Taguchi design optimization of curcumin loading in mesoporous silica nanoparticles with variable particle and pore sizes

Document Type : Original Article


1 Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz, Iran.

2 Pharmaceutical Nanotechnology Department, Shiraz School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

3 Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran.


Mesoporous silica nanoparticles (MSNs) have received a lot of attention due to their wide range of applications in the delivery of poorly soluble phytochemicals like curcumin (CUR). Given that pore diameter and particle size determine the specific surface area, as well as drug loading in mesoporous nanoparticles, in the present study, we developed MSNs with varying pore sizes to investigate their effects on CUR loading. Dynamic light scattering (DLS), field-emission- scanning electron microscopy (FE-SEM), and Brunauer-Emmett-Teller (BET) analyses were used to characterize the MSNs. CUR was loaded into MSNs using solvent evaporation method, and the drug loading was determined using UV spectroscopy. Results revealed that the MSN synthesis condition had a significant effect on pore size and particle diameter. According to FE-SEM micrographs, MSNs had a nearly spherical shape. DLS results indicated particle sizes ranging from 25 to 100 nm. According to the BET findings, pore size and specific surface area varied in range of 4 - 8 nm and of 570 - 1180 m2/g, respectively. In addition, CUR loading efficiency and loaded amount were 75% and 33% in optimal conditions, respectively. These findings supported the use of MSNs to load and deliver CUR as a poorly soluble drug in a variety of pathophysiological conditions.
Keywords: Mesoporous silica nanoparticles, Pore size, Particle size, Surface area, Drug loading, Curcumin.
Please cite this article as: Mina Shafiee, Samira Sadat Abolmaali, Mozhgan Abedanzadeh, Ali Mohammad Tamaddon. Taguchi design optimization of curcumin loading in mesoporous silica nanoparticles with variable particle and pore sizes. Trends in Pharmaceutical Sciences. 2022;8(3):155-164. doi: 10.30476/TIPS.2022.95646.1150


1.    Yallapu MM, Nagesh PK, Jaggi M, Chauhan SC. Therapeutic Applications of Curcumin Nanoformulations. AAPS J. 2015 Nov;17(6):1341-56. doi: 10.1208/s12248-015-9811-z. Epub 2015 Sep 3. PMID: 26335307; PMCID: PMC4627456.
2.    Karewicz A, Bielska D, Gzyl-Malcher B, Kepczynski M, Lach R, Nowakowska M. Interaction of curcumin with lipid monolayers and liposomal bilayers. Colloids Surf B Biointerfaces. 2011 Nov 1;88(1):231-9. doi: 10.1016/j.colsurfb.2011.06.037. Epub 2011 Jul 1. PMID: 21778041.
3.    Abedanzadeh, M., et al., Curcumin loaded polymeric micelles of variable hydrophobic lengths by RAFT polymerization: Preparation and in-vitro characterization. J Drug Deliv Sci Technol. 2020. 58: p. 101793.
4.    Gong C, Wu Q, Wang Y, Zhang D, Luo F, Zhao X, Wei Y, Qian Z. A biodegradable hydrogel system containing curcumin encapsulated in micelles for cutaneous wound healing. Biomaterials. 2013 Sep;34(27):6377-87. doi: 10.1016/j.biomaterials.2013.05.005. Epub 2013 May 29. PMID: 23726229.
5.    Parvathy, K., P. Negi, and P. Srinivas, Curcumin–amino acid conjugates: synthesis, antioxidant and antimutagenic attributes. Food Chem. 2010. 120(2): 523-30.
6.    Nandiyanto ABD, Kim S-G, Iskandar F, Okuyama K. Synthesis of spherical mesoporous silica nanoparticles with nanometer-size controllable pores and outer diameters. Microporous Mesoporous Mater. 2009;120(3):447-53. 
7.    Iskandar F, Lenggoro IW, Kim TO, Nakao N, Shimada M, Okuyama K. Fabrication and characterization of SiO2 particles generated by spray method for standards aerosol. J Chem Eng Japan. 2001;34(10):1285-92.
