A new oral self-emulsifying drug delivery system improves the antileishmania efficacy of fexinidazole in vivo

Damasio, Danielle Sóter do Nascimento; Antunes, Patrícia Andrade; Lages, Eduardo Burgarelli; Morais-Teixeira, Eliane de; Vital, Kátia Duarte; Cardoso, Valbert Nascimento; Fernandes, Simone Odília Antunes; Aguiar, Marta Gontijo; Ferreira, Lucas Antônio Miranda

doi:10.1016/j.ijpharm.2022.122505

Cited by 5 publications

(12 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After homogenization, the medium-chain triglyceride (MTC) (Lipoid GmbH, Ludwigshafen, Germany) was added slowly and stirred for another 2 min. As the last step of the process, the formulation was placed in an ultrasound bath for 30 min at 40 °C to obtain an isotropic mixture and then kept under magnetic stirring for 24 ± 2 h at room temperature [ 7 ]. The selection of the components used in the preparation of SEDDS-FEX was carried out considering the toxicity, solvent capacity, miscibility, physical state at room temperature, and stability.…”

Section: Methodsmentioning

confidence: 99%

“…The average diameter and polydispersity index (Pdi) of the systems were investigated via photon correlation spectroscopy, and the zeta potential (ZP) was determined via dynamic light scattering associated with electrophoretic mobility [ 7 , 15 ]. The measurements were performed using Zetasizer Nano ZS90 equipment (Malvern Instruments Ltd., Worcestershire, UK).…”

Section: Methodsmentioning

confidence: 99%

“…The measurements were performed using Zetasizer Nano ZS90 equipment (Malvern Instruments Ltd., Worcestershire, UK). The Lip-ClAlPc and SEDDS-FEX samples were diluted with a sodium chloride 0.9% ( w / v ) solution and Milli-Q water, respectively [ 7 , 15 ]. Measurements are performed in triplicate, and values are represented as mean ± standard deviation.…”

Section: Methodsmentioning

confidence: 99%

“…Fexinidazole (FEX) exhibited activity in vitro and in vivo, demonstrating its potential in the oral therapy of leishmaniasis [ 5 , 6 , 7 ]. However, FEX is sparingly soluble in water, which can be a limiting factor for its oral absorption.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Combination of the Topical Photodynamic Therapy of Chloroaluminum Phthalocyanine Liposomes with Fexinidazole Oral Self-Emulsifying System as a New Strategy for Cutaneous Leishmaniasis Treatment

Silva,

Damasio,

Coelho

et al. 2024

Pharmaceutics

Self Cite

View full text Add to dashboard Cite

Cutaneous leishmaniasis (CL) is a neglected tropical disease. The treatment is restricted to drugs, such as meglumine antimoniate and amphotericin B, that exhibit toxic effects, high cost, long-term treatment, and limited efficacy. The development of new alternative therapies, including the identification of effective drugs for the topical and oral treatment of CL, is of great interest. In this sense, a combination of topical photodynamic therapy (PDT) with chloroaluminum phthalocyanine liposomes (Lip-ClAlPc) and the oral administration of a self-emulsifying drug delivery system containing fexinidazole (SEDDS-FEX) emerges as a new strategy. The aim of the present study was to prepare, characterize, and evaluate the efficacy of combined therapy with Lip-ClAlPc and SEDDS-FEX in the experimental treatment of Leishmania (Leishmania) major. Lip-ClAlPc and SEDDS-FEX were prepared, and the antileishmanial efficacy study was conducted with the following groups: 1. Lip-ClAlPc (0.05 mL); 2. SEDDS-FEX (50 mg/kg/day); 3. Lip-ClAlPc (0.05 mL)+SEDDS-FEX (50 mg/kg/day) combination; 4. FEX suspension (50 mg/kg/day); and 5. control (untreated). BALB/c mice received 10 sessions of topical Lip-ClAlPc on alternate days and 20 consecutive days of SEDDS-FEX or FEX oral suspension. Therapeutical efficacy was evaluated via the parasite burden (limiting-dilution assay), lesion size (mm), healing of the lesion, and histological analyses. Lip-ClAlPc and SEDDS-FEX presented physicochemical characteristics that are compatible with the administration routes used in the treatments. Lip-ClAlPc+SEDDS-FEX led to a significant reduction in the parasitic burden in the lesion and spleen when compared to the control group (p < 0.05) and the complete healing of the lesion in 43% of animals. The Lip-ClAlPc+SEDDS-FEX combination may be promising for the treatment of CL caused by L. major.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Combination of the Topical Photodynamic Therapy of Chloroaluminum Phthalocyanine Liposomes with Fexinidazole Oral Self-Emulsifying System as a New Strategy for Cutaneous Leishmaniasis Treatment

