In vivo Antiplasmodial Activity of Curcumin-Loaded Nanostructured Lipid Carriers

Author(s): Hamid Rashidzadeh, Mahsa Salimi, Somayeh Sadighian*, Kobra Rostamizadeh, Ali Ramazani*

Journal Name: Current Drug Delivery

Volume 16 , Issue 10 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Background: It has been shown that curcumin (Cur) has anti-plasmodial activity; however, its weak bioavailability, rapid metabolism, and limited chemical stability have restricted its application in clinical usages. Nanostructured lipid carriers (NLCs) are a type of Drug-Delivery Systems (DDSs) whose core matrix is composed of both solid and liquid lipids.

Objective: The aim of the current study was to prepare and characterize curcumin-loaded nanostructured lipid carriers (Cur-NLC) for malaria treatment.

Methods: For producing NLC, coconut oil and cetyl palmitate were selected as a liquid and solid lipid, respectively. In order to prepare the Cur-NLC, the microemulsion method was applied. General toxicity assay on Artemia salina as well as hemocompatibility was investigated. Anti-plasmodial activity was studied on mice infected with Plasmodium berghei.

Results: The NLCs mean particle size and Polydispersity Index (PI) were 145 nm and 0.3, respectively. Further, the zeta potential of the Cur-NLC was −25 mV. The NLCs indicated a pseudo-spherical shape observed via transmission electron microscopy (TEM). The loading capacity and encapsulation efficacy of the obtained Cur-NLC were 3.1 ± 0.015% and 74 ± 3.32%, respectively. In vitro, Cur release profiles showed a sustained-release pattern up to 5 days in the synthesized Cur-NLC. The results of in vivo antiplasmodial activity against P. berghei revealed that antimalarial activity of Cur-NLC was significantly higher compared with that of free Cur at the dose of 40 mg/kg/day.

Conclusion: The results of this study suggested that NLC would be used as a potential nanocarrier for the treatment of malaria.

Keywords: Nanostructured lipid carriers (NLCs), Curcumin, Malaria, Plasmodium berghei, Drug-Delivery Systems (DDSs), Polydispersity Index (PI).

