Liposome	Enhanced inhibitory effect on EC109	Thin-film dispersion	141 nm	^Citation40
	Effectively transported to mouse (C57BL/6 mice bearing) tumor and significantly inhibited mouse tumor growth	Ultrasonic film hydration	193 nm	^Citation41
	Superior cytotoxic activity and proapoptotic against both HL-60 and HL-60/CDDP cells	Lipid film hydration method and extrusion	127 nm	^Citation42
	Anti-inflammatory and antioxidant activity in vitro	Micellar-vesicle transformation method and pH-driven method	<100 nm	^Citation43
Nanoparticle	1) Efficiently penetrate the blood–brain barrier and enhance brain delivery efficiency; 2) Increase mouse survival rate and reduce adverse reactions	Single-emulsion solvent evaporation method	100 nm	^Citation35
	Colonic specific drug release	Solvent emulsion evaporation technique	111 nm	^Citation44
	Enhanced permeation across Caco-2 cell and significantly decreased neutrophil infiltration and TNF-a secretion	Modified spontaneous emulsification solvent diffusion method	116 nm	^Citation46
	Double inhibition of the cancerous cells	Solvent emulsion-evaporation technique	97 nm	^Citation47
	Significantly released at pH 7.0	Ionic-gelation method	173 nm	^Citation48
	Enhanced significant cytotoxicity against MRC5 cells	Rotary evaporation and deposition coating	234 nm	^Citation50
	Delivered effectively drug to tumor and improved targeting ability	Co-condensation and coated method	about 80 nm	^Citation51
Micelle	Increased the tumor inhibition for HeLa, SiHa, and C33a cervical cell lines	Dialysis method	95 nm	^Citation57
	Extended the MRT and delayed the clearance of CUR	Solvent evaporation method	143 nm	^Citation58
	Inhibited tumor growth and exert MDR	Synthesis and self-assemble	228 nm	^Citation60
	Release rapidly CUR at the acidic environment	Synthesis and self-assemble	222 nm	^Citation61
Microsphere	1) Prevented premature release and controlled release; 2) Significantly reduced severity of colonic damage	Emulsion cross-linking method followed by coating	77 nm	^Citation66
Molecular complexes	1) Enhanced the aqueous solubility (>2 mg/mL); 2) Increased peak plasma concentration (6 times); 3) Improved bioavailability (about 20-fold)	Nanoprecipitation method	-	^Citation67
Microcapsule	Suppressed degradation of CUR and controlled drug release	Synthesis and self-assemble	1.05 um	^Citation68
Magnetic-response
Nanoparticle	1) Suppressed of PCNA, Bcl-xL, Mcl-1, MUC1, Collagen I and enhanced membrane β-catenin expression; 2) Improved serum bioavailability (2.5-fold)	Water-dispersible multi-layer synthesis approach	10.5±0.54 nm	^Citation34
	Sustained-release	Modified co-precipitation	100 nm	^Citation87
	Showed high stability, well-tolerated by mammalian cells and MRI relaxation properties	Ultrasonic dispersion and incubation chelation method	13 ± 4 nm	^Citation91
	Displayed strong anticancer on MDA-MB-231 cancer cells and superior magnetic resonance imaging characteristics	Modified co-precipitation and injection method	123 nm	^Citation92
Functional particle	Significantly enhanced the cellular uptake and better antiproliferative effect on the C6 glioma cell and HeLa cells	Co-precipitation, dispersion and synthesis methods	117 nm	^Citation94
	1) pH sensitive release, high loading capacity and hemocompatibility of CUR;2) Enhanced uptake and antiproliferation for MCF-7 breast cancer cell	Chemical co-precipitation method and molecular modified	195 and 240 nm	^Citation95
	1) improved the solubility (216 µg/mL), stability and bioavailability of CUR; 2) Suppressed the growth of Caco-2 cells (CC50=65 µg/mL)	Ice bath sonication and precipitation method	10 µm	^Citation97
Liposome	Magnetic heating controlled drug release by high-frequency magnetic field exposure; efficiently internalized into the cellular compartment and killed MCF-7 cells	Thin-film hydration method followed by extrusion techniques	120–140 nm	^Citation99
Microsphere	Showed controllable particle size and possessed good magnetic mobility	Water-in-oil-in-water method	16–207 µm	^Citation100
	Induced HeLa cancer cells death through magnetocalorific effect	Solvent evaporation method	75 nm	^Citation101
Hydrogel	Cardioprotective effects against dox-induced cardiac toxicity in rat cardiomyocyte cell lines	Emulsion polymerization and synthesis method	18–23 nm	^Citation105
Thermo-sensitive
Polymer gel	Improved targeting and bioavailability in the brain	Solvent injection method	–	^Citation108
	Temperature controlled release performance	Emulsion polymerization	180 nm	^Citation109
	Significantly prolong retention time in solid tumors	Solvent injection method	-	^Citation110
Liposomal-based gel	Showed better skin permeation in vitro and significant anti-inflammatory effect in auricle edemas mice	Emulsion evaporation-solidification at low temperature	263.9 nm	^Citation112
	Reduced toxicity of CUR and enhanced anti-tumor activity in tumor-bearing BALB/c mice	Thin-film rehydration method	950 nm	^Citation113
Micelle-based gel	1) Inhibited tumor growth and metastasis, and prolonged survival of tumor-bearing mice; 2) Showed lower proliferation activity, more apoptotic cells, and fewer microvessels; 3) Showed higher AUC and longer t1/2.	Dispersion method	27.1 nm	^Citation117
	Showed nano-scale size, low critical micelle concentration (0.0113–0.0144 mg/mL), high drug loading (20.4%) and stability (remain stable over 1 month)	Self-assembly and solvent evaporation/film hydration method	47.5–88.2 nm	^Citation118

