&lt;I&gt;In Vitro&lt;/I&gt; Antifungal Activity and Toxicity of Itraconazole in DMSA-PLGA Nanoparticles

Cunha-Azevedo, Elaine P.; Silva, Jaqueline R.; Martins, Olímpia Paschoal; Siqueira-Moura, Marigilson P.; Bocca, Anamélia Lorenzetti; Felipe, Maria Sueli Soares; Tedesco, Antônio Cláudio; Azevedo, Ricardo Bentes

doi:10.1166/jnn.2011.3576

Cited by 19 publications

(7 citation statements)

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“…It has become apparent that the development of nanotechnology for the treatment of infectious diseases, particularly skin disease, involves two major areas: The first utilizes materials that at the nanoscale have inherent antimicrobial properties (Hemmila et al, 2010), and the second incorporates known therapeutics into nano-vehicles in order to enhance delivery and improve efficacy (Cunha-Azevedo et al, 2011; Dominguez-Delgado et al, 2011; Kumar et al, 2011). The ideal approach to develop a topical therapy for microbial infection in skin would utilize a nanomaterial that has both inherent and potent antimicrobial properties and the ability to serve as a nano-vehicle would be ideal.…”

Section: Introductionmentioning

confidence: 99%

Antimicrobial and Anti-Inflammatory Activity of Chitosan–Alginate Nanoparticles: A Targeted Therapy for Cutaneous Pathogens

Friedman

Phan

Schairer

et al. 2013

Journal of Investigative Dermatology

280

143

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Advances in nanotechnology have demonstrated potential application of nanoparticles for effective and targeted drug delivery. Here, we investigated the antimicrobial and immunological properties and the feasibility of using nanoparticles to deliver antimicrobial agents to treat a cutaneous pathogen. Nanoparticles synthesized with chitosan and alginate demonstrated a direct antimicrobial activity in vitro against Propionibacterium acnes, the bacterium linked to the pathogenesis of acne. By electron microscopy imaging, chitosan-alginate nanoparticles were found to induce disruption of the P. acnes cell membrane, providing a mechanism for the bactericidal effect. The chitosan-alginate nanoparticles also exhibited anti-inflammatory properties as they inhibited P. acnes induced inflammatory cytokine production in human monocytes and keratinocytes. Furthermore, benzoyl peroxide, a commonly used anti-acne drug, was effectively encapsulated in the chitosan-alginate nanoparticles and demonstrated superior antimicrobial activity against P. acnes compared to benzoyl peroxide alone while demonstrating less toxicity to eukaryotic cells. Together, these data suggest the potential utility of topical delivery of chitosan-alginate nanoparticle encapsulated drug therapy for the treatment of dermatologic conditions with infectious and inflammatory components.

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Section: Introductionmentioning

confidence: 99%

Antimicrobial and Anti-Inflammatory Activity of Chitosan–Alginate Nanoparticles: A Targeted Therapy for Cutaneous Pathogens

Friedman

Phan

Schairer

et al. 2013

Journal of Investigative Dermatology

280

143

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“…Only a few groups previously reported PLGA-ITZ nanoparticles for in vitro antifungal activity, [13][14][15] but their formulations were not systematically characterized for in vivo study, and no pharmacokinetics have ever been completed to explore the formulation's capability of intravenous injection and sustained release. We herein synthesized, characterized, and optimized the formulation for parenteral administration.…”

mentioning

confidence: 99%

Development of PLGA-based itraconazole injectable nanospheres for sustained release