8.    Kao K, Mou C. Pore-expanded mesoporous silica nanoparticles with alkanes/ethanol as pore expanding agent. Microporous Mesoporous Mater. 2013;169:7-15.
9.    Kilpeläinen M, Riikonen J, Vlasova MA, Huotari A, Lehto VP, Salonen J, et al. In vivo delivery of a peptide, ghrelin antagonist, with mesoporous silicon microparticles. J Control Release. 2009 Jul 20;137(2):166-70. doi: 10.1016/j.jconrel.2009.03.017. Epub 2009 Apr 2. PMID: 19345247.
10.    Chen JF, Ding HM, Wang JX, Shao L. Preparation and characterization of porous hollow silica nanoparticles for drug delivery application. Biomaterials. 2004 Feb;25(4):723-7. doi: 10.1016/s0142-9612(03)00566-0. PMID: 14607511.
11.    Vasconcelos T, Sarmento B, Costa P. Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs. Drug Discov Today. 2007 Dec;12(23-24):1068-75. doi: 10.1016/j.drudis.2007.09.005. Epub 2007 Oct 30. PMID: 18061887.
12.    Sachs-Barrable K, Lee SD, Wasan EK, Thornton SJ, Wasan KM. Enhancing drug absorption using lipids: a case study presenting the development and pharmacological evaluation of a novel lipid-based oral amphotericin B formulation for the treatment of systemic fungal infections. Adv Drug Deliv Rev. 2008 Mar 17;60(6):692-701. doi: 10.1016/j.addr.2007.08.042. Epub 2007 Nov 5. Erratum in: Adv Drug Deliv Rev. 2008 Dec 14;60(15):1675. PMID: 18053611.
13.    Dinda AK, Prashant CK, Naqvi S, Unnithan J, Samim M, Maitra A. Curcumin loaded organically modified silica (ORMOSIL) nanoparticle; a novel agent for cancer therapy. Int J Nanotechnol. 2012;9(10):862.
14.    Kim S, Stébé M,a Blina J, Pasc A. pH-controlled delivery of curcumin from a compartmentalized solid lipid nanoparticle@ mesostructured silica matrix. J Mater Chem B. 2014;2(45):7910-17.
15.    Patra, D. and F. Sleem. A new method for pH triggered curcumin release by applying poly (l-lysine) mediated nanoparticle-congregation. Anal.Chim Acta. 2013;795:60-8.
16.    Li N, Wang Z, Zhang Y, Zhang K, Xie J, Liu Y, et al. Curcumin-loaded redox-responsive mesoporous silica nanoparticles for targeted breast cancer therapy. Artif Cells Nanomed Biotechnol. 2018;46(sup2):921-935. doi: 10.1080/21691401.2018.1473412. Epub 2018 May 23. PMID: 29790797.
17.    Lv Y, Li J, Chen H, Bai Y, Zhang L. Glycyrrhetinic acid-functionalized mesoporous silica nanoparticles as hepatocellular carcinoma-targeted drug carrier. Int J Nanomedicine. 2017 Jun 12;12:4361-4370. doi: 10.2147/IJN.S135626. PMID: 28652738; PMCID: PMC5476610.
18.    Radhakrishnan K,  Tripathy J, Datey,bc   Chakravortty A.D, RaichurA.M. Mesoporous silica–chondroitin sulphate hybrid nanoparticles for targeted and bio-responsive drug delivery. New J  Chem. 2015;39(3):1754-60.
19.    Sun X, Wang N, Yang LY, Ouyang XK, Huang F. Folic Acid and PEI Modified Mesoporous Silica for Targeted Delivery of Curcumin. Pharmaceutics. 2019 Aug 23;11(9):430. doi: 10.3390/pharmaceutics11090430. Erratum in: Pharmaceutics. 2020 Jul 03;12(7): PMID: 31450762; PMCID: PMC6781278.
20.    Xu X, Lü S, Gao C, Feng C, Wu C, Bai X, et al. Self-fluorescent and stimuli-responsive mesoporous silica nanoparticles using a double-role curcumin gatekeeper for drug delivery. Chem Eng J. 2016;300:185-92.