Abbreviation: CUR, curcumin.

Figure 2 Physicochemical targeting preparations of Curcumin.

Figure 3 Schematic transition of CUR into physicochemical targeting preparations.

Table 2 The Trigger/Targeting Carries and Preparation Method of CUR-Loaded Physicochemical Targeting Preparations

Types	Trigger/Targeting Carries	Ref.
pH-sensitive	1) N-(3-Aminopropyl)imidazole-cholesterol (IM-Chol)	^Citation40
	2) A new endosomal cationic lipid consisted of glutamic acid backbone-based cationic amphiphiles	^Citation41
	3) Poly(isoprene-b-acrylic acid) copolymer (pI-pAA)	^Citation42
	4) Eudragit^®S100	^Citation43^–^Citation47,Citation66
	5) Chitosan and fucoidan	^Citation48
	6) Functionalized dendritic mesoporous silica	^Citation49
	7) Tannic acid-Fe(III) complex	^Citation50
	8) Chitosan and folate	^Citation51
	9) D-α-tocopheryl polyethylene glycol 1000-block-poly(β-amino ester) (TPGS-PAE copolymers)	^Citation52
	10) PEG2000-DOX	^Citation53
	11) Dox-oxidized sodium alginate (Dox-OSA)	^Citation54
	12) Zn(II)-CUR	^Citation55
	13) Amphiphilic N-benzyl-N,O-succinyl chitosan (BSCS)	^Citation57
	14) Poly(3-caprolactone)-block-poly(diethylaminoethyl methacrylate)-block-poly(sulfobetaine methacrylate) (PCL-PDEA-PSBMA)	^Citation58,Citation59
	15) Poly(l-histidine)-poly(D,L-lactide-co-glycolide)-poly(ethylene glycol)-poly(D,L-lactide-co-glycolide)-poly(l-histidine) (PHis-PLA-PEG-PLA-Phis) and a folate targeting ligand	^Citation60
	16) CUR-dextran	^Citation61
	17) Poloxam 188-Cis-CUR conjugate	^Citation62
	18) mPEG-poly(lactic acid)-CUR and mPEG-poly(lactic acid)-hydrazone-CUR (mPEG-PLA-CUR and mPEG-PLA-Hydr-CUR)	^Citation63
	19) mPEG-PLA-tris(hydroxymethyl)aminomethane-CUR (mPEG-PLA-Tris-CUR)	^Citation64
	20) mPEG-Chitosan-Ketal (PCK)	^Citation65
	21) Poly(butyl-methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl-methacrylate) (Eudragit^® EPO)	^Citation67
	22) Silica particles and poly(L-lysine)	^Citation68
	23) β-CD	^Citation96
	24) Pectin maleate	^Citation97
Magnetic	1) Oleic acid-modified iron oxide nanoparticles and NH2-PEG3500-T7	^Citation35
	2) Magnetic ferrite	^Citation34,Citation85–Citation87,Citation89–Citation97,Citation99–Citation102,Citation105
Thermo-sensitive	1) N-isopropyl acrylamide	^Citation97
	2) Poloxamer 407	^Citation107,Citation108,Citation110^–^Citation112
	3) Poly(N-vinylcaprolactam-co-hydroxyl ethyl ethacrylate)	^Citation109
	4) N-cholesteryl hemisuccinate-O-sulfate chitosan	^Citation113
	(5) Poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) copolymer	^Citation117
	6) Poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide)-b-poly(L-lactide)-b- poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide)	^Citation118

