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Novel Pharmaceuticals Development and Delivery Systems for the Treatment of...
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Novel Pharmaceuticals Development and Delivery Systems for the Treatment of Parasitic Diseases, 2nd Edition

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 5140

Special Issue Editor

Dr. Maria João Gouveia

E-Mail Website
Guest Editor
1. Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), Centre for the Study in Animal Science (CECA), University of Porto, Praça do Coronel Pacheco 42, 4050-083 Porto, Portugal
2. Centre for Parasite Biology and Immunology, Department of Infectious Diseases, National Health Institute Dr. Ricardo Jorge, Rua Alexandre Herculano 321, 4000-055 Porto, Portugal
Interests: carcinogenesis; helminth-associated carcinogenesis; combine therapy; immunotherapy; protein recombinant; parasites; schistosoma; opisthorchis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Parasitic infections such as malaria, schistosomiasis, and leishmaniasis, among others, remain a major public health problem causing substantial mortality and morbidity worldwide. Antiparasitic drugs are available, but they are not ideal and present major disadvantages. Furthermore, there is a real concern regarding the development of drug resistance (e.g., primaquine for malaria). Few novel antiparasitic drugs have emerged in recent decades, and the discovery and development of novel antiparasitic drugs are urgently needed. Strategies such as combinations of existing drugs, improvements to known drugs, de novo discovery, and/or the exploration of natural bioactive compounds, among others, should be explored to improve the treatment of parasitic infections and prevent the development of drug resistance.

This Special Issue aims to discuss strategies for the discovery and development of novel treatments for parasitic diseases, as well as advanced drug delivery technology. The design and synthesis of novel drugs or drug derivatives and their antiparasitic activities, structure–activity relationships (SARs), the use of bioinformatics tools (or others) for the discovery of potential drugs, and natural compounds as sources of antiparasitic drugs will be addressed here. Colleagues are invited to submit original research papers, communications, or review articles to this Special Issue.

Dr. Maria João Castro Gouveia
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

  • parasites
  • drug synthesis and discovery
  • natural bioactive compounds
  • drug combinations
  • parasitic diseases
  • neglected tropical diseases
  • novel therapeutic strategies
  • optimization
  • formulations
  • mechanism of action
  • screening assays
  • pharmacodynamics
  • pharmacokinetics
  • drug resistance
  • antiparasitic activity

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Related Special Issue

Published Papers (4 papers)

