Antifungal and Antiparasitic Drug Delivery

A special issue of Pharmaceutics (ISSN 1999-4923).

Deadline for manuscript submissions: closed (11 October 2019) | Viewed by 42636

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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
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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
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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
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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 J. Torrado
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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Published Papers (11 papers)

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Editorial

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4 pages, 194 KiB  
Editorial
Antifungal and Antiparasitic Drug Delivery
by Juan José Torrado, Dolores R. Serrano and Javier Capilla
Pharmaceutics 2020, 12(4), 324; https://doi.org/10.3390/pharmaceutics12040324 - 04 Apr 2020
Cited by 1 | Viewed by 2357
Abstract
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. [...] Read more.
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. This Editorial regards the ten research contributions presented in the Special Issue “Antifungal and Antiparasitic Drug Delivery”. Full article
(This article belongs to the Special Issue Antifungal and Antiparasitic Drug Delivery)

Research

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20 pages, 2809 KiB  
Article
Development of Amphotericin B Micellar Formulations Based on Copolymers of Poly(ethylene glycol) and Poly(ε-caprolactone) Conjugated with Retinol
by Yeimy J. Rodriguez, Luis F. Quejada, Jean C. Villamil, Yolima Baena, Claudia M. Parra-Giraldo and Leon D. Perez
Pharmaceutics 2020, 12(3), 196; https://doi.org/10.3390/pharmaceutics12030196 - 25 Feb 2020
Cited by 17 | Viewed by 3558
Abstract
Amphotericin B (AmB) is a broad spectrum of antifungal drug used to treat antifungal diseases. However, due to the high toxicity of AmB, treated patients may suffer the risk of side effects, such as renal failure. Nanoencapsulation strategies have been reported to elicit [...] Read more.
Amphotericin B (AmB) is a broad spectrum of antifungal drug used to treat antifungal diseases. However, due to the high toxicity of AmB, treated patients may suffer the risk of side effects, such as renal failure. Nanoencapsulation strategies have been reported to elicit low toxicity, albeit most of them possess low encapsulation efficiency. The aim of this research is to develop micellar delivery systems for AmB with reduced toxicity while maintaining its affectivity by employing retinol (RET)-conjugated amphiphilic block copolymers (ABCs) as precursors. Copolymers composed of poly(ε-caprolactone) (A) and polyethylenglycol (B) of types AB and ABA were synthesized by ring opening polymerization and subsequently conjugated with RET by Steglich esterification. 1H-NMR spectroscopy was used to corroborate the structure of copolymers and their conjugates and determine their molecular weights. Analysis by gel permeation chromatography also found that the materials have narrow distributions. The resulting copolymers were used as precursors for delivery systems of AmB, thus reducing its aggregation and consequently causing a low haemolytic effect. Upon conjugation with RET, the encapsulation capacity was enhanced from approximately 2 wt % for AB and ABA copolymers to 10 wt %. AmB encapsulated in polymer micelles presented improved antifungal efficiency against Candida albicans and Candida auris strains compared with Fungizone®, as deduced from the low minimum inhibitory concentration. Full article
(This article belongs to the Special Issue Antifungal and Antiparasitic Drug Delivery)
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16 pages, 2449 KiB  
Article
Development and Characterization of a Semi-Solid Dosage Form of Meglumine Antimoniate for Topical Treatment of Cutaneous Leishmaniasis
by Diana Berenguer, Lilian Sosa, Magdalena Alcover, Marcella Sessa, Lyda Halbaut, Carme Guillén, Roser Fisa, Ana Cristina Calpena-Campmany and Cristina Riera
Pharmaceutics 2019, 11(11), 613; https://doi.org/10.3390/pharmaceutics11110613 - 15 Nov 2019
Cited by 12 | Viewed by 3481
Abstract
Cutaneous leishmaniasis (CL) is treated with painful intralesional injections of meglumine antimoniate (MA). With the aim of developing an alternative topical treatment for CL, a gel-based formulation with 30% MA was prepared and its physicochemical properties, stability and rheological behavior were studied. The [...] Read more.