Abbreviations: CUR, curcumin; T7, human transferrin receptor-binding peptide T7.

Figure 4 Schematic representation of liposomal coating with Eudragit^@ S100 by the pH jump method.

Notes: Reprinted with permission from De LV, Milano F, Mancini E, et al. Encapsulation of curcumin-loaded liposomes for colonic drug delivery in a pH-responsive polymer cluster using a pH-driven and organic solvent-free process. Molecules. 2018;23(4):739. Copyright (2018) Multidisciplinary Digital Publishing Institute, Creative Common CC BY license.⁴³

Figure 5 Representative ex vivo images of tumor and main organs (heart, liver, spleen, lung, and kidney) after administration of DOX and PEG-Dox-CUR NPs.

Reprinted from Zhang Y, Yang C, Wang W, et al. Co-delivery of doxorubicin and  curcumin by pH-sensitive prodrug nanoparticle for combinationtherapy of cancer. Sci Rep. 2016;6(1):21225. This work is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/). ⁵⁵

Figure 6 Evaluation of experimental colitis in the colon of mice in (A) control group (severe lesions and inflammation), (B) CUR-treated group (moderate lesions), and (C) CUR microsphere-treated group (mild lesions).

Reprinted with permission from Sareen R, Jain N, Rajkumari A, et al. pH triggered delivery of curcumin from Eudragit-coated chitosan microspheres for inflammatory bowel disease: characterization and pharmacodynamic evaluation. Drug Delivery. 2016;23(1):55–62. Copyright (2016) Taylor & Francis Ltd (http://www.tandfonline.com).⁷⁴

Figure 7 Representative confocal images of (A) nano-Fe₃O₄-coated with CUR on SKOV-3, and (B) nano-Fe₃O₄-coated with CUR on SKOV-3 enhanced by magnetic field (Blue cells nuclei are labeled with DAPI, green nano-Fe₃O₄ are labeled with FITC (DXS-FITC), and red actin filaments are labeled with phalloidin-TRITC).

Notes: Reprinted with permission from Mancarella S, Greco V, Baldassarre F, et al. Polymer-coated magnetic nanoparticles for curcumin delivery to cancer cells. Macromol Biosci. 2015;15(10):1365–1374. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.⁹³

Abbreviations: CUR, Curcumin; DAPI, 4',6-diamidino-2-phenylindole FITC (DXS-FITC), Fluorescein isothiocyanate-dextran.

