Leishmaniasis and Chagas disease: Is there hope in nanotechnology to fight neglected tropical diseases?

Abstract

Nanotechnology is revolutionizing many sectors of science, from food preservation to healthcare to energy applications. Since 1995, when the first nanomedicines started being commercialized, drug developers have relied on nanotechnology to improve the pharmacokinetic properties of bioactive molecules. The development of advanced nanomaterials has greatly enhanced drug discovery through improved pharmacotherapeutic effects and reduction of toxicity and side effects. Therefore, highly toxic treatments such as cancer chemotherapy, have benefited from nanotechnology. Considering the toxicity of the few therapeutic options to treat neglected tropical diseases, such as leishmaniasis and Chagas disease, nanotechnology has also been explored as a potential innovation to treat these diseases. However, despite the significant research progress over the years, the benefits of nanotechnology for both diseases are still limited to preliminary animal studies, raising the question about the clinical utility of nanomedicines in this field. From this perspective, this review aims to discuss recent nanotechnological developments, the advantages of nanoformulations over current leishmanicidal and trypanocidal drugs, limitations of nano-based drugs, and research gaps that still must be filled to make these novel drug delivery systems a reality for leishmaniasis and Chagas disease treatment.

In vitro anti-trypanosomal activity of 3-(aryl)-6-piperazin1,2,4-triazolo[3,4-a]phthalazines-loaded ultrathin polymeric particles: effect of polymer type and particle size

“…10 That effectiveness is associated either with the improvement of the therapeutic effect and decrease of toxicity or with the improvement of pharmacokinetic parameters, which could be favored by controlled drug delivery. 5 In the current study, we used PLA, PCL and PLGA polymeric matrices to construct the microparticle/nanoparticle encapsulates of two 3-(3-aryl)-6-piperazin-1,2,4-triazolo[3,4- a ]phthalazines, seeking to improve its known leishmanicidal activity. The new encapsulate chemical systems were extended to assess their effectiveness against the T. cruzi parasite.…”

“…Thus, the partial activation of the host cell from a controlled drug delivery method is an attractive strategy for the design of antileishmanial agents, which could be extended to Chagas disease. 5…”

“…Thus, the partial activation of the host cell from a controlled drug delivery method is an attractive strategy for the design of antileishmanial agents, which could be extended to Chagas disease. 5 Based on the aspects mentioned above, either two PLA-NPs or two PCL-NPs were obtained for both TF1 and TF2 to give eight formulations: PLA-TF1-600/1200, PLA-TF1-1200/2000, PCL-TF1-600/2000, PCL-TF1-1200/2000, PLA-TF2-300/600, PLA-TF2-300/3000, PCL-TF2-600-2000 and PCL-TF2-600/3000. For PLGA, only a PLGA-NP system was obtained for each compound, TF1 and TF2.…”

“…In this sense, the development of drug delivery systems (DDSs) is an attractive alternative to design leishmanicidal or antichagasic formulation drugs. 5,6 The DDSs favor a controlled drug release post-administration, improving the bioavailability and pharmacokinetic parameters of the encapsulated drug, as well as reducing toxicity side effects. 5 These nanoformulations have overcome biological barriers, such as gastrointestinal pH or blood-brain barrier, without any loss of drug efficacy.…”

Neglected Zoonotic Diseases: Advances in the Development of Cell-Penetrating and Antimicrobial Peptides against Leishmaniosis and Chagas

“…In addition, the treatment of choice with conventional drugs, which include antimonials, miltefosine or liposomal amphotericin B (AmBisome®) against some Leishmania species (due to the difference between the clinical forms of leishmaniosis, there is no universal treatment), or benznidazole and nifurtimox against T. cruzi infection, are not completely effective at eradicating these parasitoses. Furthermore, conventional pharmacological therapies have been limited due to the toxicity and side effects [36][37][38][39]. At this point, AMPs and CPPs represent a very promising opportunity to overcome these limitations and develop new therapies [40].…”