ReviewRecent advances in use of silver nanoparticles as antimalarial agents
Graphical abstract
Malaria is one of the most common infectious diseases, which has become a great public health problem all over the world. In effectiveness of available antimalarial treatment and emergence of drug resistance is the main reason behind its menace. In this context, nanotechnology will be the only solution for the control of malaria.
Introduction
In the year 2000, estimated malaria incidence was approximately 262 million cases worldwide, of which approximately 839,000 resulted in death. However, in 2015, these figures declined, with approximately 214 million cases worldwide and 438,000 deaths (WHO, 2015). Although, the number of cases of the diseases was reduced, malaria is still a highly prevalent disease in tropical and sub-tropical countries. It is caused by protozoan parasites belonging to the Plasmodium genus. Among hundreds of species, four are of great importance for disease manifestation in humans viz. Plasmodium malariae, P. ovale, P. vivax and P. falciparum – all transmitted through female Anopheles mosquito bite (Aditya et al., 2013). A single mosquito bite introduces various Plasmodium species into the host; and of these different species, P. falciparum is the most dangerous and prevalent in Africa and India, accounting for the majority of malaria-related deaths. P. vivax has a wider geographical distribution than P. falciparum because this species can grow in Anopheles mosquito at lower temperatures and can survive at higher altitudes (WHO, 2015).
Malaria is among the world's neglected diseases, which do not only persist in conditions of poverty but also contribute to the maintenance of socio-economical inequality. The affected population has little financial support; therefore, the medical and pharmaceutical industry has no interest in the development of new drugs and treatments, which would result in a limited monetary return. Disease control measures are yet challenging and include: (i) vector control by insecticide utilization; (ii) chemoprevention by compounds that prevent the blood stage infection, and (iii) diagnosis and treatment (WHO, 2015). Treatment regimens often include ≥2 associated drugs that cause side effects and have poor patient adherence. The absence of an effective vaccine and mechanisms of resistance to traditionally used drugs and insecticides render it even more critical to control the disease and execute measures for its elimination (Santos-Magalhaes and Mosqueira, 2010).
Due to unavailability of effective treatment strategies, transmission vector elimination is an important tool to control the vector borne diseases. Use of insecticides in malaria endemic areas is essential for protection against the disease because the vector transmission rate is extremely high (Murugan et al., 2015). However, the toxicity of insecticides to humans and the environment has generated pressing need to search for novel antimalarial compounds. In this context, nanotechnology-based products (nanomaterials) would be helpful in the management of malaria. The nanomaterials have a wide range of applications particularly in medicine, which contributes to major advances in the development of materials for increasing drug efficacy, drug delivery, reducing toxicity of compounds and enabling scheduled and sustained release of nanomaterials.
Section snippets
Malaria – a major threat
The incidence of pathogens associated with vectors, such as mosquitoes and other insects, are common issues in tropical and sub-tropical countries (Veerakumar and Govindarajan, 2014). Because of typical climatic conditions, such as rising temperature in the most affected areas, and social causes (uncontrolled and disorganized occupation of locations close to forests and mosquitoes breeding sites), malaria is yet a serious health issue. Parasite life cycle is substantially the same in the four
Life cycle of malaria
As previously mentioned, malaria is caused by the transmission of a parasite (Plasmodium) by female Anopheles mosquito. The malarial infection begins with injection of Plasmodium sp. into human body by mosquitoes at the time of blood meal. After infection, the parasite is carried by the circulatory system to the liver and erythrocytes (red blood cells), where it undergoes asexual replication and forms gametocytes. The life cycle of malaria requires two hosts for its completion (Fig. 1). The
Existing antimalarial drugs