21.    Zhang Y, Zhi Z, Jiang T, Zhang J, Wang Z, Wang S. Spherical mesoporous silica nanoparticles for loading and release of the poorly water-soluble drug telmisartan. J Control Release. 2010 Aug 3;145(3):257-63. doi: 10.1016/j.jconrel.2010.04.029. Epub 2010 May 5. PMID: 20450945.
22.    Shafiee M, Abolmaali S, Abedanzadeh M, Abedi M, Tamaddon A. Synthesis of Pore-Size-Tunable Mesoporous Silica Nanoparticles by Simultaneous Sol-Gel and Radical Polymerization to Enhance Silibinin Dissolution. Iran J Med Sci. 2021 Nov;46(6):475-486. doi: 10.30476/ijms.2020.86173.1595. PMID: 34840388; PMCID: PMC8611219.
23.    Shafiee M, Abolmaali SS, Tamaddon AM, Abedanzadeh M, Abedi M. One-pot synthesis of poly (alkyl methacrylate)-functionalized mesoporous silica hybrid nanocomposites for microencapsulation of poorly soluble phytochemicals. Colloids Interface Sci Commun. 2020;37:100298.
24.    Sreelola V, Sailaja AK, Pharmacy M.  Preparation and characterisation of ibuprofen loaded polymeric nanoparticles by solvent evaporation technique. Int J Pharm Pharm Sci. 2014;6(8):416-421.
25.    Freidus LG, Kumar P, Marimuthu T, Pradeep P, Choonara YE. Theranostic Mesoporous Silica Nanoparticles Loaded With a Curcumin-Naphthoquinone Conjugate for Potential Cancer Intervention. Front Mol Biosci. 2021 May 20;8:670792. doi: 10.3389/fmolb.2021.670792. PMID: 34095225; PMCID: PMC8173119.
26.    Taebnia N, Morshedi D, Yaghmaei S, Aliakbari F, Rahimi F, Arpanaei A. Curcumin-loaded amine-functionalized mesoporous silica nanoparticles inhibit α-synuclein fibrillation and reduce its cytotoxicity-associated effects. Langmuir. 2016;32(50):13394-402.
27.    Basavarajappa S, Chandramohan G, Davim JP. Application of Taguchi techniques to study dry sliding wear behaviour of metal matrix composites. Mater Des. 2007;28(4):1393-8.
28.    Wang Y, Shan Y, Chen KZ, Gao L. Mesoporous Silica Nanoparticles with Controllable Pore Size: Preparation and Drug Release. AMR 2013;774-776:536-9.
29.    Abdous B, Sajjadi SM, Ma’mani L. β-Cyclodextrin modified mesoporous silica nanoparticles as a nano-carrier: Response surface methodology to investigate and optimize loading and release processes for curcumin delivery. 
J Appl Biomed. 2017;15(3):210-8.
30.    Bolouki A, Rashidi L, Vasheghani-Farahani E, Piravi-Vanak Z. Study of mesoporous silica nanoparticles as nanocarriers for sustained release of curcumin. Int J Nanosci Nanotechnol. 2015;11(3):139-46.
31.    Daryasari MP, Akhgar MR, Mamashli F, Bigdeli B, Khoobi M. Chitosan-folate coated mesoporous silica nanoparticles as a smart and pH-sensitive system for curcumin delivery. Rsc Advances. 2016;6(107):105578-88.
32.    Kuang G, Zhang Q, He S, Liu Y. Curcumin-loaded PEGylated mesoporous silica nanoparticles for effective photodynamic therapy. RSC advances. 2020;10(41):24624-30.
33.    Ma'mani L, Nikzad S, Kheiri-Manjili H, Al-Musawi S, Saeedi M, Askarlou S, et al. Curcumin-loaded guanidine functionalized PEGylated I3ad mesoporous silica nanoparticles KIT-6: practical strategy for the breast cancer therapy. Eur J Med Chem. 2014 Aug 18;83:646-54. doi: 10.1016/j.ejmech.2014.06.069. Epub 2014 Jun 28. PMID: 25014638.
34.    Elbialy NS, Aboushoushah SF, Sofi BF, Noorwali A. Multifunctional curcumin-loaded mesoporous silica nanoparticles for cancer chemoprevention and therapy. Microporous Mesoporous Mater. 2020;291:109540.