Cutaneous leishmaniasis (CL) is treated with painful intralesional injections of meglumine antimoniate (MA). With the aim of developing an alternative topical treatment for CL, a gel-based formulation with 30% MA was prepared and its physicochemical properties, stability and rheological behavior were studied. The following were assessed: drug release on propylene hydrophilic membranes ex vivo human skin permeation, tolerance in healthy volunteers, cytotoxicity in three cell lines and anti-leishmanial activity against Leishmania infantum promastigotes and amastigotes. The MA gel formulation was found to have suitable pH, and good spreadability and stability. Low quantities of pentavalent antimony (SbV) were observed in release and permeation tests, whereas retention was high in both non-damaged and damaged skin (71,043.69 ± 10,641.57 and 10,728 ± 2254.61 µg/g/cm2 of SbV, respectively). The formulation did not have a toxic effect on the cell lines, and presented lower SbV IC50 values against amastigotes (15.76 ± 4.81 µg/mL) in comparison with the MA solution. The high amount of drug retained in the skin and the SbV IC50 values obtained suggest that this semi-solid dosage form has potential as an alternative treatment of CL. Full article
(This article belongs to the Special Issue Antifungal and Antiparasitic Drug Delivery)
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12 pages, 5417 KiB  
Article
Resorbable Beads Provide Extended Release of Antifungal Medication: In Vitro and In Vivo Analyses
by Yung-Heng Hsu, Huang-Yu Chen, Jin-Chung Chen, Yi-Hsun Yu, Ying-Chao Chou, Steve Wen-Neng Ueng and Shih-Jung Liu
Pharmaceutics 2019, 11(11), 550; https://doi.org/10.3390/pharmaceutics11110550 - 24 Oct 2019
Cited by 4 | Viewed by 3069
Abstract
Fungal osteomyelitis has been difficult to treat, with first-line treatments consisting of implant excision, radical debridement, and local release of high-dose antifungal agents. Locally impregnated antifungal beads are another popular treatment option. This study aimed to develop biodegradable antifungal-agent-loaded Poly(d,l [...] Read more.
Fungal osteomyelitis has been difficult to treat, with first-line treatments consisting of implant excision, radical debridement, and local release of high-dose antifungal agents. Locally impregnated antifungal beads are another popular treatment option. This study aimed to develop biodegradable antifungal-agent-loaded Poly(d,l-lactide-co-glycolide) (PLGA) beads and evaluate the in vitro/in vivo release patterns of amphotericin B and fluconazole from the beads. Beads of different sizes were formed using a compression-molding method, and their morphology was evaluated via scanning electron microscopy. Intrabead incorporation of antifungal agents was evaluated via Fourier-transform infrared spectroscopy, and in vitro fluconazole liberation curves of PLGA beads were inspected via high-performance liquid chromatography. When we implanted the drug-incorporated beads into the bone cavity of rabbits, we found that a high level of fluconazole (beyond the minimum therapeutic concentration [MTC]) was released for more than 49 d in vivo. Our results indicate that compression-molded PLGA/fluconazole beads have potential applications in treating bone infections. Full article
(This article belongs to the Special Issue Antifungal and Antiparasitic Drug Delivery)
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12 pages, 1262 KiB  
Article
Ground Calcium Carbonate as a Low Cost and Biosafety Excipient for Solubility and Dissolution Improvement of Praziquantel
by Ana Borrego-Sánchez, Rita Sánchez-Espejo, Beatrice Albertini, Nadia Passerini, Pilar Cerezo, César Viseras and C. Ignacio Sainz-Díaz
Pharmaceutics 2019, 11(10), 533; https://doi.org/10.3390/pharmaceutics11100533 - 14 Oct 2019
Cited by 16 | Viewed by 5703
Abstract
Calcium carbonate is an abundant mineral with several advantages to be a successful carrier to improve oral bioavailability of poorly water-soluble drugs, such as praziquantel. Praziquantel is an antiparasitic drug classified in group II of the Biopharmaceutical Classification System hence characterized by high-permeability [...] Read more.
