Antifungal efficacy and immunomodulatory effect of PLGA nanoparticle-encapsulated itraconazole in histoplasmosis in vivo model.

Introduction: Histoplasma capsulatum is the etiological agent of histoplasmosis, the most common endemic pulmonary mycosis. Itraconazole (ITZ) is the choice for mild disease and a step-down therapy in severe and disseminated clinical presentations. Drug encapsulation into nanoparticles (NPs) is an alternative to improve drug solubility and bioavailability, reducing undesirable interactions and drug degradation and reaching the specific therapeutic target with lower doses.

Effect of Protein Corona on the Specificity and Efficacy of Nanobioconjugates to Treat Intracellular Infections.

Encapsulating drugs into functionalized nanoparticles (NPs) is an alternative to reach the specific therapeutic target with lower doses. However, when the NPs are in contact with physiological media, proteins adsorb on their surfaces, forming a protein corona (PC) biomolecular layer, acquiring a distinct biological identity that alters their interactions with cells. Itraconazole (ITZ), an antifungal agent, is encapsulated into PEGylated and/or functionalized NPs with high specificity for macrophages.

Antifungal Encapsulated into Ligand-Functionalized Nanoparticles with High Specificity for Macrophages.

Infectious diseases caused by intracellular microorganisms such as represent a significant challenge worldwide. Drug encapsulation into functionalized nanoparticles (NPs) is a valuable alternative to improving drug solubility and bioavailability, preventing undesirable interactions and drug degradation, and reaching the specific therapeutic target with lower doses. This work reports on Itraconazole (ITZ) encapsulated into core-shell-like polymeric NPs and functionalized with anti-F4/80 antibodies for their targeted and controlled release into macrophages.

Functional Nanocarriers for Delivering Itraconazole Against Fungal Intracellular Infections.

Infectious diseases caused by intracellular microorganisms represent a significant challenge in medical care due to interactions among drugs during coinfections and the development of resistance in microorganisms, limiting existing therapies. This work reports on itraconazole (ITZ) encapsulated into functional polymeric nanoparticles for their targeted and controlled release into macrophages to fight intracellular infections. NPs are based on poly (lactic acid-co-glycolic acid) (PLGA) polymers of different compositions, molecular weights, and lactic acid-to-glycolic acid ratios.

The Role of the Interleukin-17 Axis and Neutrophils in the Pathogenesis of Endemic and Systemic Mycoses.

Systemic and endemic mycoses are considered life-threatening respiratory diseases which are caused by a group of dimorphic fungal pathogens belonging to the genera , , , , , and the newly described pathogen . T-cell mediated immunity, mainly T helper (Th)1 and Th17 responses, are essential for protection against these dimorphic fungi; thus, IL-17 production is associated with neutrophil and macrophage recruitment at the site of infection accompanied by chemokines and proinflammatory cytokines production, a mechanism that is mediated by some pattern recognition receptors (PRRs), including Dectin-1, Dectine-2, TLRs, Mannose receptor (MR), Galectin-3 and NLPR3, and the adaptor molecules caspase adaptor recruitment domain family member 9 (Card9), and myeloid differentiation factor 88 (MyD88). However, these PRRs play distinctly different roles for each pathogen.

Recent Advances in Polymeric Nanoparticle-Encapsulated Drugs against Intracellular Infections.

Polymeric nanocarriers (PNs) have demonstrated to be a promising alternative to treat intracellular infections. They have outstanding performance in delivering antimicrobials intracellularly to reach an adequate dose level and improve their therapeutic efficacy. PNs offer opportunities for preventing unwanted drug interactions and degradation before reaching the target cell of tissue and thus decreasing the development of resistance in microorganisms.

Human neutrophils produce extracellular traps against Paracoccidioides brasiliensis.

Neutrophils play an important role as effector cells and contribute to the resistance of the host against microbial pathogens. Neutrophils are able to produce extracellular traps (NETs) in response to medically important fungi, including Aspergillus spp., Candida albicans and Cryptococcus gattii.