Ju L, Cailin F, Wenlan W, et al. Preparation and properties evaluation of a novel pH-sensitive liposomes based on imidazole-modified cholesterol derivatives. Int J Pharm. 2016;518(1–2):213–219. doi:10.1016/j.ijpharm.2016.11.04427889588

 PubMedGoogle Scholar

Moku G, Gulla SK, Nimmu NV, et al. Delivering anti-cancer drugs with endosomal pH-sensitive anti-cancer liposomes. Biomater Sci. 2016;4(4):627–638. doi:10.1039/C5BM00479A26806172

 PubMed Web of Science ®Google Scholar

Jelezova I, Drakalska E, Momekova D, et al. Curcumin loaded pH-sensitive hybrid lipid/block copolymer nanosized drug delivery systems. Eur J Pharm Sci. 2015;78:67–78. doi:10.1016/j.ejps.2015.07.00526159739

 PubMed Web of Science ®Google Scholar

De LV, Milano F, Mancini E, et al. Encapsulation of curcumin-loaded liposomes for colonic drug delivery in a pH-responsive polymer cluster using a pH-driven and organic solvent-free process. Molecules. 2018;23(4):739. doi:10.3390/molecules23040739

 PubMed Web of Science ®Google Scholar

Cui Y, Zhang M, Zeng F, Jin HY, Xu Q, Huang YZ. Dual-targeting magnetic PLGA nanoparticles for codelivery of paclitaxel and curcumin for brain tumor therapy. Acs Appl Mater Inter. 2016;8(47):32159–32169. doi:10.1021/acsami.6b10175

 PubMed Web of Science ®Google Scholar

Gugulothu D, Kulkarni A, Patravale V, et al. pH-sensitive nanoparticles of curcumin–celecoxib combination: evaluating drug synergy in ulcerative colitis model. J Pharm Sci. 2014;103(2):687–696. doi:10.1002/jps.2382824375287

 PubMed Web of Science ®Google Scholar

Wahlstrom B, Blennow G. A study on the fate of curcumin in the rat. Acta Pharmacol Toxicol. 1978;43(2):86–92. doi:10.1111/j.1600-0773.1978.tb02240.x

 PubMedGoogle Scholar

Beloqui A, Coco R, Memvanga PB, et al. pH-sensitive nanoparticles for colonic delivery of curcumin in inflammatory bowel disease. Int J Pharm. 2014;473(1–2):203–212.25014369

 PubMed Web of Science ®Google Scholar

Prajakta D, Ratnesh J, Chandan K, et al. Curcumin loaded pH-sensitive nanoparticles for the treatment of colon cancer. J Biomed Nanotechnol. 2009;5(5):445–455. doi:10.1166/jbn.2009.103820201417

 PubMed Web of Science ®Google Scholar

Abouaitah KE, Farghali AA, Swiderska-Sroda A, et al. pH-controlled release system for curcumin based on functionalized dendritic mesoporous silica nanoparticles. J Nanomed Nanotechnol. 2016;7(1):351.

 Google Scholar

Kim S, Philippot S, Fontanay S, et al. pH- and glutathione-responsive release of curcumin from mesoporous silica nanoparticles coated using tannic acid-Fe(III) complex. RSC Adv. 2015;5(110):90550–90558. doi:10.1039/C5RA16004A

 Web of Science ®Google Scholar

Ishihara T, Takeda M, Sakamoto H, et al. Accelerated blood clearance phenomenon upon repeated injection of PEG-modified PLA-nanoparticles. Pharm Res. 2009;26(10):2270–2279. doi:10.1007/s11095-009-9943-x19633820

 PubMed Web of Science ®Google Scholar

Gao C, Tang F, Gong G, et al. pH-Responsive prodrug nanoparticles based on a sodium alginate derivative for selective co-release of doxorubicin and curcumin into tumor cells. Nanoscale. 2017;9(34):12533. doi:10.1039/C7NR03611F28819666

 PubMed Web of Science ®Google Scholar

Wang DS, Zhou YX, Li CW, et al. Recent progress in research of pH-sensitive polymeric micelles as drug delivery system. Chin J New Drugs. 2016;25(19):2218–2224.

