Abstract
Pulmonary aspergillosis (PA), a pulmonary fungal infection caused by Aspergillus spp., is a concern for immunocompromised populations. Despite substantial research efforts, conventional treatments of PA using antifungal agents are associated with limitations such as excessive systemic exposure, serious side effects and limited availability of the therapeutics in the lungs for an adequate duration. To overcome the limitations associated with the conventional regimens, pulmonary delivery of antifungal agents has become a focal point of research because of the superiority of local and targeted drug delivery. Dry powder inhalers and nebulized formulations of antifungal agents have been developed and evaluated for their capability to effectively deliver antifungal agents to the lungs. Moreover, progress in nanotechnology and the utilization of nanocarriers in the development of pulmonary delivery formulations has allowed further augmentation of treatment capability and efficiency. Thus, the following review provides an insight into the advantages and therapeutic potential of the utilization of nanocarriers in pulmonary delivery of antifungal agents for the treatment of PA. In addition, discussions on formulation aspects and safety concerns together with the clinical and regulatory aspects of the formulations are presented, which suggest the possibility and desirability of utilization of nanocarriers in the treatment of PA.
Highlights
Lungs are one of the most common sites that can be infected by a variety of microorganisms such as bacteria, viruses, parasites and fungi
To assess the biodistribution of Nano-D-amphotericin B (AmB), 99mTc was used to label the nanoparticles and the results showed that high concentrations of Nano-desoxycholate AMB (D-AmB) accumulated in lungs, liver and spleen following IV route of administration than the 99mTc-dimercaptosuccinic acid (DMSA)
The PEG-lipid nanoparticles (LN) AmB formulation showed less cytotoxicity in a human kidney cell line than the commercially available formulations, Fungizone® and AmBisome®. This was due to the slower release of drug from the stronger barrier provided by the lipid matrix of LN, which suggested that the LN formulation of AmB could reduce the nephrotoxicity more effectively
Summary
Lungs are one of the most common sites that can be infected by a variety of microorganisms such as bacteria, viruses, parasites and fungi. Among the types of lung infections, pneumonia is the most common and widely known lung. Bacterial infections of the lungs are a common complication of viral infections as the viruses damage the lungs’ defense system and make the lungs vulnerable to other infections [6]. Both Gram-positive and Pharmaceutics 2020, 12, 1161. Gram-negative bacteria are involved in lung infections and known to cause pneumonia. Fungal infections in the lungs are more common, severe and critical, in immunocompromised patients. This review is focused on the utilization of nanocarriers in pulmonary delivery for effective and safe treatment of pulmonary fungal infections, with special emphasis on PA
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