Antimalarial drugs available to date are mainly used for the prevention and treatment of malarial infection. Most of the antimalarial drugs target the erythrocytic stage of the infection, which is considered as the phase that causes symptomatic illness. However, the hepatic stage (preerythrocytic stage) activity for most antimalarial drugs is not well studied (http://www.uptodate.com/contents/antimalarial-drugs-an-overview). Various programs like the malaria eradication campaign and others,
Resistance to antimalarial drugs
Although, various antimalarial drugs discussed above have been employed for their significant efficacy against malarial parasites, the widespread overuse of antimalarial drugs resulted in the development of resistance to almost all the pharmaceuticals discovered to date. In addition, the conditions in which the drugs are used act as one of the most important factors responsible for the development of resistance (White, 2004). It was reported that some antimalarial drugs are effective in many
Strategic role of nanotechnology in malaria
In spite of its diffusion, malaria is a preventable and curable disease (Bruxvoort et al., 2014), with a well-established treatment regimen that often includes the use of some effective antimalarial drugs alone or in combinations, defined according to the type of disease manifestation, presence or absence of Plasmodium resistance and the type of infecting species. Despite treatment availability, patient adhesion is critical for its success and to prevent disease recurrence and consequently,
Nanocarriers for targeted drug delivery in malaria
The main goal of using nanocarriers for drug delivery in malaria treatment is to overcome problems faced by conventional therapies. The problem of emerging resistance to antimalarial drugs is the main drawback of conventional therapy for malaria treatment. Certain features like low bioavailability, rapid metabolism and poor absorption make antimicrobial drug less effective (Anand et al., 2007, Miotto et al., 2013). However, the unique and special features of nanoparticles such as small size,
Toxicological issues
Although, AgNPs show antimalarial effects, the assessment of the risk associated with their use is also an essential factor (Krug, 2014). During recent era, the harmful effects of AgNPs are getting a wide attention for various applications and socio-economic benefits (Asmonaite et al., 2016). Many reports have claimed the toxicity of AgNPs to humans, animals and environment (Asharani et al., 2009, Gupta et al., 2015). In this context, the nanotoxicity studies have been directed towards the
Conclusions
Malaria is responsible for high morbidity and mortality throughout the world particularly in tropical and subtropical zones. Since its discovery many strategies have been employed for its control. The controlling mechanisms were mainly focused on inhibition of malarial parasite and vectors. Due to easy availability and curative properties, plants and their alkaloids have been used since the time immemorial for treatment of malaria. Synthetic insecticides such as DDT were used for the control of
Conflict of interest
The authors do not have conflict of interest to declare.
References (154)
- et al.
Synthesis and applications of silver nanoparticles
Arab. J. Chem.
(2010) - et al.
Advances in nanomedicines for malaria treatment
Adv. Colloid Interface Sci.
(2013) - et al.
Behavioural toxicity assessment of silver ions and nanoparticles on zebrafish using a locomotion profiling approach
Aquat. Toxicol.
(2016) - et al.
Glycodendrimeric nanoparticulate carriers of primaquine phosphate for liver targeting
Int. J. Pharm.
(2005) - et al.
Interactions with heparin-like molecules during erythrocyte invasion by Plasmodium falciparum merozoites
Blood
(2010) - et al.
Quinoline antimalarials: mechanisms of action and resistance and prospects for new agents
Pharmacol. Ther.
(1998) - et al.
Site of action of the antimalarial hydroxynaphthoquinone, 2-[trans-4-(40-chlorophenyl) cyclohexyl]-3-hydroxy-1,4-naphthoquinone (566 C80)
Biochem. Pharmacol.
(1992) - et al.
Current perspectives on the mechanism of action of artemisinins
Int. J. Parasitol.
(2006) - et al.
Clerodendrum chinense-mediated biofabrication of silver nanoparticles: mosquitocidal potential and acute toxicity against non-target aquatic organisms
J. Asia. Pac. Entomol.
(2016) - et al.
Green synthesis and characterization of silver nanoparticles fabricated using Anisomeles indica: mosquitocidal potential against malaria, dengue and Japanese encephalitis vectors
Exp. Parasitol.
(2016)
Toxicity of fungal-generated silver nanoparticles to soil-inhabiting Pseudomonas putida KT2440, a rhizospheric bacterium responsible for plant protection and bioremediation
J. Hazard. Mater.
Synthesis, structures, and antimalarial activities of some silver(I), gold(I) and gold(III) complexes involving N-heterocyclic carbene ligands
Eur. J. Med. Chem.
