Targeting lung macrophages for fungal and parasitic pulmonary infections with innovative amphotericin B dry powder inhalers

Pablo, Esther de; O’Connell, P.; Fernández-García, Raquel; Marchand, Sandrine; Chauzy, Alexia; Tewes, Frédéric; Dea-Ayuela, M. Auxiliadora; Kumar, Dinesh; Bolás, F; Ballesteros, M.; Torrado, Juan J.; Healy, Anne Marie; Serrano, Dolores R.

doi:10.1016/j.ijpharm.2023.122788

Cited by 16 publications

(18 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thanks to the nano-in-micro system, excellent in vitro aerodynamic performance was recorded, with ~71% FPF and ~2.5 µm MMAD. The in vitro aerosol performance results are considered promising and in line with other studies [78]. The highest lung deposition fractions in the in silico study were found in F0.5 and F1, which are correlated with in vitro results.…”

Section: Discussionsupporting

confidence: 88%

A Novel Combined Dry Powder Inhaler Comprising Nanosized Ketoprofen-Embedded Mannitol-Coated Microparticles for Pulmonary Inflammations: Development, In Vitro–In Silico Characterization, and Cell Line Evaluation

Banat,

Csóka,

Paróczai

et al. 2024

Pharmaceuticals

View full text Add to dashboard Cite

Pulmonary inflammations such as chronic obstructive pulmonary disease and cystic fibrosis are widespread and can be fatal, especially when they are characterized by abnormal mucus accumulation. Inhaled corticosteroids are commonly used for lung inflammations despite their considerable side effects. By utilizing particle engineering techniques, a combined dry powder inhaler (DPI) comprising nanosized ketoprofen-embedded mannitol-coated microparticles was developed. A nanoembedded microparticle system means a novel advance in pulmonary delivery by enhancing local pulmonary deposition while avoiding clearance mechanisms. Ketoprofen, a poorly water-soluble anti-inflammatory drug, was dispersed in the stabilizer solution and then homogenized by ultraturrax. Following this, a ketoprofen-containing nanosuspension was produced by wet-media milling. Furthermore, co-spray drying was conducted with L-leucine (dispersity enhancer) and mannitol (coating and mucuactive agent). Particle size, morphology, dissolution, permeation, viscosity, in vitro and in silico deposition, cytotoxicity, and anti-inflammatory effect were investigated. The particle size of the ketoprofen-containing nanosuspension was ~230 nm. SEM images of the spray-dried powder displayed wrinkled, coated, and nearly spherical particles with a final size of ~2 µm (nano-in-micro), which is optimal for pulmonary delivery. The mannitol-containing samples decreased the viscosity of 10% mucin solution. The results of the mass median aerodynamic diameter (2.4–4.5 µm), fine particle fraction (56–71%), permeation (five-fold enhancement), and dissolution (80% release in 5 min) confirmed that the system is ideal for local inhalation. All samples showed a significant anti-inflammatory effect and decreased IL-6 on the LPS-treated U937 cell line with low cytotoxicity. Hence, developing an innovative combined DPI comprising ketoprofen and mannitol by employing a nano-in-micro approach is a potential treatment for lung inflammations.

show abstract

Section: Discussionsupporting

confidence: 88%

A Novel Combined Dry Powder Inhaler Comprising Nanosized Ketoprofen-Embedded Mannitol-Coated Microparticles for Pulmonary Inflammations: Development, In Vitro–In Silico Characterization, and Cell Line Evaluation

Banat,

Csóka,

Paróczai

et al. 2024

Pharmaceuticals

View full text Add to dashboard Cite

show abstract

“…Inhalable and spray-dried microparticles of TRB 45,46 have been studied for the treatment of pulmonary fungal infections to enhance the beneficial effects of antifungal drugs as well as AmB. 47 TRB, which does not require particularly prolonged exposure (Fig. 4), would be a suitable inhaled drug for the treatment of E. dermatitidis pneumonia, which has been reported in approximately 6 % of patients with bronchiectasis and cystic fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Antifungal potency of terbinafine as a therapeutic agent against Exophiala dermatitidis in vitro