Bian¹,

Liang²,

John³

et al. 2013

IJN

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Purpose Itraconazole (ITZ) is a synthetic triazole antifungal agent, which is widely used for treatment and prevention of fungal infections. The purpose of this study is to develop ITZ-loaded poly(lactic-co-glycolic acid) (PLGA) nanospheres (PLGA-ITZ-NS) as a new sustained-release formulation for intravenous ITZ administration. Materials and methods PLGA-ITZ-NS were prepared by a nanoprecipitation method and optimized by modifying the surfactant poloxamer 188 concentration and PLGA:ITZ ratio. Their physicochemical properties, including size, zeta potential, external morphology and encapsulation efficiency, were characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM) and high performance liquid chromatography (HPLC). The effect of the different selected lyoprotectants with various concentrations on NS particles size and surface charge were also assessed. Rapid and sensitive HPLC and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods were developed to determine ITZ concentrations in formulation and in rat plasma, respectively. Pharmacokinetics of the optimum PLGA-ITZ-NS formulation was compared with the former commercial Sporanox® injection formulation using rats as the animal model. Noncompartmental pharmacokinetic parameters were obtained by WinNonlin® software. Results Optimal PLGA-ITZ-NS had a mean particle size of about 200 nm with a high homogeneity (polydispersity index ≈0.2), favorable zeta potential (approximately −20 to −30 mV) and encapsulation efficiency (72%). In addition, 2% w/v sucrose was selected as a lyoprotectant for NS freeze-drying. The newly developed LC-MS/MS assay was validated and found to be accurate and precise. The in vivo study showed that the NS formulation has a similar systemic bioavailability to Sporanox® while providing a sustained plasma level (> 100 ng/mL) for up to 24 hours after intravenous administration. Conclusion Our newly developed PLGA-ITZ-NS has shown great sustained release and comparable bioavailability with Sporanox®, therefore having the potential to be an alternative injectable formulation of ITZ.

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“…A subsequent study showed that the nano-D-AMB is highly captured in the lungs, liver, and spleen of mice (Souza et al, 2015). DMSA-PLGA NPs loaded with ITZ have also been studied against P. brasiliensis and the PLGA-ITZ had lower MICs compared to ITZ alone with less cytotoxicity compared to the free drug (Cunha-Azevedo et al, 2011). Gallic acid is a secondary metabolite derived from plants such as Paeonia rockii, Astronium sp., and Syzygium cumini, among others.…”

Section: Aspergillosismentioning

confidence: 99%

Therapies and Vaccines Based on Nanoparticles for the Treatment of Systemic Fungal Infections

Kischkel

Rossi

Santos

et al. 2020

Front. Cell. Infect. Microbiol.

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Treatment modalities for systemic mycoses are still limited. Currently, the main antifungal therapeutics include polyenes, azoles, and echinocandins. However, even in the setting of appropriate administration of antifungals, mortality rates remain unacceptably high. Moreover, antifungal therapy is expensive, treatment periods can range from weeks to years, and toxicity is also a serious concern. In recent years, the increased number of immunocompromised individuals has contributed to the high global incidence of systemic fungal infections. Given the high morbidity and mortality rates, the complexity of treatment strategies, drug toxicity, and the worldwide burden of disease, there is a need for new and efficient therapeutic means to combat invasive mycoses. One promising avenue that is actively being pursued is nanotechnology, to develop new antifungal therapies and efficient vaccines, since it allows for a targeted delivery of drugs and antigens, which can reduce toxicity and treatment costs. The goal of this review is to discuss studies using nanoparticles to develop new therapeutic options, including vaccination methods, to combat systemic mycoses caused by Candida sp., Cryptococcus sp., Paracoccidioides sp., Histoplasma sp., Coccidioides sp., and Aspergillus sp., in addition to providing important information on the use of different types of nanoparticles, nanocarriers and their corresponding mechanisms of action.

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<I>In Vitro</I> Antifungal Activity and Toxicity of Itraconazole in DMSA-PLGA Nanoparticles

Cited by 19 publications

References 0 publications

Antimicrobial and Anti-Inflammatory Activity of Chitosan–Alginate Nanoparticles: A Targeted Therapy for Cutaneous Pathogens

Antimicrobial and Anti-Inflammatory Activity of Chitosan–Alginate Nanoparticles: A Targeted Therapy for Cutaneous Pathogens

Development of PLGA-based itraconazole injectable nanospheres for sustained release

Therapies and Vaccines Based on Nanoparticles for the Treatment of Systemic Fungal Infections

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