Exploring the potential of antimalarial nanocarriers as a novel therapeutic approach

Malaria is a disease caused by a parasite that may be transmitted to humans via the bites of certain mosquitoes. It is still among the topmost public health concerns worldwide, mostly prevalent in tropical and subtropical areas. According to WHO, approximately 229 million cases were reported globally last few years, causing death for about 409,000 people [1]. Even though measures have been taken to control or eradicate malaria, its prevention and treatment methods need improvement since it impacts individuals living mainly within sub-Saharan Africa, Southeast Asia as well as Latin America regions [2].

There exist numerous medical hypotheses about the origins of malaria and optimal methodologies for its cure. The most accepted hypothesis says that a parasite named Plasmodium is responsible, necessitating antimalarial agents to be administered as treatment [3]. The primary mechanism of action for these drugs is the elimination of the target pathogen from the circulatory system and the prevention of its spreading to other organs. However, resistance to these antimalarials from the organism has forced scientists to acquire other therapeutic techniques, the investigation of which must commence immediately.

It has been hypothesized that malaria may arise from a confluence of inherited traits and various external circumstances. It is suggested to employ preventative tactics, such as insecticides or mosquito nets, to diminish the population of mosquitoes capable of transmitting this ailment [4]. Furthermore, scientists must explore different forms of immunization against this parasite; new vaccines are necessary if we hope to deter further transmissions among the populace.

Various hypotheses propose a connection between malaria and impoverished living conditions, including inadequate nourishment. There is an urgent requirement for medical investigations to advance malaria treatment, given the various existing hypotheses.

Primary ways to address malaria involve administering medications such as chloroquine, artemisinin-based combination therapies (ACTs), or quinine which act by destroying the parasites responsible for this disease [4]. Yet, these remedies have become less reliable due to their failures in killing newer strains of drug-resistant organisms that can resist them now. Furthermore, transporting drugs efficiently enough toward specific cells while sparing the patient from harmful effects remains a major hurdle against effective treatment protocols.

Conventional malaria treatments include the use of antibiotics and antimalarial drugs. Medicines, including chloroquine, ACTs, and quinine, have been employed due to their ability to eliminate the parasite causing malaria within a human's body [4]. However, these drugs' effectiveness has lately come under question because of specific strains becoming drug-resistant, which is concerning as it hinders efforts at treating infected individuals completely without any hovering risks or complications that can arise from our current solutions, like toxins passed on during administration, etc.

Lately, there has been a growing unease over the emergence of drug tolerance in Plasmodium parasites. This issue could result in treatment inadequacy and an expansion of this ailment to more individuals. Multiple genetic changes have surfaced within target protein encodings for antimalarial treatments like chloroquine, sulfadoxine-pyrimethamine, ACTs creating additional concern [5].

The pfcrt gene is famous for the K76T mutation, which has been linked to chloroquine resistance [6]. The occurrence of this mutation in regions where once effective drugs like chloroquine were predominantly led to its removal as a front-line treatment option.

There is yet another genetic variation that has caused worry, named N86Y. This mutation appears in a gene called P. falciparum multidrug resistance 1 (pfmdr1) and brings with it concerns about its association with both chloroquine as well as ACTs resistance [7]. Many places where these same therapies are used have also detected this very mutation, leaving some wondering if their efficacy might be questioned going forward into the future.

Apart from the aforementioned mutations, worries have arisen about artemisinin resistance. At present, these drugs are considered to be the most efficacious antimalarial treatment options available. Several investigations have detected changes in the P. falciparumkelch 13 (pfk13) gene, which correspond with developing an immunity towards artemisinins [8]. These genetic alterations can be found throughout various parts of Southeast Asia, where there has been extensive use of this therapy. Experts fear that without proper intervention, they may spread elsewhere too.

The effects of mutations on the advancement of malaria treatments carry weighty significance. The rise in drug-resistant parasites poses impediments to disease regulation and necessitates novel therapeutic approaches that can surmount these complications. Scientists are actively involved in devising fresh medicines geared towards diverse branches within the parasite's progression cycle while pinpointing newer targets less prone to developing resistance. Furthermore, there are ongoing attempts to create fresh drug delivery ideas for observing drug resilience and enhancing the efficiency of current medications by utilizing a combination of therapies along with other approaches.

The utilization of nanotechnology offers a promising method for the creation of improved and focused treatments for malaria. One noteworthy benefit that arises from employing nanotechnology is its ability to design small carriers which can encase drugs while transporting them to designated cells or tissues [9]. These transporters, called nanocarriers (NCs), are generally made up of materials such as lipids, polymers, or metals that align with biological compatibility standards and eventually attain abilities through functionalization, thus offering more control over the delivery process by targeting distinct cell types or tissues specifically [10,11].

The incorporation of NCs could intensify the efficiency of antimalarial medications by elevating their pharmacokinetics and pharmacodynamics. Imprisoning these drugs into NCs might result in greater levels of the drug-targeted cells or tissues, lowering systemic exposure and decreasing adverse consequences [10]. Furthermore, NCs possess a defensive capacity against drug deterioration as well as an escalation in their stability which facilitates improved medication delivery for more favorable results. Apart from just delivering drugs, there are further uses for NCs that involve creating new prevention methods. One potential use is to modify the NC with antigens to enhance the body's immune response against malaria parasites. By doing so, it may be possible to circumvent challenges faced by traditional vaccine development, such as needing many doses and generating a robust enough immunity reaction [12].

Numerous NCs have been explored as potential malaria treatments, each with distinct characteristics. A major obstacle in creating NC-based remedies for malaria is the necessity to establish biocompatibility and minimal toxicity of these compounds [10]. This concern intensifies when designing treatments that will be given to susceptible groups, including pregnant women or small children. Additionally, scientists are striving to refine the pharmacokinetic and pharmacodynamic profiles of NC-based medications to guarantee their efficacy while minimizing any risks associated with them.

All in all, the field of nanotechnology possesses a great amount of promise when it comes to altering and improving how we treat malaria. With the creation of NCs capable of enclosing drugs for targeted delivery purposes, there is room for progress toward furthering antimalarial drug efficacy while minimizing any negative secondary effects [12]. Additionally, these same NCs may be utilized as a medium wherein new prevention measures can come into existence, such as antigen-focused vaccines. More investigations must occur before full optimization takes place on this front, however. This article aims to present an overview of the malaria parasite life cycle, its pathophysiology, current treatment options, and the therapy gap that currently exists. It delves into the many nanocarriers used to improve the efficacy of antimalarial medications, including liposomes, ethosomal cataplasm, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanocarriers, and metallic nanoparticles [10]. NCs are a viable therapeutic method for treating malaria due to their better pharmacokinetics, higher drug bioavailability, and lower toxicity, all of which are highlighted in the current work.

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