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Pharmaceutics
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Antifungal and Antiparasitic Drug Delivery Volume II
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Antifungal and Antiparasitic Drug Delivery Volume II

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Pharmaceutical Technology, Manufacturing and Devices".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 28851

Special Issue Editors

Prof. Dr. Juan José Torrado Durán

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Guest Editor
Pharmaceutics and Food Technology, School of Pharmacy, Complutense University of Madrid, Madrid, Spain
Interests: conventional pharmaceutical dosage forms (tablets, capsules, semisolid and liquid formulations); new controlled release systems (pellets, nanoparticles, microcapsules, microspheres and liposomes) including production and quality control
Special Issues, Collections and Topics in MDPI journals
Dr. Dolores R. Serrano

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Guest Editor
Departament of Pharmaceutics and Food Technology, School of Pharmacy, University Complutense, Avenida Complutense, 28040 Madrid, Spain
Interests: nanomedicines; microparticles; sustained-release formulations; liposomes; nanoparticles; drug targeting; pharmacokinetics
Special Issues, Collections and Topics in MDPI journals
Dr. Javier Capilla

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Guest Editor
Unitat de Microbiologia, Facultat de Medicina i Ciènces de la Salut, Universitat Rovira i Virgili and Institut d'Investigatió Sanitaria Pere Virgili (IISPV), Reus, Spain
Interests: the study and development of antifungal therapies against opportunistic fungal infections as well as virulence factors of fungi causing human infections
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Fungal and parasitic diseases affect more than a billion people across the globe, one-sixth of the world´s population, mostly located in developing countries. The lack of effective and safer treatments combined with a deficient diagnosis lead to serious chronic illness or even death. There is a mismatch between the rate of drug resistance and the development of new medicines. Formulation of antifungal and antiparasitic drugs adapted to different administration routes is challenging bearing in mind their poor water solubility, which limits their bioavailability and efficacy. Hence, there is an unmet clinical need to develop vaccines and novel formulations and drug delivery strategies that can improve the bioavailability and therapeutic effect by enhancing their dissolution, increasing their chemical potency, stabilising the drug and targeting high concentration of drug to the infection sites. In this issue, an update on novel drug delivery strategies of antifungal and antiparasitic drugs to treat both topical and systemic infections will be discussed.

Prof. Dr. Juan José Torrado Durán
Prof. Dr. Dolores R. Serrano
Dr. Javier Capilla
Guest Editors

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Keywords

  • liposomes
  • transferosomes
  • nanoparticles
  • emulsions
  • candidiasis
  • aspergillosis
  • azoles
  • amphotericin B
  • combined therapy
  • quality by design
  • leishmaniasis
  • malaria, trypanosomiais

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Related Special Issue

Published Papers (5 papers)