Calcium carbonate is an abundant mineral with several advantages to be a successful carrier to improve oral bioavailability of poorly water-soluble drugs, such as praziquantel. Praziquantel is an antiparasitic drug classified in group II of the Biopharmaceutical Classification System hence characterized by high-permeability and low-solubility. Therefore, the dissolution rate is the limiting factor for the gastrointestinal absorption that contributes to the low bioavailability. Consequently, the therapeutic dose of the praziquantel must be high and big tablets and capsules are required, which are difficult to swallow, especially for pediatric and elderly patients. Mixtures of praziquantel and calcium carbonate using solid-solid physical mixtures and solid dispersions were prepared and characterized using several techniques (X-ray diffraction differential scanning calorimetry, thermogravimetric analysis, scanning electron microscopy, laser diffraction, Fourier transform infrared and Raman spectroscopies). Solubility of these formulations evidenced that the solubility of praziquantel-calcium carbonate interaction product increased in physiological media. In vitro dissolution tests showed that the interaction product increased the dissolution rate of the drug in acidic medium. Theoretical models were studied to understand this experimental behavior. Cytotoxicity and cell cycle studies were performed, showing that praziquantel-calcium carbonate physical mixture and interaction product were biocompatible with the HTC116 cells, because it did not produce a decrease in cell viability or alterations in the cell cycle. Full article
(This article belongs to the Special Issue Antifungal and Antiparasitic Drug Delivery)
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13 pages, 2421 KiB  
Article
Increased Efficacy of Oral Fixed-Dose Combination of Amphotericin B and AHCC® Natural Adjuvant against Aspergillosis
by Alba Pérez-Cantero, Dolores R. Serrano, Patricia Navarro-Rodríguez, Andreas G. Schätzlein, Ijeoma F. Uchegbu, Juan J. Torrado and Javier Capilla
Pharmaceutics 2019, 11(9), 456; https://doi.org/10.3390/pharmaceutics11090456 - 03 Sep 2019
Cited by 8 | Viewed by 3212
Abstract
Invasive pulmonary aspergillosis represents one of the most serious fungal infections among immunocompromised patients. In this study, we aimed to analyze the in vivo efficacy of prophylactic oral amphotericin B (AMB) encapsulated in modified chitosan-nanoparticles (Nanomerics’ Molecular Envelope Technology (MET)) supplemented with a [...] Read more.
Invasive pulmonary aspergillosis represents one of the most serious fungal infections among immunocompromised patients. In this study, we aimed to analyze the in vivo efficacy of prophylactic oral amphotericin B (AMB) encapsulated in modified chitosan-nanoparticles (Nanomerics’ Molecular Envelope Technology (MET)) supplemented with a standardized extract of cultured Lentinula edodes mycelia (AHCC®) in a murine model of pulmonary aspergillosis. We determined fungal burden and survival of mice and additionally, we carried out a cytokine analysis in an attempt to understand the immunomodulation of the extract. Our results evidenced equivalent efficacy between orally administered AMB-MET and the intravenous liposomal AMB marketed formulation. Addition of the AHCC® supplement significantly improved efficacy in terms of burden reduction and survival increase of both oral and intravenous AMB therapies compared to the untreated control group. Moreover, a protective effect of the extract was observed in terms of weight loss. Regarding the cytokine profiles, the Th1 immune response was stimulated in treated animals when compared to the control group. This response was marked by an enhancement in the MCP-1, GM-CSF, VEGF, RANTES and IL-17 levels and a decrease in the IL-6, a biomarker related to the severity of the infection. Full article
(This article belongs to the Special Issue Antifungal and Antiparasitic Drug Delivery)
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16 pages, 3719 KiB  
Article
Designing Fast-Dissolving Orodispersible Films of Amphotericin B for Oropharyngeal Candidiasis
by Dolores R. Serrano, Raquel Fernandez-Garcia, Marta Mele, Anne Marie Healy and Aikaterini Lalatsa
Pharmaceutics 2019, 11(8), 369; https://doi.org/10.3390/pharmaceutics11080369 - 01 Aug 2019
Cited by 37 | Viewed by 4956
Abstract
Amphotericin B possesses high activity against Candida spp. with low risk of resistance. However, Amphotericin B’s high molecular weight compared to other antifungal drugs, such as miconazole and clotrimazole, and poor water solubility hampers its efficacy at the physiological conditions of the oropharyngeal [...] Read more.
