Entrapped chemically synthesized gold nanoparticles combined with polyethylene glycol and chloroquine diphosphate as an improved antimalarial drug

Document Type: Research Paper


1 Biochemistry Department, Federal University of Technology, Bosso, Nigeria

2 Chemical Engineering Department, Federal University of Technology, Minna, Nigeria

3 Mechanical Engineering Department, Federal University of Technology, Minna, Nigeria

4 Chemistry Department, Federal University of Technology Minna, Nigeria


Objective(s): Drug delivery is an engineering technology to control the release and delivery of therapeutic agents to target organs, tissues, and cells. Metallic nanoparticles, such as gold nanoparticles (AuNPs) have exceptional properties which enable efficient drug transport into different cell types with reduced side effects and cytotoxicity to other tissues.
Materials and Methods: AuNPs were synthesized by adopting the Turkevich method to reduce tetra chloroauric (III) acid (HAuCl4) solution with sodium citrate. A factorial design of 24 was used to investigate the influence of temperature, stirring speed, and the volume of citrate and gold salt on the size of AuNPs synthesis. The produced chemical-AuNPs (CN-AuNPs) were characterized using ultraviolet-visible spectroscopy and dynamic light scattering (DLS) which was conjugated with polyethylene glycol (PEG) loaded with chloroquine diphosphate. The latter were characterized with transmission electron microscopy (TEM), Energy dispersive x-ray spectroscopy (EDS), selected area electron diffraction (SAED) patterns and Fourier transmission infrared spectroscopy. The antimalarial activities of the three formulations were tested on Plasmodium-infected mice. Moreover, the evaluation of curative potentials of the formulations was carried out via parasite counts. The anemic and pathological conditions of nano-encapsulation were investigated for their cytotoxicity level.
Results: The CN-AuNPs show surface plasmon resonance absorption ranging from 526 to 529 nm with smaller particle size at the lower citrate volume. The TEM image of CN-AuNPs with polyethylene glycol (PEG) and CN-AuNPs-PEG encapsulated with chloroquine diphosphate revealed spherical shape with EDS showing the appearance of gold (Au) at 2.0, 2.1, and 9.9 KeV. The SAED also revealed that the AuNPs were crystalline in nature. The in vitro time-dependent encapsulation release showed an extension of time release, compared to CN-AuNPs-PEG with parasitemia clearance at the same level of cytotoxicity.
Conclusion: Therefore, although improved activity of the CN-AuNPs-PEG encapsulating was achieved but its cytotoxicity still is a limitation.