Silva,

Damasio,

Coelho

et al. 2024

Pharmaceutics

Self Cite

View full text Add to dashboard Cite

show abstract

“…SEDDS may be used as an alternative to conventional formulations due to their lipophilic nature, which eventually addresses the liabilities of a drug, such as poor solubility, bioavailability, instability, and low oral absorption. [25][26][27][28][29] Briefly, the reason for improved dissolution and bioavailability from SEDDS could be via the formation of fine emulsion in the GIT. The drug is in the dissolved state in the formulation, eliminating the dissolution step upon oral administration.…”

Section: Introductionmentioning

confidence: 99%

Self‐Emulsifying Drug Delivery of Khellin for Improving Its Oral Bioavailability

Shah,

Wazir,

Nandi

et al. 2023

ChemistrySelect

View full text Add to dashboard Cite

Self‐emulsifying drug delivery system (SEDDS) is extensively used for enhancing the solubility, dissolution, and pharmacokinetics of poorly soluble drugs. Khellin is a natural product with multiple pharmacological activities and has inspired the discovery of two first‐in‐class drugs, amiodarone hydrochloride and sodium cromoglycate. The poor‐aqueous solubility is one of the limitations in developing this molecule. Herein, we aimed to improve the drug loading of khellin by developing its SEDDS formulation. A combination of castor oil, tetraethylene glycol, and Transcutol HP (10 : 30 : 60 v/v) was identified, inhibiting the drug‘s precipitation post‐dilution in an aqueous media. The optimized formulation, SB‐16KD, was characterized using 1H NMR, DSC, and FTIR to understand khellin‘s physical/chemical interaction with the formulation excipients. The in vitro dissolution studies of khellin in SB‐16KD correlated well with the oral pharmacokinetics in Wistar rats (1.6 vs. 1.7‐fold). The comparative oral pharmacokinetics of formulation against native khellin was performed at 45 mg/kg in Wistar rats. The results were promising, with 1.7‐fold higher plasma exposure by SEDDS formulation. Hence, the results warrant further developmental studies on SEDDS in dose reduction.

show abstract

Free Radical Production Induced by Nitroimidazole Compounds Lead to Cell Death in Leishmania infantum Amastigotes

Andrés-Rodríguez,

González-Montero,

García-Fernández

et al. 2024

Molecules

View full text Add to dashboard Cite

Leishmania infantum is the vector-borne trypanosomatid parasite causing visceral leishmaniasis in the Mediterranean basin. This neglected tropical disease is treated with a limited number of obsolete drugs that are not exempt from adverse effects and whose overuse has promoted the emergence of resistant pathogens. In the search for novel antitrypanosomatid molecules that help overcome these drawbacks, drug repurposing has emerged as a good strategy. Nitroaromatic compounds have been found in drug discovery campaigns as promising antileishmanial molecules. Fexinidazole (recently introduced for the treatment of stages 1 and 2 of African trypanosomiasis), and pretomanid, which share the nitroimidazole nitroaromatic structure, have provided antileishmanial activity in different studies. In this work, we have tested the in vitro efficacy of these two nitroimidazoles to validate our 384-well high-throughput screening (HTS) platform consisting of L. infantum parasites emitting the near-infrared fluorescent protein (iRFP) as a biomarker of cell viability. These molecules showed good efficacy in both axenic and intramacrophage amastigotes and were poorly cytotoxic in RAW 264.7 and HepG2 cultures. Fexinidazole and pretomanid induced the production of ROS in axenic amastigotes but were not able to inhibit trypanothione reductase (TryR), thus suggesting that these compounds may target thiol metabolism through a different mechanism of action.

show abstract

A new oral self-emulsifying drug delivery system improves the antileishmania efficacy of fexinidazole in vivo

Cited by 5 publications

References 39 publications

Combination of the Topical Photodynamic Therapy of Chloroaluminum Phthalocyanine Liposomes with Fexinidazole Oral Self-Emulsifying System as a New Strategy for Cutaneous Leishmaniasis Treatment

Combination of the Topical Photodynamic Therapy of Chloroaluminum Phthalocyanine Liposomes with Fexinidazole Oral Self-Emulsifying System as a New Strategy for Cutaneous Leishmaniasis Treatment

Self‐Emulsifying Drug Delivery of Khellin for Improving Its Oral Bioavailability

Free Radical Production Induced by Nitroimidazole Compounds Lead to Cell Death in Leishmania infantum Amastigotes

Contact Info

Product

Resources

About