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Unmet clinical needs in the treatment of systemic fungal infections: The role of amphotericin B and drug targeting.
Int J Pharm. 2017 Jun 15; 525(1):139-148.IJ

Abstract

Recently an increase in both the prevalence and incidence of invasive fungal infections have been reported. The number of fungal species that can cause systemic mycoses are higher and current antifungal therapies are still far from ideal. The emergence of antifungal resistances has a major clinical impact when using azoles and echinocandins leading to possible treatment failure and ultimately putting the patient's life at risk. Amphotericin B can play a key role in treating severe invasive mycoses as the incidence of antifungal resistance is very low combined with a high efficacy against a wide range of fungi. However, the use of this drug is limited due to its high toxicity and the infusion-related side effects often necessitating patient hospitalisation. New medicines based on lipid-based systems have been commercialised in the last decade, these treatments are able to reduce the toxicity of the drug but intravenous administration is still required. An oral or topically self-administered amphotericin B formulation can overcome these challenges, however such a product is not yet available. Several drug delivery systems such as cochleates, nanoparticulate and self-emulsifying systems are under development in order to enhance the solubility of the drug in aqueous media and promote oral absorption and cutaneous permeation across the skin. In this review, the type of drug delivery system and the effect of particle size on efficacy, toxicity and biodistribution will be discussed.

Authors+Show Affiliations

Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid,Plaza Ramón y Cajal s/n, 28040 Madrid, Spain.Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid,Plaza Ramón y Cajal s/n, 28040 Madrid, Spain.Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid,Plaza Ramón y Cajal s/n, 28040 Madrid, Spain; Instituto Universitario de Farmacia Industrial (IUFI), Facultad de Farmacia, Universidad Complutense de Madrid, Avenida Complutense, 28040 Madrid, Spain.Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid,Plaza Ramón y Cajal s/n, 28040 Madrid, Spain; Instituto Universitario de Farmacia Industrial (IUFI), Facultad de Farmacia, Universidad Complutense de Madrid, Avenida Complutense, 28040 Madrid, Spain. Electronic address: drserran@ucm.es.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

28400291

Citation

Fernández-García, Raquel, et al. "Unmet Clinical Needs in the Treatment of Systemic Fungal Infections: the Role of Amphotericin B and Drug Targeting." International Journal of Pharmaceutics, vol. 525, no. 1, 2017, pp. 139-148.
Fernández-García R, de Pablo E, Ballesteros MP, et al. Unmet clinical needs in the treatment of systemic fungal infections: The role of amphotericin B and drug targeting. Int J Pharm. 2017;525(1):139-148.
Fernández-García, R., de Pablo, E., Ballesteros, M. P., & Serrano, D. R. (2017). Unmet clinical needs in the treatment of systemic fungal infections: The role of amphotericin B and drug targeting. International Journal of Pharmaceutics, 525(1), 139-148. https://doi.org/10.1016/j.ijpharm.2017.04.013
Fernández-García R, et al. Unmet Clinical Needs in the Treatment of Systemic Fungal Infections: the Role of Amphotericin B and Drug Targeting. Int J Pharm. 2017 Jun 15;525(1):139-148. PubMed PMID: 28400291.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Unmet clinical needs in the treatment of systemic fungal infections: The role of amphotericin B and drug targeting. AU - Fernández-García,Raquel, AU - de Pablo,Esther, AU - Ballesteros,María Paloma, AU - Serrano,Dolores R, Y1 - 2017/04/08/ PY - 2017/02/03/received PY - 2017/04/04/revised PY - 2017/04/06/accepted PY - 2017/4/13/pubmed PY - 2018/1/9/medline PY - 2017/4/13/entrez KW - AmBisome(®) KW - Amphotericin B KW - Candida spp KW - Drug delivery KW - Nanoparticles KW - Nephrotoxicity KW - Poly-aggregates SP - 139 EP - 148 JF - International journal of pharmaceutics JO - Int J Pharm VL - 525 IS - 1 N2 - Recently an increase in both the prevalence and incidence of invasive fungal infections have been reported. The number of fungal species that can cause systemic mycoses are higher and current antifungal therapies are still far from ideal. The emergence of antifungal resistances has a major clinical impact when using azoles and echinocandins leading to possible treatment failure and ultimately putting the patient's life at risk. Amphotericin B can play a key role in treating severe invasive mycoses as the incidence of antifungal resistance is very low combined with a high efficacy against a wide range of fungi. However, the use of this drug is limited due to its high toxicity and the infusion-related side effects often necessitating patient hospitalisation. New medicines based on lipid-based systems have been commercialised in the last decade, these treatments are able to reduce the toxicity of the drug but intravenous administration is still required. An oral or topically self-administered amphotericin B formulation can overcome these challenges, however such a product is not yet available. Several drug delivery systems such as cochleates, nanoparticulate and self-emulsifying systems are under development in order to enhance the solubility of the drug in aqueous media and promote oral absorption and cutaneous permeation across the skin. In this review, the type of drug delivery system and the effect of particle size on efficacy, toxicity and biodistribution will be discussed. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/28400291/Unmet_clinical_needs_in_the_treatment_of_systemic_fungal_infections:_The_role_of_amphotericin_B_and_drug_targeting L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(17)30294-6 DB - PRIME DP - Unbound Medicine ER -