Many previous studies presented the effectiveness of ketoconazole (KTZ) against leishmaniasis. However, the bioavailability and therapeutic efficacy of free KTZ are limited due to its low aqueous solubility. In this study, an inclusion complex (IC6HKTZ) was prepared with p-sulfonic acid calix[6]arene (CX6SOH) to improve the solubility and efficacy of KTZ against Leishmania amazonensis and Leishmania infantum promastigotes. A linear increase in KTZ solubility as a function of CX6SOH concentration was verified using the phase-solubility diagram. The resulting diagram was classified as A-type and a 1:1 host-guest stoichiometry was assumed to prepare IC6HKTZ by freeze-drying. FTIR, TG/DSC, XRD, and solid-state C NMR spectroscopy analyses were performed to confirm the formation of IC6HKTZ. The solubility enhancement of KTZ by 120.00 μM CX6SOH was about 95 times. The IC values of IC6HKTZ and free KTZ were 3.95 and 14.35 μM for Leishmania amazonensis and 6.74 and 17.47 μM for Leishmania infantum, respectively. The viability of DH82 macrophages was not affected by CX6SOH. These results show that CX6SOH is a new supramolecular carrier system that improves antileishmanial activities to KTZ for the treatment of cutaneous and visceral leishmaniasis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ijpharm.2023.122663 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The Potential Role of Sanguinarine as an Inhibitor of Leishmania PP2C in the Induction of Apoptosis.
Acta Parasitol
January 2025
División de Investigación, Facultad de Medicina, Unidad de Investigación UNAM-INC, Universidad Nacional Autónoma de México, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Ciudad de México, C.P. 14080, México.
Leishmania spp. cause a wide range of human diseases, localized skin lesions, mucocutaneous and visceral infections. In the present study, the aim was to investigate the potential role of sanguinarine as a specific inhibitor of Leishmania PP2C that can induce apoptosis in the parasite.
View Article and Find Full Text PDFDehydrothyrsiferol Against Cutaneous Leishmaniasis: Treatment Outcome in a Murine Model.
Mar Drugs
December 2024
Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La Laguna (ULL), Avenida Astrofísico Francisco Sánchez s/n, 38206 La Laguna, Spain.
One of the most important steps in preclinical drug discovery is to demonstrate the in vivo efficacy of potential leishmanicidal compounds and good characteristics at the level of parasite killing prior to initiating human clinical trials. This paper describes the use of dehydrothyrsiferol (DT), isolated from the red alga , in a pharmaceutical form supported on Sepigel, and the in vivo efficacy against a mouse model of cutaneous leishmaniasis. Studying the ultrastructural effect of DT was also carried out to verify the suspected damage at the cellular level and determine the severity of damages produced in the homeostasis of promastigotes.
View Article and Find Full Text PDFPretreatment with serine protease inhibitors impairs Leishmania amazonensis survival on macrophages.
Parasit Vectors
January 2025
Laboratório de Imunologia Clínica, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz-Fiocruz, Rio de Janeiro, RJ, 21040-360, Brazil.
Background: Leishmaniases are neglected tropical diseases with great clinical and epidemiological importance. The current chemotherapy available for the treatment of leishmaniasis presents several problems, such as adverse effects, toxicity, long treatment time, and parasite resistance. The discovery of new therapeutic alternatives is extremely essential, and the discovery of cellular targets is a tool that helps in the development of new drugs.
View Article and Find Full Text PDFAntiparasitic Activities of Plants from the Traditional Senegalese Pharmacopoeia: Isolation of Antitrypanosomal and Antileishmanial ellagic acid derivatives from Terminalia avicennioides.
Chem Biodivers
January 2025
University of Lille: Universite de Lille, UMR BioEcoAgro, 3 rue du Professeur Laguesse, 59800, LILLE, FRANCE.
Parasitic diseases such as trypanosomiasis and leishmaniasis pose significant health challenges in Africa. The Senegalese Pharmacopoeia, known for its many medicinal plants with anti-infectious properties, can be a source of antiparasitic natural products. This study aimed to evaluate the in vitro antiparasitic activities of 33 methanolic extracts from 24 ethnopharmacologically selected plants against Trypanosoma brucei brucei and Leishmania mexicana mexicana, as well as their cytotoxic activities on WI-38 cells.
View Article and Find Full Text PDFImmunomodulatory properties of extracellular vesicles containing the Spike protein of SARS-CoV-2.
Front Parasitol
April 2024
INRS- Centre Armand-Frappier Santé Biotechnologie, Université du Québec, Laval, QC, Canada.
Extracellular vesicles released by the protozoan parasite display immunomodulatory properties towards mammalian immune cells. In this study, we have evaluated the potential of extracellular vesicles derived from the non-pathogenic protozoan towards the development of a vaccine adjuvant. As a proof of concept, we expressed in a codon-optimized SARS-CoV-2 Spike protein fused to the secreted acid phosphatase signal peptide in the N-terminal and to a 6×-His stretch in the C-terminal.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!