Heller, L.E.; Roepe, P.D. Artemisinin-based antimalarial drug therapy: Molecular pharmacology and evolving resistance. Trop. Med. Infect. Dis., 2019, 4(2), pii: E89.
[] [PMID: 31167396]
Reddy, R.C.; Vatsala, P.G.; Keshamouni, V.G.; Padmanaban, G.; Rangarajan, P.N. Curcumin for malaria therapy. Biochem. Biophys. Res. Commun., 2005, 326(2), 472-474.
[] [PMID: 15582601]
Tiwari, S.K.; Agarwal, S.; Seth, B.; Yadav, A.; Nair, S.; Bhatnagar, P.; Karmakar, M.; Kumari, M.; Chauhan, L.K.S.; Patel, D.K.; Srivastava, V.; Singh, D.; Gupta, S.K.; Tripathi, A.; Chaturvedi, R.K.; Gupta, K.C. Curcumin-loaded nanoparticles potently induce adult neurogenesis and reverse cognitive deficits in Alzheimer’s disease model via canonical Wnt/β-catenin pathway. ACS Nano, 2014, 8(1), 76-103.
[] [PMID: 24467380]
Amanlou, N.; Parsa, M.; Rostamizadeh, K.; Sadighian, S.; Moghaddam, F. Enhanced cytotoxic activity of curcumin on cancer cell lines by incorporating into gold/chitosan nanogels. Mater. Chem. Phys., 2019, 226, 151-157.
Zangui, M.; Atkin, S.L.; Majeed, M.; Sahebkar, A. Current evidence and future perspectives for curcumin and its analogues as promising adjuncts to oxaliplatin: state-of-the-art. Pharmacol. Res., 2019, 141, 343-356.
[] [PMID: 30641277]
Javadi, S.; Rostamizadeh, K.; Hejazi, J.; Parsa, M.; Fathi, M. Curcumin mediated down-regulation of αV β3 integrin and up-regulation of pyruvate dehydrogenase kinase 4 (PDK4) in Erlotinib resistant SW480 colon cancer cells. Phytother. Res., 2018, 32(2), 355-364.
[] [PMID: 29168312]
Kanai, M.; Otsuka, Y.; Otsuka, K.; Sato, M.; Nishimura, T.; Mori, Y.; Kawaguchi, M.; Hatano, E.; Kodama, Y.; Matsumoto, S.; Murakami, Y.; Imaizumi, A.; Chiba, T.; Nishihira, J.; Shibata, H. A phase I study investigating the safety and pharmacokinetics of highly bioavailable curcumin (Theracurmin) in cancer patients. Cancer Chemother. Pharmacol., 2013, 71(6), 1521-1530.
[] [PMID: 23543271]
Hazzah, H.A.; Farid, R.M.; Nasra, M.M.; El-Massik, M.A.; Abdallah, O.Y. Lyophilized sponges loaded with curcumin solid lipid nanoparticles for buccal delivery: Development and characterization. Int. J. Pharm., 2015, 492(1-2), 248-257.
[] [PMID: 26189427]
Ramazani, A.; Abrvash, M.; Sadighian, S.; Rostamizadeh, K.; Fathi, M. Preparation and characterization of curcumin loaded gold/graphene oxide nanocomposite for potential breast cancer therapy. Res. Chem. Intermed., 2018, 44(12), 7891-7904.
Karami, Z.; Sadighian, S.; Rostamizadeh, K.; Parsa, M.; Rezaee, S. Naproxen conjugated mPEG-PCL micelles for dual triggered drug delivery. Mater. Sci. Eng. C, 2016, 61, 665-673.
[] [PMID: 26838895]
Karami, Z.; Sadighian, S.; Rostamizadeh, K.; Hosseini, S.H.; Rezaee, S.; Hamidi, M. Magnetic brain targeting of naproxen-loaded polymeric micelles: pharmacokinetics and biodistribution study. Mater. Sci. Eng. C, 2019, 100, 771-780.
[] [PMID: 30948114]
Franceschi, F.; Feregalli, B.; Togni, S.; Cornelli, U.; Giacomelli, L.; Eggenhoffner, R.; Belcaro, G. A novel phospholipid delivery system of curcumin (Meriva®) preserves muscular mass in healthy aging subjects. Eur. Rev. Med. Pharmacol. Sci., 2016, 20(4), 762-766.
[PMID: 26957282]
Muller, H.R.; Shegokar, R.; M, Keck. C. 20 years of lipid nanoparticles (SLN and NLC): Present state of development and industrial applications. Curr. Drug Discov. Technol., 2011, 8(3), 207-227.
[] [PMID: 21291409]
Sauvant, P.; Cansell, M.; Sassi, A.H.; Atgié, C. Vitamin A enrichment: Caution with encapsulation strategies used for food applications. Food Res. Int., 2012, 46(2), 469-479.
Selvamuthukumar, S.; Velmurugan, R. Nanostructured lipid carriers: A potential drug carrier for cancer chemotherapy. Lipids Health Dis., 2012, 11(1), 159.
[] [PMID: 23167765]
Madane, R.G.; Mahajan, H.S. Curcumin-loaded nanostructured lipid carriers (NLCs) for nasal administration: Design, characterization, and in vivo study. Drug Deliv., 2016, 23(4), 1326-1334.
[PMID: 25367836]
Wang, F.; Chen, J.; Dai, W.; He, Z.; Zhai, D.; Chen, W. Pharmacokinetic studies and anticancer activity of curcumin-loaded nanostructured lipid carriers. Acta Pharm., 2017, 67(3), 357-371.
[] [PMID: 28858837]
Padmanaban, G.; Rangarajan, P.N. Curcumin as an adjunct drug for infectious diseases. Trends Pharmacol. Sci., 2016, 37(1), 1-3.
[] [PMID: 26521094]
Anand, P.; Kunnumakkara, A.B.; Newman, R.A.; Aggarwal, B.B. Bioavailability of curcumin: Problems and promises. Mol. Pharm., 2007, 4(6), 807-818.
[] [PMID: 17999464]
Sangsen, Y.; Laochai, P.; Chotsathidchai, P.; Wiwattanapatapee, R. In Advanced materials research. Trans. Tech. Publ., 2015, 1060, 62-65.