The principles and applications of avidin-based nanoparticles in drug delivery and diagnosis
J. Control. Release
Audiometry as a possible indicator of quinine plasma concentration during treatment of malaria
Trans. R. Soc. Trop. Med. Hyg.
Cardiac dysfunction in cirrhosis
Best Pract. Res. Clin. Gastroenterol.
Cardiotoxicity reduction induced by halofantrine entrapped in nanocapsule devices
Life Sci.
Severe allergic reactions to oral artesunate: a report of two cases
Trans. R. Soc. Trop. Med. Hyg.
Quinine and severe falciparum malaria in late pregnancy
Lancet
Noble metals in medicine: latest advances
Coord. Chem. Rev.
The algal toxicity of silver engineered nanoparticles and detoxification by exopolymeric substances
Environ. Pollut.
Evaluation of antiplasmodial activity of green synthesized silver nanoparticles
Colloids Surf. B: Biointerfaces
Amphiphilic dendritic derivatives as nanocarriers for the targeted delivery of antimalarial drugs
Biomaterials
Antifungal activity of silver nanoparticles against Candida spp
Biomater.
Drug resistance in malaria
Ind. J. Med. Microbiol.
The effect of particle size on the cytotoxicity, inflammation, developmental toxicity and genotoxicity of silver nanoparticles
Biomaterials
Bacterial resistance to silver in wound care
J. Hosp. Infect.
Drug-resistant malaria: molecular mechanisms and implications for public health
FEBS Lett.
Amodiaquine-associated adverse effects after inadvertent overdose and after a standard therapeutic dose
Ghana Med. J.
Short peptide based nanotubes capable of effective curcumin delivery for treating drug resistant malaria
J. Nanobiotechnol.
Bioavailability of curcumin: problems and promises
Mol. Pharm.
Biosynthesized silver nanoparticles using floral extract of Chrysanthemum indicum L.-potential for malaria vector control
Environ. Sci. Pollut. Res.
Meyler's Side Effects of Antimicrobial Drugs
A Brief History of Malaria
Anti-proliferative activity of silver nanoparticles
BMC Cell Biol.
Comparison of the toxicity of silver, gold and platinum nanoparticles in developing zebra fish embryos
Nanotoxicology
Primaquine: the risks and the benefits
Malaria J.
Chloroquine resistance in Plasmodium vivax
Antimicrob. Agents Chemother.
Target nanoparticles: an appealing drug delivery platform
J. Nanomed. Nanotechnol.
In vitro antimalarial activity of metalloporphyrins against Plasmodium falciparum
Parasitol. Res.
PEGylated peptide dendrimeric carriers for the delivery of antimalarial drug chloroquine phosphate
Pharm. Res.
Asymptomatic malaria infections: detectability, transmissibility and public health relevance
Nat. Rev Microbiol.
Side effects of chloroquine and primaquine and symptom reduction in malaria endemic area (Mâncio Lima, Acre, Brazil)
Interdiscip. Perspect. Infect. Dis.
How patients take malaria treatment: a systematic review of the literature on adherence to antimalarial drugs
PLOS ONE
The development of pyrimethamine resistance by Plasmodium falciparum
Bull. World Health Organ.
Artemether-lumefantrine combination therapy for treatment of uncomplicated malaria: the potential for complex interactions with antiretroviral drugs in HIV-infected individuals
Malaria Res. Treat.
Unique cellular interaction of silver nanoparticles: size-dependent generation of reactive oxygen species
J. Phys. Chem. B
Disruption of Plasmodium falciparum erythrocyte rosettes by standard heparin and heparin devoid of anticoagulant activity
Am. J. Trop. Med. Hyg.
Renal clearance of quantum dots
Nat. Biotechnol.
A lesson learnt: the rise and fall of Lariam and Halfan
J. R. Soc. Med.
Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement?
BMC Public Health
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