Amphotericin B possesses high activity against Candida spp. with low risk of resistance. However, Amphotericin B’s high molecular weight compared to other antifungal drugs, such as miconazole and clotrimazole, and poor water solubility hampers its efficacy at the physiological conditions of the oropharyngeal cavity (saliva pH, limited volume for dissolution) and thereby limits its clinical use in oropharyngeal candidiasis. We have prepared fast-dissolving orodispersible films with high loading (1% w/w) using solvent casting that enables amphotericin B to remain solubilised in saliva in equilibrium between the monomeric and dimeric states, and able to produce a local antifungal effect. Optimisation of the amphotericin B-loaded orodispersible films was achieved by quality by design studies combining dextran and/or maltodextrin as dextrose-derived-polymer film formers with cellulose-derived film formers (hydroxypropylmethyl/hydroxypropyl cellulose in a 1:4 weight ratio), sorbitol for taste masking, microcrystalline cellulose (Avicel 200) or microcrystalline cellulose-carboxymethylcellulose sodium (Avicel CL-611) for enhancing the mechanical strength of the film, and polyethylene glycol 400 and glycerol (1:1 w/w) as plasticizers. The optimised amphotericin B orodispersible films (containing 1% AmB, 25% dextran, 25% maltodextrin, 5% sorbitol, 10% Avicel 200, 10% polyethylene glycol 400, 10% glycerol, 3% hydroxypropylmethyl cellulose acetate succinate, 12% hydroxypropyl cellulose) possessed a fast disintegration time (60 ± 3 s), quick release in artificial saliva (>80% in 10 min), high burst strength (2190 mN mm) and high efficacy against several Candida spp. (C. albicans, C. parapsilosis and C. krusei) (>15 mm inhibition halo). Amphotericin B orodispersible films are stable for two weeks at room temperature (25 °C) and up to 1 year in the fridge. Although further toxicological and in vivo efficacy studies are required, this novel Amphotericin B orodispersible films is a promising, physicochemically stable formulation with potential wide application in clinical practice, especially for immunocompromised patients suffering from oropharyngeal candidiasis. Full article
(This article belongs to the Special Issue Antifungal and Antiparasitic Drug Delivery)
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14 pages, 1756 KiB  
Article
Repurposing Butenafine as An Oral Nanomedicine for Visceral Leishmaniasis
by Adriana Bezerra-Souza, Raquel Fernandez-Garcia, Gabriela F. Rodrigues, Francisco Bolas-Fernandez, Marcia Dalastra Laurenti, Luiz Felipe Passero, Aikaterini Lalatsa and Dolores R. Serrano
Pharmaceutics 2019, 11(7), 353; https://doi.org/10.3390/pharmaceutics11070353 - 20 Jul 2019
Cited by 16 | Viewed by 4483
Abstract
Leishmaniasis is a neglected tropical disease affecting more than 12 million people worldwide, which in its visceral clinical form (VL) is characterised by the accumulation of parasites in the liver and spleen, and can lead to death if not treated. Available treatments are [...] Read more.