1.Crompton PD, Moebius J, Portugal S, Waisberg M, Hart G, Garver LS, Miller LH, Barillas-Mury C, Pierce SK. Malaria Immunity in man and Mosquito: Insights Into unsolved mysteries of a deadly infectious disease. Annu Rev Immunol. 2014; 32: 157-187.
2.Talisuna AO, Nalunkuma‐Kazibwe A, Bakyaita N, Langi P, Mutabingwa TK, Watkins WW, Van Marck E, D’alessandro U, Egwang TG. Efficacy of sulphadoxine–pyrimethamine alone or combined with amodiaquine or chloroquine for the treatment of uncomplicated falciparum malaria in Ugandan children. Trop Med Int Health. 2004; 9(2): 222-229.
3.Nigussie D, Beyene T, Shah NA, Belew S. New Targets in Malaria Parasite Chemotherapy: A Review. Malaria Contr Elimination. 2015; S1:S1-007.
4.Singh R, Lillard JW Jr. Nanoparticle-based targeted drug delivery. Exp Mol Pathol. 2009; 86(3): 215–223.
5.Harish KK, Nagasamy V, Himangshu B, Anuttam K. Metallic Nanoparticle: A Review. Biomedical Journal of Scientific & Technical Research. 2018; 4(2)
6.Kumar A, BBM, Liang XJ. Gold nanoparticles: promising nanomaterials for the diagnosis of cancer and HIV/AIDS. J Nanomater. 2011; 2011: 1-17.
7.Almeida JPM, Chen AL, Foster A,Drezek R. In vivo biodistribution of nanoparticles. Nanomedicine(Lond). 2011; 6(5): 815-835.
8.Pooja D, Panyaram S, Kulhari H, Rachamalla SS, Sistla R. Xanthan gum stabilized gold nanoparticles: characterization, biocompatibility, stability and cytotoxicity. Carbohydr Polym. 2014; 110: 1-9.
9.Thakor AS, Jokerst J, Zavaleta C, Massoud TF, Gambhir SS. Gold nanoparticles: a revival in precious metal administration to patients. Nano Lett. 2011; 11(10): 4029–4036.
10.Kumar KP, Paul W, Sharma CP. Green synthesis of gold nanoparticles with Zingiber officinale extract: characterization and blood compatibility. Process Biochem. 2011; 46(10): 2007-2013.
11.Vilar G, Tulla-Puche J, Albericio F. Polymers and drug delivery systems. Curr Drug Deliv. 2012; 9(4): 367-394.
12.Markl D, Zeitler JA. A Review of Disintegration Mechanisms and Measurement Techniques. Pharm Res. 2017; 34(5): 890–917.
13.Kumari A, Yadav SK, Yadav SC. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf B Biointerfaces. 2010; 75(1): 1-18.
14.Li SD, Huang L. Stealth nanoparticles: high density but sheddable PEG is a key for tumor targeting. J Control Release. 2010; 145(3): 178.
15.Muller RH, Gohla S, Keck CM. State of the art of nanocrystals-special features production, nanotoxicology aspects and intracellular delivery. Eur J Pharm Biopharm. 2011; 78(1): 1-9.
16.Joshi P, Chakraborty S, Dey S, Shanker V, Ansari ZA, Singh SP. Binding of chloroquine-conjugated gold nanoparticles with bovine serum albumin. J Colloid Interface Sci. 2011; 355(2): 402-409.
17.Zhang X, Chibli H, Mielke R, Nadeau J. Ultrasmall gold-doxorubicin conjugates rapidly kill apoptosis-resistant cancer cells. Bioconjug Chem. 2011; 22(2): 235–243.
18.Movellan J, Urbán P, Moles E, Jesús M, Sierra T, Serrano JL, Fernandez-Busquets X. Amphiphilic dendritic derivatives as nanocarriers for the targeted delivery of antimalarial drugs. Biomaterials. 2014; 35(27): 7940-7950.
19.Urban P, Valle–Degado JJ, Mavro N, Marques J, Manfredi A, Rotman M, Ranucci E, Ferruti P, Fernàndez-Busquets X. Use of poly (amido amine) drug conjugates for the delivery of anti malarials to plasmodium. J Control Release. 2014; 177: 84-95.
20.Shittu KO, Bankole MT, Abdulkareem AS, Abubakar OK, Ubaka AU. Application of gold nanoparticles for improved drug efficiency. ADV NAT SCI-NANOSCI. 2017; 8(3): 14-35.
21.Kumar D, Meenan BJ, Dixon D. Glutathione-mediated release of Bodipy from PEG cofunctionalizationed gold nanoparticles. Int J Nanomedicine. 2012; 7: 4007.
22.Kumar D, Meenan BJ, Mutreja I, D’SA AR, Dixon D. Controlling the size and size distribution of gold nanoparticles: a design of experiment study. Int J Nanosci. 2012; 11(2): 1250023.
23.Young JK, Lewinski NA, Langsner RJ, Kennedy LC, Satyanarayan A, Nammalvar V, Lin AY, Drezek RA. Drezek1Size-controlled synthesis of monodispersed gold nanoparticles via carbon monoxide gas reduction. Nanoscale Res Lett. 2011; (16)6: 428.
24.Haiss W, Thanh NT, Aveyard J, Fernig DG. Determination of Size and Concentration of Gold Nanoparticles from UV−Vis Spectra. Anal Chem. 2007; 79 (11): 4215–4221.
25.Khan AK, Rashid R, Murtaza G, Zahra A. Gold nanoparticles: synthesis and applications in drug delivery. TROP J PHARM RES. 2014; 13(7): 1169-1177.
26.Malarkodi C, Rajeshkumar S, Vanaja M, Paulkumar K, Gnanajobitha G, Annadurai G. Eco-friendly synthesis and characterization of gold nanoparticles using Klebsiella pneumoniae. J Nanostructure Chem. 2013; 3(1): 30.