 Google Scholar

Sajomsang W, Gonil P, Saesoo S, et al. Synthesis and anticervical cancer activity of novel pH responsive micelles for oral curcumin delivery. Int J Pharm. 2014;477(1–2):261–272. doi:10.1016/j.ijpharm.2014.10.04225455774

 PubMedGoogle Scholar

Szakacs G, Paterson JK, Ludwig JA, Booth-Genthe C, Gottesman MM. Targeting multidrug resistance in cancer. Nat Rev Drug Discov. 2006;5(3):219–234.16518375

 PubMed Web of Science ®Google Scholar

Alvarez AI, Real R, Pérez MG, Prieto JG, Merino G. Modulation of the activity of ABC transporters (P-glycoprotein, MRP2, BCRP) by flavonoids and drug response. J Pharm Sci. 2010;99(2):598–617. doi:10.1002/jps.2185119544374

 PubMed Web of Science ®Google Scholar

Evers R, Kool M, Smith AJ, van Deemter L, de Haas M, Borst P. Inhibitory effect of the reversal agents V-104, GF120918 and Pluronic L61 on MDR1 Pgp-, MRP1- and MRP2-mediated transport. Br J Cancer. 2000;83(3):366–374. doi:10.1054/bjoc.2000.126010917553

 PubMed Web of Science ®Google Scholar

Yallapu MM, Ebeling MC, Khan S, et al. Novel curcumin-loaded magnetic nanoparticles for pancreatic cancer treatment. Mol Cancer Ther. 2013;12(8):1471–1480. doi:10.1158/1535-7163.MCT-12-122723704793

 PubMed Web of Science ®Google Scholar

Sideris S, Aoun F, Zanaty M, et al. Efficacy of weekly paclitaxel treatment as a single agent chemotherapy following first-line cisplatin treatment in urothelial bladder cancer. Mol Clin Oncol. 2016;4(6):1063–1067. doi:10.3892/mco.2016.82127284445

 PubMedGoogle Scholar

Zhou Q, Ye M, Lu Y, et al. Curcumin improves the tumoricidal effect of mitomycin C by suppressing ABCG2 expression in stem cell-like breast cancer cells. PLoS One. 2015;10(8):e0136694. doi:10.1371/journal.pone.013669426305906

 PubMed Web of Science ®Google Scholar

Talekar M, Ouyang Q, Goldberg MS, et al. Cosilencing of PKM-2 and MDR-1 sensitizes multidrug-resistant ovarian cancer cells to paclitaxel in a murine model of ovarian cancer. Mol Cancer Ther. 2015;14(7):1521–1531. doi:10.1158/1535-7163.MCT-15-010025964202

 PubMed Web of Science ®Google Scholar

Chin SF, Iyer KS, Saunders M, et al. Encapsulation and sustained release of curcumin using superparamagnetic silica reservoirs. Chem-Eur J. 2010;15(23):5661–5665. doi:10.1002/chem.200802747

 Web of Science ®Google Scholar

Silambarasi T, Latha S. Formulation and evaluation of curcumin loaded magnetic nanoparticles for cancer therapy. Int J Pharm Sci & Res. 2012;3(5):1–16.

 Google Scholar

Cheng KK, Wang YX, Chow AHL, et al. Amyloid plaques binding curcumin conjugated magnetic nanoparticles for diagnosis in Alzheimer’s disease TG2576 mice. Alzheimers Dement. 2014;10(4):152–153. doi:10.1016/j.jalz.2014.04.12223954029

 PubMedGoogle Scholar

Magro M, Campos R, Baratella D, et al. A magnetically drivable nanovehicle for curcumin with antioxidant capacity and MRI relaxation properties. Chemistry. 2015;20(37):11913–11920. doi:10.1002/chem.201402820

 Web of Science ®Google Scholar

Yallapu MM, Othman SF, Curtis ET, et al. Curcumin-loaded magnetic nanoparticles for breast cancer therapeutics and imaging applications. Int J Nanomed. 2012;7(1):1761–1779.