Leishmaniasis is a neglected tropical disease affecting more than 12 million people worldwide, which in its visceral clinical form (VL) is characterised by the accumulation of parasites in the liver and spleen, and can lead to death if not treated. Available treatments are not well tolerated due to severe adverse effects, need for parenteral administration and patient hospitalisation, and long duration of expensive treatments. These treatment realities justify the search for new effective drugs, repurposing existing licensed drugs towards safer and non-invasive cost-effective medicines for VL. In this work, we provide proof of concept studies of butenafine and butenafine self-nanoemulsifying drug delivery systems (B-SNEDDS) against Leishmania infantum. Liquid B-SNEDDS were optimised using design of experiments, and then were spray-dried onto porous colloidal silica carriers to produce solid-B-SNEDDS with enhanced flow properties and drug stability. Optimal liquid B-SNEDDS consisted of Butenafine:Capryol 90:Peceol:Labrasol (3:49.5:24.2:23.3 w/w), which were then sprayed-dried with Aerosil 200 with a final 1:2 (Aerosil:liquid B-SNEDDS w/w) ratio. Spray-dried particles exhibited near-maximal drug loading, while maintaining excellent powder flow properties (angle of repose <10°) and sustained release in acidic gastrointestinal media. Solid-B-SNEDDS demonstrated greater selectivity index against promastigotes and L. infantum-infected amastigotes than butenafine alone. Developed oral solid nanomedicines enable the non-invasive and safe administration of butenafine as a cost-effective and readily scalable repurposed medicine for VL. Full article
(This article belongs to the Special Issue Antifungal and Antiparasitic Drug Delivery)
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18 pages, 5172 KiB  
Article
Thermoreversible Gel-Loaded Amphotericin B for the Treatment of Dermal and Vaginal Candidiasis
by Lilian Sosa, Ana Cristina Calpena, Marcelle Silva-Abreu, Lupe Carolina Espinoza, María Rincón, Nuria Bozal, Oscar Domenech, María José Rodríguez-Lagunas and Beatriz Clares
Pharmaceutics 2019, 11(7), 312; https://doi.org/10.3390/pharmaceutics11070312 - 03 Jul 2019
Cited by 30 | Viewed by 3572
Abstract
The present study was designed to develop a thermoreversible gel of Pluronic (P407) loaded amphotericin B (AmB-gel) for the dermal and vaginal treatment of candidiasis. P407 was used as a copolymer to exploit potential advantages related to increasing drug concentration in the tissue [...] Read more.
The present study was designed to develop a thermoreversible gel of Pluronic (P407) loaded amphotericin B (AmB-gel) for the dermal and vaginal treatment of candidiasis. P407 was used as a copolymer to exploit potential advantages related to increasing drug concentration in the tissue layer in order to provide a local effect. Parameters including internal structure, swelling, porosity, and short-term stability were determined. In addition, drug release profile and ex vivo skin and vaginal permeation studies were carried out. Antifungal efficacy was evaluated against strains of Candida spp. and atomic force microscopy (AFM) supported the results. The tolerance of AmB-gel was studied by evaluating biomechanical properties of skin and determining the irritation level in scarified rabbit skin supported by histological analysis. Results confirmed the development of a thermoreversible AmB-gel with high porosity exhibiting Newtonian behavior at 4 °C and pseudoplasticity at 32 °C as well as optimal stability for at least 90 days. The Amb-gel provided a sustained drug release following a Boltzmann sigmoidal model. Non permeation was observed in skin and vaginal mucosa, showing a high retained amount of AmB of 960.0 and 737.3 µg/g/cm2, respectively. In vitro antifungal efficacy showed that AmB-gel was more effective than Free-AmB in inhibiting strains of Candida spp. and these results were corroborated by AFM. Finally, tolerance studies showed that its application did not induce skin irritation nor alter its biophysical properties. Together, these results confirmed that AmB-gel could be proposed as a promising candidate for the clinical status in the treatment of skin and vaginal candidiasis. Full article
(This article belongs to the Special Issue Antifungal and Antiparasitic Drug Delivery)
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18 pages, 2211 KiB  
Article
A Functional Wound Dressing as a Potential Treatment for Cutaneous Leishmaniasis
by Francisco Alexandrino-Junior, Kattya Gyselle de Holanda e Silva, Marjorie Caroline Liberato Cavalcanti Freire, Viviane de Oliveira Freitas Lione, Elisama Azevedo Cardoso, Henrique Rodrigues Marcelino, Julieta Genre, Anselmo Gomes de Oliveira and Eryvaldo Sócrates Tabosa do Egito
Pharmaceutics 2019, 11(5), 200; https://doi.org/10.3390/pharmaceutics11050200 - 01 May 2019
Cited by 15 | Viewed by 3908
Abstract
Cutaneous leishmaniasis (CL) is a parasitic disease characterized by progressive skin sores. Currently, treatments for CL are limited to parenteral administration of the drug, which presents severe adverse effects and low cure rates. Therefore, this study aimed to develop poly(vinyl-alcohol) (PVA) hydrogels containing [...] Read more.