Nakamura,

Yoshinouchi,

Okumura

et al. 2024

Preprint

View full text Add to dashboard Cite

Background: Exophiala dermatitidis (E. dermatitidis), which causes skin infections or respiratory diseases, is occasionally fatal in immunocompromised patients. Objectives: Here, we report the unique antifungal potency of terbinafine (TRB), which targets squalene epoxidase, against E. dermatitidis (SQLEED) using various in vitro approaches. Methods: Based on the human SQLE crystal structure, we created a structure model of SQLEED using SWISS-MODEL and determined the best-fitting model of TRB to the SQLEED. The versatile antifungal activities, including fungicidal activity, biofilm inhibition, biofilm eradication activity, and the combination effect of TRB, posaconazole (PSC), and amphotericin B (AmB) with great antifungal potency against E. dermatitidis were evaluated using crystal violet and cell viability assay. Results: Clinically isolated E. dermatitidis increased most vigorously at 30°C but decreased at 40°C. E. dermatitidis hyphae elongated and attached to a cell scaffold, forming a membrane-like biofilm that was distinct from the cell-free biofilm. In the binding model, TRB formed an H-bond with Y102 and was surrounded by key amino acid residues of SQLEED corresponding to TRB-resistant mutations in Trichophyton rubrum, showing an appropriate interaction. Among TRB, PSC, and AmB with potent antifungal activities, TRB and PSC showed more potent antibiofilm activities than AmB. In addition, TRB and PSC exhibited residual potency without incubation against E. dermatitidis, decreasing the growth at lower concentrations than AmB. In contrast, AmB exhibited strong time-dependent killing and eradication activities. The combination of TRB and PSC was more effective than that of TRB and AmB or PSC and AmB in vitro. Conclusions: Although the tissue migration of TRB must be considered, these data suggest that TRB and PSC may be useful agents and a potent combination in severely immunocompromised patients with refractory and systemic E. dermatitidis infection.

show abstract

“…Nebulization is the method that converts medications into fine mist for inhalation, which has shown promise in enhancing the delivery of amphotericin B and combating pulmonary fungal infections. Apart from the nebulization, pressurized metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs) are also being used for drug delivery, but each device requires different formulations to ensure successful drug delivery into the lung [ 165 , 166 , 167 ].…”

Section: Pharmaceutical Applications Of Liposomesmentioning

confidence: 99%

Lipid-Based Nanotechnology: Liposome

Jiang,

Li,

Wang

et al. 2023

Pharmaceutics

View full text Add to dashboard Cite

Over the past several decades, liposomes have been extensively developed and used for various clinical applications such as in pharmaceutical, cosmetic, and dietetic fields, due to its versatility, biocompatibility, and biodegradability, as well as the ability to enhance the therapeutic index of free drugs. However, some challenges remain unsolved, including liposome premature leakage, manufacturing irreproducibility, and limited translation success. This article reviews various aspects of liposomes, including its advantages, major compositions, and common preparation techniques, and discusses present U.S. FDA-approved, clinical, and preclinical liposomal nanotherapeutics for treating and preventing a variety of human diseases. In addition, we summarize the significance of and challenges in liposome-enabled nanotherapeutic development and hope it provides the fundamental knowledge and concepts about liposomes and their applications and contributions in contemporary pharmaceutical advancement.

show abstract

Targeting lung macrophages for fungal and parasitic pulmonary infections with innovative amphotericin B dry powder inhalers

Cited by 16 publications

References 60 publications

A Novel Combined Dry Powder Inhaler Comprising Nanosized Ketoprofen-Embedded Mannitol-Coated Microparticles for Pulmonary Inflammations: Development, In Vitro–In Silico Characterization, and Cell Line Evaluation

A Novel Combined Dry Powder Inhaler Comprising Nanosized Ketoprofen-Embedded Mannitol-Coated Microparticles for Pulmonary Inflammations: Development, In Vitro–In Silico Characterization, and Cell Line Evaluation

Antifungal potency of terbinafine as a therapeutic agent against Exophiala dermatitidis in vitro

Lipid-Based Nanotechnology: Liposome

Contact Info

Product

Resources

About