35.    Ghosh S, Dutta S, Sarkar A, Kundu M, Sil PC. Targeted delivery of curcumin in breast cancer cells via hyaluronic acid modified mesoporous silica nanoparticle to enhance anticancer efficiency. Colloids Surf B Biointerfaces. 2021 Jan;197:111404. doi: 10.1016/j.colsurfb.2020.111404. Epub 2020 Oct 25. PMID: 33142257.
36.    Kong ZL, Kuo HP, Johnson A, Wu LC, Chang KLB. Curcumin-Loaded Mesoporous Silica Nanoparticles Markedly Enhanced Cytotoxicity in Hepatocellular Carcinoma Cells. Int J Mol Sci. 2019 Jun 14;20(12):2918. doi: 10.3390/ijms20122918. PMID: 31207976; PMCID: PMC6628080.
37.    Yadav YC, Pattnaik S, Swain K. Curcumin loaded mesoporous silica nanoparticles: assessment of bioavailability and cardioprotective effect. Drug Dev Ind Pharm. 2019 Dec;45(12):1889-1895. doi: 10.1080/03639045.2019.1672717. Epub 2019 Oct 7. PMID: 31549866.
38.    Harini L, Srivastava S, Gnanakumar GP, Karthikeyan B, Ross C, Krishnakumar V, et al. An ingenious non-spherical mesoporous silica nanoparticle cargo with curcumin induces mitochondria-mediated apoptosis in breast cancer (MCF-7) cells. Oncotarget. 2019 Feb 5;10(11):1193-1208. doi: 10.18632/oncotarget.26623. PMID: 30838091; PMCID: PMC6383822.
39.    Mohebian Z, Babazadeh M, Zarghami N. In Vitro Efficacy of Curcumin-Loaded Amine-Functionalized Mesoporous Silica Nanoparticles against MCF-7 Breast Cancer Cells. Adv Pharm Bull. 2022.
40.    Mondal S, Ghosh S, Moulik SP. Stability of curcumin in different solvent and solution media: UV–visible and steady-state fluorescence spectral study. J Photochem Photobiol B, Biol 2016;158:212-8.
41.    Abedi M, Abolmaali SS, Abedanzadeh M, Borandeh S, Samani SM, Tamaddon AM. Citric acid functionalized silane coupling versus post-grafting strategy for dual pH and saline responsive delivery of cisplatin by Fe3O4/carboxyl functionalized mesoporous SiO2 hybrid nanoparticles: A-synthesis, physicochemical and biological characterization. Mater Sci Eng C. 2019;104:109922.
42.    Abedi M, Abolmaali SS, Abedanzadeh M, Farjadian F, Mohammadi Samani S, Tamaddon AM. Core-Shell Imidazoline-Functionalized Mesoporous Silica Superparamagnetic Hybrid Nanoparticles as a Potential Theranostic Agent for Controlled Delivery of Platinum(II) Compound. Int J Nanomedicine. 2020 Apr 20;15:2617-2631. doi: 10.2147/IJN.S245135. PMID: 32368044; PMCID: PMC7182466.
43.    Soleimanpour M, Tamaddon AM, Kadivar M, Abolmaali SS, Shekarchizadeh H. Fabrication of nanostructured mesoporous starch encapsulating soy-derived phytoestrogen (genistein) by well-tuned solvent exchange method. Int J Biol Macromol. 2020 Sep 15;159:1031-1047. doi: 10.1016/j.ijbiomac.2020.05.124. Epub 2020 May 19. PMID: 32439450.
44.    Mashayekhi S, Rasoulpoor S, Shabani S, Esmaeilizadeh N, Serati-Nouri H, Sheervalilou R, Pilehvar-Soltanahmadi Y. Curcumin-loaded mesoporous silica nanoparticles/nanofiber composites for supporting long-term proliferation and stemness preservation of adipose-derived stem cells. Int J Pharm. 2020 Sep 25;587:119656. doi: 10.1016/j.ijpharm.2020.119656. Epub 2020 Jul 18. PMID: 32687972.