 PubMedGoogle Scholar

Salem M. Curcumin-loaded magnetic nanoaggregates conjugated with folic acid for targeted cancer treatment. Electronic Thesis Dissertation Repository. 2014;2206.

 Google Scholar

Almeida EAMS, Bellettini IC, Garcia FP, et al. Curcumin-loaded dual pH- and thermo-responsive magnetic microcarriers based on pectin maleate for drug delivery. Carbohyd Polym. 2017;171:259–266. doi:10.1016/j.carbpol.2017.05.034

 PubMed Web of Science ®Google Scholar

Hu L, Huang M, Wang J, et al. Preparation of magnetic poly(lactic-co-glycolic acid) microspheres with a controllable particle size based on a composite emulsion and their release properties for curcumin loading. J Appl Polym Sci. 2016;133(16):43317. doi:10.1002/app.43317

 Web of Science ®Google Scholar

Kini S, Bahadur D, Panda D. Magnetic PLGA nanospheres: a dual therapy for cancer. Ieee T Magn. 2011;47(10):2882–2886. doi:10.1109/TMAG.2011.2158403

 Web of Science ®Google Scholar

Hu RL, Ke XF, Jiang H, et al. Effect of interleukin-2 treatment combined with magnetic fluid hyperthermiaon lewis lung cancer-bearing mice. Biomed Rep. 2016;50(1):59–62. doi:10.3892/br.2015.540

 Google Scholar

Srivastava G, Mehta JL. Currying the heart: curcumin and cardioprotection. J Cardiovasc Pharmacol Ther. 2009;14(1):22–27. doi:10.1177/107424840832960819153099

 PubMed Web of Science ®Google Scholar

Namdari M, Eatemadi A. Cardioprotective effects of curcumin-loaded magnetic hydrogel nanocomposite (nanocurcumin) against doxorubicin-induced cardiac toxicity in rat cardiomyocyte cell lines. Artif Cell Nanomed B. 2017;45(4):731–739. doi:10.1080/21691401.2016.1261033

 PubMed Web of Science ®Google Scholar

Sudhakar K, Rao KM, Subha MCS, et al. Temperature-responsive poly(-vinylcaprolactam-co-hydroxyethyl methacrylate) nanogels for controlled release studies of curcumin. Des Monomers Polym. 2015;18(8):705–713. doi:10.1080/15685551.2015.1070497

 Web of Science ®Google Scholar

Gao M, Bao X, Lei AN, et al. Retention time of curcumin thermosensitive hydrogels for injection in solid tumor. China Pharm. 2012;23(3):206–208.

 Google Scholar

Huang YC, Lam UI. Chitosan/fucoidan pH sensitive nanoparticles for oral delivery system. J Chin Chem Soc. 2011;58(6):779–785. doi:10.1002/jccs.201190121

 Web of Science ®Google Scholar

Daryasari MP, Akhgar MR, Mamashli F, et al. Chitosan-folate coated mesoporous silica nanoparticles as a smart and pH-sensitive system for curcumin delivery. RSC Adv. 2016;6(107):105578–105588. doi:10.1039/C6RA23182A

 Web of Science ®Google Scholar

Gao Y, Li Y, Li Y, et al. PSMA-mediated endosome escape-accelerating polymeric micelles for targeted therapy of prostate cancer and the real time tracing of their intracellular trafficking. Nanoscale. 2014;7(2):597–612. doi:10.1039/C4NR05738D

 Web of Science ®Google Scholar

Zhang J, Li J, Shi Z, et al. pH-sensitive polymeric nanoparticles for co-delivery of doxorubicin and curcumin to treat cancer via enhanced pro-apoptotic and anti-angiogenic activities. Acta Biomater. 2017;58:349–364. doi:10.1016/j.actbio.2017.04.02928455219

