Selective Antiprotozoal Activity of Nitric Oxide-releasing Chitosan Nanoparticles Against Trypanosoma cruzi: Toxicity and Mechanisms of Action

Lancheros, César Armando Contreras; Pelegrino, Milena T.; Kian, Danielle; Tavares, Eliandro Reis; Hiraiwa, Priscila Mazzocchi; Goldenberg, Samuel; Nakamura, Celso Vataru; Yamauchi, Lucy Megumi; Pinge‐Filho, Phileno; Seabra, Amedea B.; Yamada‐Ogatta, Sueli Fumie

doi:10.2174/1381612824666180209105625

Cited by 19 publications

(40 citation statements)

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“…Biocompatibility, biodegradability and safety of the polymer are essential features to consider when designing PNs. In this sense, the natural polymer CS and its derivatives deserve to be commented as relevant platforms for nanotherapeutic applications, including antimicrobial therapies [ 75 , 76 , 77 ]. CS is classified by the FDA as “generally regarded as safe.” It has been extensively studied in nanotherapeutics and nowadays, there are marketed CS-based formulations in nutraceutical and medical devices [ 44 , 78 ].…”

Section: Polymeric Nanocarriers Against Intracellular Infections: mentioning

confidence: 99%

Recent Advances in Polymeric Nanoparticle-Encapsulated Drugs against Intracellular Infections

2020

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Polymeric nanocarriers (PNs) have demonstrated to be a promising alternative to treat intracellular infections. They have outstanding performance in delivering antimicrobials intracellularly to reach an adequate dose level and improve their therapeutic efficacy. PNs offer opportunities for preventing unwanted drug interactions and degradation before reaching the target cell of tissue and thus decreasing the development of resistance in microorganisms. The use of PNs has the potential to reduce the dose and adverse side effects, providing better efficiency and effectiveness of therapeutic regimens, especially in drugs having high toxicity, low solubility in the physiological environment and low bioavailability. This review provides an overview of nanoparticles made of different polymeric precursors and the main methodologies to nanofabricate platforms of tuned physicochemical and morphological properties and surface chemistry for controlled release of antimicrobials in the target. It highlights the versatility of these nanosystems and their challenges and opportunities to deliver antimicrobial drugs to treat intracellular infections and mentions nanotoxicology aspects and future outlooks.

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Section: Polymeric Nanocarriers Against Intracellular Infections: mentioning

confidence: 99%

Recent Advances in Polymeric Nanoparticle-Encapsulated Drugs against Intracellular Infections

2020

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“…Since then, the enthusiasm for researches on NO has almost reached the peak, and it has been increasingly valued in biology and medicine. To sum up, the roles played by endogenous NO in the human body are as follows: (i) NO is an endothelium-derived relaxing factor that relaxes vascular smooth muscle and prevents platelet aggregation [22,23]; (ii) NO is a reverse messenger of nerve conduction and plays an important role in the process of learning and memorization [24,25]; (iii) when activated upon phagocytosis and stimulation, macrophages release NO as toxic molecules that kill foreign invading microorganisms and tumor cells [26,27,28,29]; (iv) as a free radical, NO can damage normal cells, which plays an important role in myocardial and brain ischemia–reperfusion injuries [30,31]; and (v) NO can regulate the inflammatory reaction and cell proliferation processes, which are key to the wound healing process [32,33,34].…”

Section: Introductionmentioning

confidence: 99%

Nitric Oxide-Releasing Polymeric Materials for Antimicrobial Applications: A Review

et al. 2019

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Polymeric materials releasing nitric oxide have attracted significant attention for therapeutic use in recent years. As one of the gaseous signaling agents in eukaryotic cells, endogenously generated nitric oxide (NO) is also capable of regulating the behavior of bacteria as well as biofilm formation in many metabolic pathways. To overcome the drawbacks caused by the radical nature of NO, synthetic or natural polymers bearing NO releasing moiety have been prepared as nano-sized materials, coatings, and hydrogels. To successfully design these materials, the amount of NO released within a certain duration, the targeted pathogens and the trigger mechanisms upon external stimulation with light, temperature, and chemicals should be taken into consideration. Meanwhile, NO donors like S-nitrosothiols (RSNOs) and N-diazeniumdiolates (NONOates) have been widely utilized for developing antimicrobial polymeric agents through polymer-NO donor conjugation or physical encapsulation. In addition, antimicrobial materials with visible light responsive NO donor are also reported as strong and physiological friendly tools for rapid bacterial clearance. This review highlights approaches to delivery NO from different types of polymeric materials for combating diseases caused by pathogenic bacteria, which hopefully can inspire researchers facing common challenges in the coming ‘post-antibiotic’ era.