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Research

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16 pages, 3474 KiB  
Article
Liposomal Ellagic Acid Alleviates Cyclophosphamide-Induced Toxicity and Eliminates the Systemic Cryptococcus neoformans Infection in Leukopenic Mice
by Masood Alam Khan, Arif Khan, Mohd Azam, Khaled S. Allemailem, Faris Alrumaihi, Ahmad Almatroudi, Fahad A. Alhumaydhi, Faizul Azam, Shaheer Hasan Khan, Syeda Fauzia Farheen Zofair, Sumbul Ahmad and Hina Younus
Pharmaceutics 2021, 13(6), 882; https://doi.org/10.3390/pharmaceutics13060882 - 15 Jun 2021
Cited by 12 | Viewed by 2782
Abstract
Cryptococcus neoformans infections rose sharply due to rapid increase in the numbers of immunocompromised individuals in recent years. Treatment of Cryptococcosis in immunocompromised persons is largely very challenging and hopeless. Hence, this study aimed to determine the activity of ellagic acid (EA) in [...] Read more.
Cryptococcus neoformans infections rose sharply due to rapid increase in the numbers of immunocompromised individuals in recent years. Treatment of Cryptococcosis in immunocompromised persons is largely very challenging and hopeless. Hence, this study aimed to determine the activity of ellagic acid (EA) in the treatment of C. neoformans in cyclophosphamide injected leukopenic mice. A liposomal formulation of ellagic acid (Lip-EA) was prepared and characterized, and its antifungal activity was assessed in comparison to fluconazole (FLZ). The efficacy of the drug treatment was tested by assessing survival rate, fungal burden, and histological analysis in lung tissues. The safety of the drug formulations was tested by investigating hepatic, renal function, and antioxidant levels. The results of the present work demonstrated that Lip-EA, not FLZ, effectively eliminated C. neoformans infection in the leukopenic mice. Mice treated with Lip-EA (40 mg/kg) showed 70% survival rate and highly reduced fungal burden in their lung tissues, whereas the mice treated with FLZ (40 mg/kg) had 20% survival rate and greater fungal load in their lungs. Noteworthy, Lip-EA treatment alleviated cyclophosphamide-induced toxicity and restored hepatic and renal function parameters. Moreover, Lip-EA treatment restored the levels of superoxide dismutase and reduced glutathione and catalase in the lung tissues. The effect of FLZ or EA or Lip-EA against C. neoformans infection was assessed by the histological analysis of lung tissues. Lip-EA effectively reduced influx of inflammatory cells, thickening of alveolar walls, congestion, and hemorrhage. The findings of the present study suggest that Lip-EA may prove to be a promising therapeutic formulation against C. neoformans in immunocompromised persons. Full article
(This article belongs to the Special Issue Antifungal and Antiparasitic Drug Delivery Volume II)
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25 pages, 4182 KiB  
Article
Polishing the Therapy of Onychomycosis Induced by Candida spp.: Amphotericin B–Loaded Nail Lacquer
by Aleph M. S. Souza, Renato C. A. Ribeiro, Gleyse K. L. O. Pinheiro, Francisco I. Pinheiro, Wógenes N. Oliveira, Luanda B. F. C. Souza, André L. Silva, Lucas Amaral-Machado, Éverton N. Alencar, Guilherme M. Chaves and Eryvaldo S. T. Egito
Pharmaceutics 2021, 13(6), 784; https://doi.org/10.3390/pharmaceutics13060784 - 24 May 2021
Cited by 8 | Viewed by 4506
Abstract
Onychomycosis induced by Candida spp. has several limitations regarding its treatment. Nail lacquers display the potential to overcome these drawbacks by providing therapeutic compliance and increasing local drug bioavailability. Thus, this work aimed to produce a nail lacquer loaded with Amphotericin B (AmB) [...] Read more.
Onychomycosis induced by Candida spp. has several limitations regarding its treatment. Nail lacquers display the potential to overcome these drawbacks by providing therapeutic compliance and increasing local drug bioavailability. Thus, this work aimed to produce a nail lacquer loaded with Amphotericin B (AmB) and evaluate its performance. The AmB-loaded nail lacquer was produced and preliminarily characterized. An AmB quantification method was developed. Stability, drug release, permeability and anti-Candida activity assays were conducted. The analytical method validation met the acceptance criteria. The drug loading efficiency was 100% (0.02 mg/g of total product), whereas the AmB stability was limited to ≅7 days (≅90% remaining). The nail lacquer displayed a drying time of 187 s, non-volatile content of around 20%w/w, water-resistance of approximately 2%w/w of weight loss and satisfactory in vitro adhesion. Moreover, the in vitro antifungal activity against different Candida spp. strains was confirmed. The AmB release and the ex vivo permeability studies revealed that AmB leaves the lacquer and permeates the nail matrix in 47.76 ± 0.07% over 24 h. In conclusion, AmB-loaded nail lacquer shows itself as a promising extemporaneous dosage form with remarkable anti-Candida activity related to onychomycosis. Full article
(This article belongs to the Special Issue Antifungal and Antiparasitic Drug Delivery Volume II)
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22 pages, 4973 KiB  
Article
Fluconazole and Lipopeptide Surfactin Interplay During Candida albicans Plasma Membrane and Cell Wall Remodeling Increases Fungal Immune System Exposure
by Jakub Suchodolski, Daria Derkacz, Jakub Muraszko, Jarosław J. Panek, Aneta Jezierska, Marcin Łukaszewicz and Anna Krasowska
Pharmaceutics 2020, 12(4), 314; https://doi.org/10.3390/pharmaceutics12040314 - 1 Apr 2020
Cited by 25 | Viewed by 3768
Abstract
Recognizing the β-glucan component of the Candida albicans cell wall is a necessary step involved in host immune system recognition. Compounds that result in exposed β-glucan recognizable to the immune system could be valuable antifungal drugs. Antifungal development is especially important [...] Read more.
Recognizing the β-glucan component of the Candida albicans cell wall is a necessary step involved in host immune system recognition. Compounds that result in exposed β-glucan recognizable to the immune system could be valuable antifungal drugs. Antifungal development is especially important because fungi are becoming increasingly drug resistant. This study demonstrates that lipopeptide, surfactin, unmasks β-glucan when the C. albicans cells lack ergosterol. This observation also holds when ergosterol is depleted by fluconazole. Surfactin does not enhance the effects of local chitin accumulation in the presence of fluconazole. Expression of the CHS3 gene, encoding a gene product resulting in 80% of cellular chitin, is downregulated. C. albicans exposure to fluconazole changes the composition and structure of the fungal plasma membrane. At the same time, the fungal cell wall is altered and remodeled in a way that makes the fungi susceptible to surfactin. In silico studies show that surfactin can form a complex with β-glucan. Surfactin forms a less stable complex with chitin, which in combination with lowering chitin synthesis, could be a second anti-fungal mechanism of action of this lipopeptide. Full article
(This article belongs to the Special Issue Antifungal and Antiparasitic Drug Delivery Volume II)
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14 pages, 4078 KiB  
Article
Optimization of Drug Permeation from 8% Ciclopirox Cyclodextrin/Poloxamer-Soluble Polypseudorotaxane-Based Nail Lacquers
by Elena Cutrín-Gómez, Andrea Conde-Penedo, Soledad Anguiano-Igea, José Luis Gómez-Amoza and Francisco J. Otero-Espinar
Pharmaceutics 2020, 12(3), 231; https://doi.org/10.3390/pharmaceutics12030231 - 5 Mar 2020
Cited by 10 | Viewed by 3651
Abstract
Cyclodextrin/poloxamer-soluble polypseudorotaxane-based nail lacquers have demonstrated significant capacity for promoting the permeation of drugs into the nail plate. Furthermore, previous studies have shown that the use of hydroalcoholic blends as vehicles promotes drug permeation. The work described herein studies the effect of the [...] Read more.
Cyclodextrin/poloxamer-soluble polypseudorotaxane-based nail lacquers have demonstrated significant capacity for promoting the permeation of drugs into the nail plate. Furthermore, previous studies have shown that the use of hydroalcoholic blends as vehicles promotes drug permeation. The work described herein studies the effect of the type of alcohol used in the lacquer preparation, and the composition of the vehicle is optimized to obtain soluble doses of 8% and to promote the diffusion of ciclopirox base and olamine across the nail. Permeation studies on different types of alcohols show that optimum results are achieved with short-chain alcohols, and that results become less satisfactory the higher the number of alcohol carbons. In addition, solubility and penetration studies on the bovine hoof have enabled the composition of the lacquer to be optimized for both forms of ciclopirox. The results suggest that optimized lacquers have better ciclopirox diffusion and penetration properties than the commercial reference lacquer. Lastly, in vivo studies in which optimized ciclopirox olamine lacquer was applied for 45 days to the nails of healthy volunteers showed that it caused no negative effects or changes to the nail surface. These results demonstrate the significant potential of cyclodextrin/poloxamer-soluble polypseudorotaxane-based nail lacquers for the ungual administration of drugs. Full article
(This article belongs to the Special Issue Antifungal and Antiparasitic Drug Delivery Volume II)
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Review