Cutaneous leishmaniasis (CL) is a parasitic disease characterized by progressive skin sores. Currently, treatments for CL are limited to parenteral administration of the drug, which presents severe adverse effects and low cure rates. Therefore, this study aimed to develop poly(vinyl-alcohol) (PVA) hydrogels containing Amphotericin B (AmB) intended for topical treatment of CL. Hydrogels were evaluated in vitro for their potential to eliminate promastigote forms of Leishmania spp., to prevent secondary infections, to maintain appropriate healing conditions, and to offer suitable biocompatibility. AmB was incorporated into the system in its non-crystalline state, allowing it to swell more and faster than the system without the drug. Furthermore, the AmB release profile showed a continuous and controlled behavior following Higuchi´s kinetic model. AmB-loaded-PVA-hydrogels (PVA–AmB) also showed efficient antifungal and leishmanicidal activity, no cytotoxic potential for VERO cells, microbial impermeability and water vapor permeability compatible with the healthy skin’s physiological needs. Indeed, these results revealed the potential of PVA–AmB to prevent secondary infections and to maintain a favorable environment for the healing process. Hence, these results suggest that PVA–AmB could be a suitable and efficient new therapeutic approach for the topical treatment of CL. Full article
(This article belongs to the Special Issue Antifungal and Antiparasitic Drug Delivery)
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13 pages, 2033 KiB  
Article
A Recombinant Enolase-Montanide™ PetGel A Vaccine Promotes a Protective Th1 Immune Response against a Highly Virulent Sporothrix schenckii by Toluene Exposure
by Damiana Téllez-Martínez, Deivys Leandro Portuondo, Maria Luiza Loesch, Alexander Batista-Duharte and Iracilda Zeppone Carlos
Pharmaceutics 2019, 11(3), 144; https://doi.org/10.3390/pharmaceutics11030144 - 25 Mar 2019
Cited by 13 | Viewed by 3414
Abstract
The effect of vaccination in fungal strains that suffered changes in their virulence by exposure to environmental contaminants is largely known. Growing reports of resistance to antifungal drugs and the emergence of new highly virulent strains, possibly acquired in the environment, prompt the [...] Read more.
The effect of vaccination in fungal strains that suffered changes in their virulence by exposure to environmental contaminants is largely known. Growing reports of resistance to antifungal drugs and the emergence of new highly virulent strains, possibly acquired in the environment, prompt the design of new vaccines able to prevent and combat emerging mycotic diseases. In this study, we evaluated the protective capacity of an enolase-based vaccine and Montanide PetGel A (PGA) as an adjuvant against S. schenckii with increased virulence by exposure to toluene. The adjuvanted vaccine induced a strong specific Th1 response and protective immunity against a challenge with either wildtype or toluene-adapted S. schenckii in Balb/c mice. This study highlights the role of the adjuvant PGA driving the quality of the anti-sporothrix immunity and the key component in the vaccine efficacy. Full article
(This article belongs to the Special Issue Antifungal and Antiparasitic Drug Delivery)
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