Fungal diseases: could nanostructured drug delivery systems be a novel paradigm for therapy?

Voltan, Aline Raquel; Quindós, Guillermo; Alarcón, Kaila Petronila Medina; Fusco‐Almeida, Ana Marisa; Mendes-Giannini, María José Soares; Chorilli, Marlus

doi:10.2147/ijn.s93105

Cited by 99 publications

(70 citation statements)

References 204 publications

(124 reference statements)

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“…Clinically, the intravenous dosage form of AmB-deoxycholate has adverse effects, mainly nephrotoxicity. The synthesis of AmB analogs such as AmB esters or a preparation including an AmB lipid complex, AmB colloidal dispersion, liposomal AmB and intralipid AmB have been generated to improve the therapeutic index and lower toxicity (Gupta and Tomas, 2003; Vyas and Gupta, 2006; Voltan et al, 2016). …”

Section: New Antifungal Formulations and New Antifungal Drug Structurmentioning

confidence: 99%

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Antifungal Therapy: New Advances in the Understanding and Treatment of Mycosis

et al. 2017

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The high rates of morbidity and mortality caused by fungal infections are associated with the current limited antifungal arsenal and the high toxicity of the compounds. Additionally, identifying novel drug targets is challenging because there are many similarities between fungal and human cells. The most common antifungal targets include fungal RNA synthesis and cell wall and membrane components, though new antifungal targets are being investigated. Nonetheless, fungi have developed resistance mechanisms, such as overexpression of eﬄux pump proteins and biofilm formation, emphasizing the importance of understanding these mechanisms. To address these problems, different approaches to preventing and treating fungal diseases are described in this review, with a focus on the resistance mechanisms of fungi, with the goal of developing efficient strategies to overcoming and preventing resistance as well as new advances in antifungal therapy. Due to the limited antifungal arsenal, researchers have sought to improve treatment via different approaches, and the synergistic effect obtained by the combination of antifungals contributes to reducing toxicity and could be an alternative for treatment. Another important issue is the development of new formulations for antifungal agents, and interest in nanoparticles as new types of carriers of antifungal drugs has increased. In addition, modifications to the chemical structures of traditional antifungals have improved their activity and pharmacokinetic parameters. Moreover, a different approach to preventing and treating fungal diseases is immunotherapy, which involves different mechanisms, such as vaccines, activation of the immune response and inducing the production of host antimicrobial molecules. Finally, the use of a mini-host has been encouraging for in vivo testing because these animal models demonstrate a good correlation with the mammalian model; they also increase the speediness of as well as facilitate the preliminary testing of new antifungal agents. In general, many years are required from discovery of a new antifungal to clinical use. However, the development of new antifungal strategies will reduce the therapeutic time and/or increase the quality of life of patients.

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Section: New Antifungal Formulations and New Antifungal Drug Structurmentioning

confidence: 99%

“…These delivery systems are able to improve bioavailability and reduce toxicity and present specificity for target tissues; however, there is an associated high cost of production (Vyas and Gupta, 2006; Sato et al, 2015; Voltan et al, 2016). …”

Section: New Antifungal Formulations and New Antifungal Drug Structurmentioning

confidence: 99%

Antifungal Therapy: New Advances in the Understanding and Treatment of Mycosis

et al. 2017

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“…The Q and GA co-loaded liposomes (LP-Q+GA) were prepared by a film hydration method as previously described [25], with some modifications. Briefly, Q (10 mg) and SPC (200 mg) were dissolved in 10 mL of methanol in a round-bottom flask.…”

Section: Preparation Of Liposomesmentioning

confidence: 99%

“…The purpose was to obtain a formulation able to guarantee a modified release of both active compounds, thus assuring adequate concentration of polyphenols in the vaginal mucosa. Liposomes are vesicular nanostructures composed of one or more lipid bilayers, and are particularly suitable for the combined delivery of two molecules with different physicochemical properties since they are able to accommodate both the lipophilic compounds, such as quercetin, and more hydrophilic substances, such as gallic acid, inside the lipid and aqueous compartments, respectively [24,25].…”

Section: Introductionmentioning

confidence: 99%

Utilizing Liposomal Quercetin and Gallic Acid in Localized Treatment of Vaginal Candida Infections

et al. 2019

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Vulvovaginal candidiasis (VVC) is a widely spread fungal infection that causes itching, pain and inflammation at the vaginal site. Although common, currently available treatment suffers from limited efficacy and high recurrence. In addition, the growing problem of resistance to azole drugs used in current treatments emphasizes the need for superior treatment options. Antimicrobial polyphenols are an attractive approach offering multitargeting therapy. We aimed to develop novel liposomes for simultaneous delivery of two polyphenols (quercetin, Q, and gallic acid, GA) that, when released within the vaginal cavity, act in synergy to eradicate infection while alleviating the symptoms of VVC. Q was selected for its anti-itching and anti-inflammatory properties, while GA for its reported activity against Candida. Novel liposomes containing only Q (LP-Q), only GA (LP-GA) or both polyphenols (LP-Q+GA) were in the size range around 200 nm. Q was efficiently entrapped in both LP-Q and in LP-Q+GA (85%) while the entrapment of GA was higher in LP-Q+GA (30%) than in LP-GA (25%). Liposomes, especially LP-Q+GA, promoted sustained release of both polyphenols. Q and GA acted in synergy, increasing the antioxidant activities of a single polyphenol. Polyphenol-liposomes were not cytotoxic and displayed stronger anti-inflammatory effects than free polyphenols. Finally, LP-GA and LP-Q+GA considerably reduced C. albicans growth.

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“…Nowadays, a great number of antifungal moieties is available and is capable of treating infections which were considered to be fatal in the past. However, treatment of fungal infections is facing great challenges due to the development of resistance to old as well as new drugs (Voltan et al, 2016). Concerns remain regarding the toxicity, low bioavailability, and lack of efficacy of antifungal agents.…”

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confidence: 99%

Nanotherapeutics as promising approaches to combat fungal infections

Kamel

2019

Drug Development Research

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Fungal infections are a serious and growing public health problem. Invasive fungal infections can increase the rate of morbidity and mortality of immune-compromised patients. Nowadays, there are a great number of antifungal agents; however, the control of fungal diseases is unsatisfactory due to lack of treatment efficiency, low drug biovailability, high drug toxicity, and emergence of fungal resistance. The use of advanced drug delivery systems can hopefully revolutionize the treatment of fungal diseases. This article comprises an overview on antifungal drugs, plant-derived moieties with antifungal activity, together with the encountered problems. The nanoencapsulation of antifungal agents is proposed as a potential successful therapeutic approach by enhancing the solubility and stability of the active constituents, extending the biological effect, improving the absorption, and adjusting the degree of hydrophilicity/lipophilicity. In addition, some antifungal market products based on the nanotechnology are displayed. K E Y W O R D Sdrugs, efficacy and safety, fungal, herbal, nanoparticles

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Fungal diseases: could nanostructured drug delivery systems be a novel paradigm for therapy?

Cited by 99 publications

References 204 publications

Antifungal Therapy: New Advances in the Understanding and Treatment of Mycosis

Antifungal Therapy: New Advances in the Understanding and Treatment of Mycosis

Utilizing Liposomal Quercetin and Gallic Acid in Localized Treatment of Vaginal Candida Infections

Nanotherapeutics as promising approaches to combat fungal infections

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