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Research

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17 pages, 2738 KiB  
Article
Deciphering Chemical Rules for Drug Penetration into Strongyloides
by Miguel Marín, Javier Sánchez-Montejo, Sergio Ramos, Antonio Muro, Julio López-Abán and Rafael Peláez
Pharmaceutics 2024, 16(9), 1224; https://doi.org/10.3390/pharmaceutics16091224 - 19 Sep 2024
Viewed by 707
Abstract
Background: Strongyloidiasis, a parasitic infection, presents a significant public health challenge in tropical regions due to the limited repertoire of effective treatments. The screening of chemical libraries against the therapeutically relevant third-stage larvae (L3) of the model parasite Strongyloides venezuelensis yielded meager success [...] Read more.
Background: Strongyloidiasis, a parasitic infection, presents a significant public health challenge in tropical regions due to the limited repertoire of effective treatments. The screening of chemical libraries against the therapeutically relevant third-stage larvae (L3) of the model parasite Strongyloides venezuelensis yielded meager success rates. This situation is reminiscent of Gram-negative bacteria, where drug entry is a limiting factor. Methods: Here, we set out to determine whether similar barriers are in place and establish whether structural and property requirements exist for anti-strongyloides drug discovery. We focused on dyes as their uptake and effects on viability can be independently assessed in the multicellular parasite, thus providing a means to study the possibility of similar entry rules. We tested different dyes in in vitro assays on L3s. Results: We found that staining was necessary to reduce parasite viability, with some dyes achieving anti-strongyloides effects at concentrations similar to those of the reference drug, ivermectin (IV). Some dyes also showed activity against female adults at concentrations well below that of ivermectin. Unfortunately, the most potent dye, Methylene Blue, was unable to prevent the infection in a preliminary in vivo mouse model assay, presumably due to fast dye clearance. Structural analysis showed that positive charges facilitated the access of the compounds to the L3 tissue, thus providing a structural tool for the introduction of activity. For female adults, low globularity is additionally required. As a proof of concept, we added a positive charge to an inactive compound of one of our chemical libraries and re-determined the activity. Conclusions: These findings allow us to establish structural rules for parasite entry that could be of interest for future drug screening or drug development campaigns. These rules might also be applicable to other related parasites. Full article
(This article belongs to the Special Issue Novel Pharmaceuticals Development and Delivery Systems for the Treatment of Parasitic Diseases, 2nd Edition)
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19 pages, 7004 KiB  
Article
Green Synthesis of Chitosan/Silver Nanoparticles Using Citrus paradisi Extract and Its Potential Anti-Cryptosporidiosis Effect
by Muslimah N. Alsulami and Eman S. El-Wakil
Pharmaceutics 2024, 16(7), 968; https://doi.org/10.3390/pharmaceutics16070968 - 22 Jul 2024
Viewed by 919
Abstract
Cryptosporidium parvum (C. parvum) is one of the most prevalent species infecting humans and animals. Currently, the only FDA-licensed drug to treat cryptosporidiosis is nitazoxanide (NTZ), with no efficacy in immunocompromised hosts. Citrus paradisi (C. paradisi) has demonstrated anti-protozoal [...] Read more.
Cryptosporidium parvum (C. parvum) is one of the most prevalent species infecting humans and animals. Currently, the only FDA-licensed drug to treat cryptosporidiosis is nitazoxanide (NTZ), with no efficacy in immunocompromised hosts. Citrus paradisi (C. paradisi) has demonstrated anti-protozoal activities. This study aimed to investigate the anti-cryptosporidiosis effect of C. paradisi peel extract, either alone or in mediating the green synthesis of chitosan silver nanoparticles (Cs/Ag NPs), compared to NTZ. Mice were sorted into nine different groups. The effectiveness of the treatments was evaluated using parasitology, histopathology, immunohistochemistry, and immunology. C. paradisi outperformed nitazoxanide regarding oocyst shedding (79% vs. 61%). The effectiveness of NTZ Cs/Ag NPs and Citrus Cs/Ag NPs was enhanced to 78% and 91%, respectively. The highest oocyst inhibition was obtained by combining NTZ and Citrus Cs/Ag NPs (96%). NF-κB, TNF-α, and Il-10 levels increased in response to infection and decreased in response to various treatments, with the highest reduction in the group treated with combined NTZ citrus Cs/Ag NPs. Combining C. paradisi with NTZ could have a synergistic effect, making it a potentially effective anti-cryptosporidiosis agent. Utilizing C. paradisi in the green synthesis of Cs/Ag NPs improves the therapeutic response and can be used to produce novel therapeutic antiparasitic drugs. Full article
(This article belongs to the Special Issue Novel Pharmaceuticals Development and Delivery Systems for the Treatment of Parasitic Diseases, 2nd Edition)
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15 pages, 4443 KiB  
Article
A Surprising Repurposing of Central Nervous System Drugs against Squamous Cell Carcinoma of the Bladder, UM-UC-5
by Maria João Gouveia, Eduarda Ribeiro and Nuno Vale
Pharmaceutics 2024, 16(2), 212; https://doi.org/10.3390/pharmaceutics16020212 - 31 Jan 2024
Cited by 1 | Viewed by 1586
Abstract
The potential benefits of drug repurposing have gained attention as an alternative to developing de novo drugs. The potential of using central nervous system (CNS) drugs as anticancer drugs has been explored in several types of human cancers, such as breast and colon [...] Read more.
The potential benefits of drug repurposing have gained attention as an alternative to developing de novo drugs. The potential of using central nervous system (CNS) drugs as anticancer drugs has been explored in several types of human cancers, such as breast and colon cancer, among others. Here, we examine the effect of the CNS drugs sertraline, paroxetine, and chlorpromazine on human squamous carcinoma cells of the bladder (UM-UC-5). After exposing UM-UC-5 cells to increased concentrations of each drug for 48 h, we assessed their metabolic activity using an MTT assay. Based on those results, we calculated cell viability and the half-maximal inhibitory concentration (IC50) values. The results suggest that the CNS drugs were effective against UM-UC-5 in the order of potency of sertraline > chlorpromazine > paroxetine. Interestingly, sertraline was more potent than 5-fluorouracil (5-FU), a widely used anticancer drug. This study demonstrated, for the first time, the promising anticancer activity of CNS drugs on human bladder cancer cells in vitro and supports the repurposing of CNS drugs to improve cancer treatment. Nevertheless, further studies are necessary to understand their mechanism of action and in vivo activity. Full article
(This article belongs to the Special Issue Novel Pharmaceuticals Development and Delivery Systems for the Treatment of Parasitic Diseases, 2nd Edition)
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Review

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33 pages, 1636 KiB  
Review
Combination Therapy and Phytochemical-Loaded Nanosytems for the Treatment of Neglected Tropical Diseases
by Jacqueline Soto-Sánchez and Gilberto Garza-Treviño
Pharmaceutics 2024, 16(10), 1239; https://doi.org/10.3390/pharmaceutics16101239 - 24 Sep 2024
Viewed by 916
Abstract
Background: Neglected tropical diseases (NTDs), including leishmaniasis, trypanosomiasis, and schistosomiasis, impose a significant public health burden, especially in developing countries. Despite control efforts, treatment remains challenging due to drug resistance and lack of effective therapies. Objective: This study aimed to synthesize the [...] Read more.
Background: Neglected tropical diseases (NTDs), including leishmaniasis, trypanosomiasis, and schistosomiasis, impose a significant public health burden, especially in developing countries. Despite control efforts, treatment remains challenging due to drug resistance and lack of effective therapies. Objective: This study aimed to synthesize the current research on the combination therapy and phytochemical-loaded nanosystems, which have emerged as promising strategies to enhance treatment efficacy and safety. Methods/Results: In the present review, we conducted a systematic search of the literature and identified several phytochemicals that have been employed in this way, with the notable efficacy of reducing the parasite load in the liver and spleen in cases of visceral leishmaniasis, as well as lesion size in cutaneous leishmaniasis. Furthermore, they have a synergistic effect against Trypanosoma brucei rhodesiense rhodesain; reduce inflammation, parasitic load in the myocardium, cardiac hypertrophy, and IL-15 production in Chagas disease; and affect both mature and immature stages of Schistosoma mansoni, resulting in improved outcomes compared to the administration of phytochemicals alone or with conventional drugs. Moreover, the majority of the combinations studied demonstrated enhanced solubility, efficacy, and selectivity, as well as increased immune response and reduced cytotoxicity. Conclusions: These formulations appear to offer significant therapeutic benefits, although further research is required to validate their clinical efficacy in humans and their potential to improve treatment outcomes in affected populations. Full article
(This article belongs to the Special Issue Novel Pharmaceuticals Development and Delivery Systems for the Treatment of Parasitic Diseases, 2nd Edition)
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