Method validation and nanoparticle characterization assays for an innovative amphothericin B formulation to reach increased stability and safety in infectious diseases

Tadini, Maraine Catarina; Pinheiro, Ana Maria de Freitas; Carrão, Daniel Blascke; Forte, Ana Luiza Scarano Aguillera; Nikolaou, Sofia; Oliveira, Anderson Rodrigo Moraes de; Berretta, Andresa Aparecida; Marquele-Oliveira, Franciane

doi:10.1016/j.jpba.2017.06.034

Cited by 8 publications

(8 citation statements)

References 22 publications

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“…A previously established proportion of ingredients was used to formulate AmB-NLC. 16 Initially, NLC was produced by hot microemulsion (65 ± 5°C), consisting of a blend of liquid and solid lipids, a surfactant and co-surfactants, using the method described by Tadini et al 16 , 21 To obtain AmB-NLC, amphotericin B (0.1%) and the antioxidant (0.005%) were added to a hot microemulsion under stirring at 150 rpm. The microemulsion containing the drug was then diluted in cold water (1–4°C) under homogenization (IKA - TURRAX T25).…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…C TotalAmb , referring to the total mass of amphotericin B in the suspension of AmB-NLC, was quantified using the analytical curve. Entrapment efficiency was calculated using the equation below: 16 …”

Section: Methodsmentioning

confidence: 99%

“…The analysis employed herein was performed using a HPLC-DAD (Shimadzu, Kyoto, Japan) in accordance with the method previously described by Tadini et al, which was previously validated by our group in accordance with the European Medicines Agency (EMA) guideline on Bioanalytical Method Validation. 16,23 The guard column (3.0 mm x 4.6mm, 2.7 µm) was coupled to a Ascentis Express Fused Core C 18 chromatographic column (100 mm x 4.6 mm, 2.7 µm), both acquired from Supelco (St. Louis, MO, USA). Analyses were carried out at 30°C under ambient yellow light.…”

Section: Drug Contentmentioning

confidence: 99%

“…14,15 The development and characterization of AmB-NLC has been previously demonstrated by our group, with outstanding results achieved in terms of sustained release and reduced AmB cytotoxicity, probably related to the polyaggregate drug form. 16 The particle presents a sustained controlled release profile of up 46 h at pH 7.4, with faster disruption in acidic environments (pH 5), and presents a target-driven effect due to the phospholipid nanoparticle composition employed. In this context, AmB-NLC represents an innovative new approach to AmB treatment in leishmaniasis and fungal infections.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of in vitro and in vivo Efficacy of a Novel Amphotericin B-Loaded Nanostructured Lipid Carrier in the Treatment of Leishmania braziliensis Infection

Rebouças-Silva¹,

Tadini²,

Devequi-Nunes³

et al. 2020

IJN

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Background Leishmaniasis is a neglected disease, and the current therapeutic arsenal for its treatment is seriously limited by high cost and toxicity. Nanostructured lipid carriers (NLCs) represent a promising approach due to high drug loading capacity, controlled drug release profiles and superior stability. Here, we explore the efficacy of a unique pH-sensitive amphotericin B-loaded NLC (AmB-NLC) in Leishmania braziliensis infection in vitro and in vivo. Methods and Results AmB-NLC was assessed by dynamic light scattering and atomic force microscopy assays. The carrier showed a spherical shape with a nanometric size of 242.0 ± 18.3 nm. Zeta potential was suggestive of high carrier stability (−42.5 ± 1.5 mV), and the NLC showed ~99% drug encapsulation efficiency (EE%). In biological assays, AmB-NLC presented a similar IC 50 as free AmB and conventional AmB deoxycholate (AmB-D) (11.7 ± 1.73; 5.3 ± 0.55 and 13 ± 0.57 ng/mL, respectively), while also presenting higher selectivity index and lower toxicity to host cells, with no observed production of nitric oxide or TNF-α by in vitro assay. Confocal microscopy revealed the rapid uptake of AmB-NLC by infected macrophages after 1h, which, in association with more rapid disruption of AmB-NLC at acidic pH levels, may directly affect intracellular parasites. Leishmanicidal effects were evaluated in vivo in BALB/c mice infected in the ear dermis with L. braziliensis and treated with a pentavalent antimonial (Sb 5+ ), liposomal AmB (AmB-L) or AmB-NLC. After 6 weeks of infection, AmB-NLC treatment resulted in smaller ear lesion size in all treated mice, indicating the efficacy of the novel formulation. Conclusion Here, we preliminarily demonstrate the effectiveness of an innovative and cost-effective AmB-NLC formulation in promoting the killing of intracellular L. braziliensis . This novel carrier system could be a promising alternative for the future treatment of cutaneous leishmaniasis.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Drug Contentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evaluation of in vitro and in vivo Efficacy of a Novel Amphotericin B-Loaded Nanostructured Lipid Carrier in the Treatment of Leishmania braziliensis Infection

Rebouças-Silva¹,

Tadini²,

Devequi-Nunes³

et al. 2020

IJN

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Sixty years of Amphotericin B: An Overview of the Main Antifungal Agent Used to Treat Invasive Fungal Infections

Cavassin

Baú-Carneiro²,

Vilas-Boas³

et al. 2021

Infect Dis Ther

165

123

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Introduced in the late 1950s, polyenes represent the oldest family of antifungal drugs. The discovery of amphotericin B and its therapeutic uses is considered one of the most important scientific milestones of the twentieth century . Despite its toxic potential, it remains useful in the treatment of invasive fungal diseases owing to its broad spectrum of activity, low resistance rate, and excellent clinical and pharmacological action. The well-reported and defined toxicity of the conventional drug has meant that much attention has been paid to the development of new products that could minimize this effect. As a result, lipid-based formulations of amphotericin B have emerged and, even keeping the active principle in common, present distinct characteristics that may influence therapeutic results. This study presents an overview of the pharmacological properties of the different formulations for systemic use of amphotericin B available for the treatment of invasive fungal infections, highlighting the characteristics related to their chemical, pharmacokinetic structures, drug–target interactions, stability, and others, and points out the most relevant aspects for clinical practice.

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Pharmacokinetic study of AmB-NP-GR: A new granule form with amphotericin B to treat leishmaniasis and fungal infections

Tadini

Fernandes

Ozelin

et al. 2022

European Journal of Pharmaceutical Sciences

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Method validation and nanoparticle characterization assays for an innovative amphothericin B formulation to reach increased stability and safety in infectious diseases

Cited by 8 publications

References 22 publications

<p>Evaluation of in vitro and in vivo Efficacy of a Novel Amphotericin B-Loaded Nanostructured Lipid Carrier in the Treatment of <em>Leishmania braziliensis</em> Infection</p>

<p>Evaluation of in vitro and in vivo Efficacy of a Novel Amphotericin B-Loaded Nanostructured Lipid Carrier in the Treatment of <em>Leishmania braziliensis</em> Infection</p>

Sixty years of Amphotericin B: An Overview of the Main Antifungal Agent Used to Treat Invasive Fungal Infections

Pharmacokinetic study of AmB-NP-GR: A new granule form with amphotericin B to treat leishmaniasis and fungal infections

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