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“…For example, nitric oxide acts as an endogenous signaling molecule influencing host immune responses to protozoan parasites in a positive manner and promoting subsequent reduction of parasitic burden. It has been shown that systemically administered nanoparticles possess the capability to release nitric oxide at targeted sites within the body or intracellularly within macrophages [102, 105]. Given the beneficial effect of nitric oxide on protozoan disease progression, nitric oxide releasing functionalized nanoparticles present possible alternatives to traditional toxic front-line chemotherapeutic options.…”

Section: Resultsmentioning

confidence: 99%

“…Treatment of peritoneal macrophages with these nanoparticles decreased the number of T. cruzi infected cells and the average number of intracellular replicative amastigotes per infected cell. These results suggest that the S-nitroso-MSA-CS NPs are promising nanocarriers for the treatment of Chagas disease and can deliver nitric oxide intracellularly [102]. Ursolic acid loaded poly-ε-caprolactone nanoparticles have also been evaluated in vivo showing similar efficacy to BZN standard formulations [103].…”

Section: Nanospheresmentioning

confidence: 99%

Nanoparticulate drug delivery systems for the treatment of neglected tropical protozoan diseases

Volpedo

Costa

Ryan

et al. 2019

J. Venom. Anim. Toxins incl. Trop. Dis

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Neglected Tropical Diseases (NTDs) comprise of a group of seventeen infectious conditions endemic in many developing countries. Among these diseases are three of protozoan origin, namely leishmaniasis, Chagas disease, and African trypanosomiasis, caused by the parasites Leishmania spp. , Trypanosoma cruzi , and Trypanosoma brucei respectively. These diseases have their own unique challenges which are associated with the development of effective prevention and treatment methods. Collectively, these parasitic diseases cause more deaths worldwide than all other NTDs combined. Moreover, many current therapies for these diseases are limited in their efficacy, possessing harmful or potentially fatal side effects at therapeutic doses. It is therefore imperative that new treatment strategies for these parasitic diseases are developed. Nanoparticulate drug delivery systems have emerged as a promising area of research in the therapy and prevention of NTDs. These delivery systems provide novel mechanisms for targeted drug delivery within the host, maximizing therapeutic effects while minimizing systemic side effects. Currently approved drugs may also be repackaged using these delivery systems, allowing for their potential use in NTDs of protozoan origin. Current research on these novel delivery systems has provided insight into possible indications, with evidence demonstrating their improved ability to specifically target pathogens, penetrate barriers within the host, and reduce toxicity with lower dose regimens. In this review, we will examine current research on these delivery systems, focusing on applications in the treatment of leishmaniasis, Chagas disease, and African trypanosomiasis. Nanoparticulate systems present a unique therapeutic alternative through the repositioning of existing medications and directed drug delivery.

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Selective Antiprotozoal Activity of Nitric Oxide-releasing Chitosan Nanoparticles Against Trypanosoma cruzi: Toxicity and Mechanisms of Action

Abstract: S-nitroso-MSA-CS NPs are promising nanocarriers for the treatment of Chagas's disease.

Cited by 19 publications

References 0 publications

Recent Advances in Polymeric Nanoparticle-Encapsulated Drugs against Intracellular Infections

Recent Advances in Polymeric Nanoparticle-Encapsulated Drugs against Intracellular Infections

Nitric Oxide-Releasing Polymeric Materials for Antimicrobial Applications: A Review

Nanoparticulate drug delivery systems for the treatment of neglected tropical protozoan diseases

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