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47 pages, 835 KiB  
Review
Lipid Systems for the Delivery of Amphotericin B in Antifungal Therapy
by Célia Faustino and Lídia Pinheiro
Pharmaceutics 2020, 12(1), 29; https://doi.org/10.3390/pharmaceutics12010029 - 1 Jan 2020
Cited by 135 | Viewed by 13219
Abstract
Amphotericin B (AmB), a broad-spectrum polyene antibiotic in the clinic for more than fifty years, remains the gold standard in the treatment of life-threatening invasive fungal infections and visceral leishmaniasis. Due to its poor water solubility and membrane permeability, AmB is conventionally formulated [...] Read more.
Amphotericin B (AmB), a broad-spectrum polyene antibiotic in the clinic for more than fifty years, remains the gold standard in the treatment of life-threatening invasive fungal infections and visceral leishmaniasis. Due to its poor water solubility and membrane permeability, AmB is conventionally formulated with deoxycholate as a micellar suspension for intravenous administration, but severe infusion-related side effects and nephrotoxicity hamper its therapeutic potential. Lipid-based formulations, such as liposomal AmB, have been developed which significantly reduce the toxic side effects of the drug. However, their high cost and the need for parenteral administration limit their widespread use. Therefore, delivery systems that can retain or even enhance antimicrobial efficacy while simultaneously reducing AmB adverse events are an active area of research. Among those, lipid systems have been extensively investigated due to the high affinity of AmB for binding lipids. The development of a safe and cost-effective oral formulation able to improve drug accessibility would be a major breakthrough, and several lipid systems for the oral delivery of AmB are currently under development. This review summarizes recent advances in lipid-based systems for targeted delivery of AmB focusing on non-parenteral nanoparticulate formulations mainly investigated over the last five years and highlighting those that are currently in clinical trials. Full article
(This article belongs to the Special Issue Antifungal and Antiparasitic Drug Delivery Volume II)
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