Singh, S.K.; Dadhania, P.; Vuddanda, P.R.; Jain, A.; Velaga, S.; Singh, S. Intranasal delivery of asenapine loaded nanostructured lipid carriers: Formulation, characterization, pharmacokinetic and behavioural assessment. RSC Advances, 2016, 6(3), 2032-2045.
Chen, H.; Gao, J.; Wang, F.; Liang, W. Preparation, characterization and pharmacokinetics of liposomes-encapsulated cyclodextrins inclusion complexes for hydrophobic drugs. Drug Deliv., 2007, 14(4), 201-208.
[] [PMID: 17497352]
Aditya, N.P.; Shim, M.; Lee, I.; Lee, Y.; Im, M.H.; Ko, S. Curcumin and genistein coloaded nanostructured lipid carriers: In vitro digestion and antiprostate cancer activity. J. Agric. Food Chem., 2013, 61(8), 1878-1883.
[] [PMID: 23362941]
Rajabi, S.; Ramazani, A.; Hamidi, M.; Naji, T. Artemia salina as a model organism in toxicity assessment of nanoparticles. Daru, 2015, 23(1), 20.
[] [PMID: 25888940]
Finney, D.J. The adjustment for a natural response rate in probit analysis. Ann. Appl. Biol., 1949, 36(2), 187-195.
[] [PMID: 18151945]
Onambele, L.A.; Riepl, H.; Fischer, R.; Pradel, G.; Prokop, A.; Aminake, M.N. Synthesis and evaluation of the antiplasmodial activity of tryptanthrin derivatives. Int. J. Parasitol. Drugs Drug Resist., 2015, 5(2), 48-57.
[] [PMID: 25949928]
Ramazani, A.; Tavakolizadeh, M.; Ramazani, S.; Kheiri-Manjili, H.; Eskandari, M. Antiplasmodial property of Glycyrrhiza glabra traditionally used for malaria in Iran: Promising activity with high selectivity index for malaria. J. Arthropod Borne Dis., 2018, 12(2), 135-140.
[] [PMID: 30123807]
Ramazani, A.; Keramati, M.; Malvandi, H.; Danafar, H.; Kheiri Manjili, H. Preparation and in vivo evaluation of anti-plasmodial properties of artemisinin-loaded PCL-PEG-PCL nanoparticles. Pharm. Dev. Technol., 2018, 23(9), 911-920.
[] [PMID: 28851256]
Waknine-Grinberg, J.H.; McQuillan, J.A.; Hunt, N.; Ginsburg, H.; Golenser, J. Modulation of cerebral malaria by fasudil and other immune-modifying compounds. Exp. Parasitol., 2010, 125(2), 141-146.
[] [PMID: 20093114]
Lim, S-J.; Kim, C-K. Formulation parameters determining the physicochemical characteristics of solid lipid nanoparticles loaded with all-trans retinoic acid. Int. J. Pharm., 2002, 243(1-2), 135-146.
[] [PMID: 12176302]
Monopoli, M.P.; Walczyk, D.; Campbell, A.; Elia, G.; Lynch, I.; Bombelli, F.B.; Dawson, K.A. Physical-chemical aspects of protein corona: relevance to in vitro and in vivo biological impacts of nanoparticles. J. Am. Chem. Soc., 2011, 133(8), 2525-2534.
[] [PMID: 21288025]
Averina, E.S.; Müller, R.H.; Popov, D.V.; Radnaeva, L.D. Physical and chemical stability of nanostructured lipid drug carriers (NLC) based on natural lipids from Baikal region (Siberia, Russia). Pharmazie, 2011, 66(5), 348-356.
[PMID: 21699068]
Lakshmi, P.; Kumar, G. A review nanosuspension technology. Int. J. Pharm. Pharm. Sci., 2010, 2(4), 35-40.
Grynkiewicz, G.; Ślifirski, P. Curcumin and curcuminoids in quest for medicinal status. Acta Biochim. Pol., 2012, 59(2), 201-212.
[] [PMID: 22590694]
Gowthamarajan, K.; Singh, S.K. Dissolution testing for poorly soluble drugs: A continuing perspective. Dissolut. Technol., 2010, 17(3), 24-32.
Hu, F-Q.; Jiang, S-P.; Du, Y-Z.; Yuan, H.; Ye, Y-Q.; Zeng, S. Preparation and characterization of stearic acid nanostructured lipid carriers by solvent diffusion method in an aqueous system. Colloids Surf. B Biointerfaces, 2005, 45(3-4), 167-173.
[] [PMID: 16198092]
Teeranachaideekul, V.; Souto, E.B.; Junyaprasert, V.B.; Müller, R.H. Cetyl palmitate-based NLC for topical delivery of Coenzyme Q(10) - development, physicochemical characterization and in vitro release studies. Eur. J. Pharm. Biopharm., 2007, 67(1), 141-148.
[] [PMID: 17346953]
zur Mühlen, A.; zur Mühlen, E.; Niehus, H.; Mehnert, W. Atomic force microscopy studies of solid lipid nanoparticles. Pharm. Res., 1996, 13(9), 1411-1416.
[] [PMID: 8893284]
Sood, S.; Jawahar, N.; Jain, K.; Gowthamarajan, K.; Nainar Meyyanathan, S. Olanzapine loaded cationic solid lipid nanoparticles for improved oral bioavailability. Curr. Nanosci., 2013, 9(1), 26-34.
Meyer, B.N.; Ferrigni, N.R.; Putnam, J.E.; Jacobsen, L.B.; Nichols, D.E.; McLaughlin, J.L. Brine shrimp: A convenient general bioassay for active plant constituents. Planta Med., 1982, 45(5), 31-34.
[] [PMID: 17396775]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [923 - 930]
Pages: 8
DOI: 10.2174/1567201816666191029121036
Price: $65

Article Metrics

PDF: 28