 PubMed Web of Science ®Google Scholar

Zhang Y, Yang C, Wang W, et al. Co-delivery of doxorubicin and curcumin by pH-sensitive prodrug nanoparticle for combination therapy of cancer. Sci Rep. 2016;6(1):21225. doi:10.1038/srep2122526876480

 PubMedGoogle Scholar

Xing ZH, Wei JH, Cheang TY, et al. Bifunctional pH-sensitive Zn(II)-curcumin nanoparticles/siRNA effectively inhibit growth of human bladder cancer cells. J Mater Chem B. 2014;2(18):2714–2724. doi:10.1039/c3tb21625j32261437

 PubMed Web of Science ®Google Scholar

Zhai S, Ma Y, Chen Y, et al. Synthesis of an amphiphilic block copolymer containing zwitterionic sulfobetaine as a novel pH-sensitive drug carrier. Polym Chem. 2014;5(4):1285–1297.

 Web of Science ®Google Scholar

Wu Z, Cai M, Xie X, et al. The effect of architecture/composition on the pH sensitive micelle properties and in vivo study of curcuminin-loaded micelles containing sulfobetaines. RSC Adv. 2015;5(129):106989–107000. doi:10.1039/C5RA20847E

 Web of Science ®Google Scholar

Wei H, Shi H, Qiao M, et al. pH-sensitive micelles for the intracellular co-delivery of curcumin and Pluronic L61 unimers for synergistic reversal effect of multidrug resistance. Sci Rep. 2017;7:42465. doi:10.1038/srep4246528195164

 PubMed Web of Science ®Google Scholar

Plasschaert SLA, de Bont ESJM, Boezen M, et al. Expression of multidrug resistance-associated proteins predicts prognosis in childhood and adult acute lymphoblastic leukemia. Clin Cancer Res. 2005;11(24 Pt 1):8661–8668. doi:10.1158/1078-0432.CCR-05-109616361551

 PubMed Web of Science ®Google Scholar

Latorre M, Rinaldi C. Applications of magnetic nanoparticles in medicine: magnetic fluid hyperthermia. P R Health Sci J. 2009;28(3):227–238.19715115

 PubMed Web of Science ®Google Scholar

Kasai H, Kawai K, Shiraishi T, et al. Effects of Fe3O4 Magnetic Nanoparticles on A549 Cells. Int J Mol Sci. 2013;14(8):15546–15560. doi:10.3390/ijms14081554623892599

 PubMed Web of Science ®Google Scholar

Meador CB, Jin H, De SE, et al. Optimizing the sequence of anti-EGFR targeted therapy in EGFR-mutant lung cancer. Mol Cancer Ther. 2015;14(2):542–552. doi:10.1158/1535-7163.MCT-14-072325477325

 PubMed Web of Science ®Google Scholar

Manju S, Sharma CP, Sreenivasan K. Targeted coadministration of sparingly soluble paclitaxel and curcumin into cancer cells by surface engineered magnetic nanoparticles. J Mater Chem. 2011;21(39):15708–15717. doi:10.1039/c1jm12528a

 Web of Science ®Google Scholar

Hardiansyah A, Yang MC, Liu TY, et al. Hydrophobic drug-loaded PEGylated magnetic liposomes for drug-controlled release. Nanoscale Res Lett. 2017;12(1):355. doi:10.1186/s11671-017-2119-428525950

 PubMedGoogle Scholar

Sareen R, Jain N, Rajkumari A, et al. pH triggered delivery of curcumin from Eudragit-coated chitosan microspheres for inflammatory bowel disease: characterization and pharmacodynamic evaluation. Drug Deliv. 2016;23(1):55–62.

 Web of Science ®Google Scholar

Mancarella S, Greco V, Baldassarre F, et al. Polymer-coated magnetic nanoparticles for curcumin delivery to cancer cells. Macromol Biosci. 2015;15(10):1365–1374. doi:10.1002/mabi.20150014226085082

 PubMed Web of Science ®Google Scholar