Inhaled Liposomal Antimicrobial Delivery in Lung Infections

Abstract

The management of difficult-to-treat acute and chronic respiratory infections (infections in cystic fibrosis, non-cystic fibrosis bronchiectasis, immunocompromised and mechanically ventilated patients) and difficult-to-treat pathogens (including multidrug-resistant strains) has become a challenge in clinical practice. The arsenal of conventional antibiotic drugs can be limited by tissue penetration, toxicities, or increasing antibiotic resistance. Inhaled antimicrobials are an interesting therapeutic approach for optimizing the management of respiratory infections. Due to extensive developments in liposome technology, a number of inhaled liposome-based antibiotic and antifungal formulations are available for human use and many products are undergoing clinical trials. Liposomes are biocompatible, biodegradable, and nontoxic vesicles able to encapsulate and carry antimicrobials, enhancing the therapeutic index of various agents and retention at the desired target within the lung. Liposomes reduce drug toxicity and improve tolerability, leading to better compliance and to decreased respiratory side effects. The aim of this article was to provide an up-to-date overview of nebulized liposomal antimicrobials for lung infections (with a special focus on liposomal amikacin, tobramycin, ciprofloxacin, and amphotericin B for inhalation), discussing the feasibility and therapeutic potential of these new strategies of preventing and treating bacteria, mycobacterial and fungal infections.

Liposomes as Antibiotic Delivery Systems: A Promising Nanotechnological Strategy against Antimicrobial Resistance

“…Despite the improvements in inhalation delivery technologies, the majority of the formulations are still hampered by the short half-life and rapid clearance of the antibiotic from the lung, which could result in sub-inhibitory antibiotic concentrations and decreased antimicrobial efficacy [ 51 , 52 ]. To surpass this issue, liposomes are being developed to guarantee a sustained release of the antibiotics in aerosol formulations, allowing maintenance of antibiotic concentrations above MIC without the need for frequent dosing [ 52 ].…”

“…Despite the improvements in inhalation delivery technologies, the majority of the formulations are still hampered by the short half-life and rapid clearance of the antibiotic from the lung, which could result in sub-inhibitory antibiotic concentrations and decreased antimicrobial efficacy [ 51 , 52 ]. To surpass this issue, liposomes are being developed to guarantee a sustained release of the antibiotics in aerosol formulations, allowing maintenance of antibiotic concentrations above MIC without the need for frequent dosing [ 52 ]. Antibiotic liposomal aerosol formulations have been developed for a variety of pathogens including Pseudomonas aeruginosa and Mycobacterium spp., with amikacin, ciprofloxacin and tobramycin being some of the antibiotics considered for this application, as reviewed by Basseti and collaborators [ 52 ].…”

“…To surpass this issue, liposomes are being developed to guarantee a sustained release of the antibiotics in aerosol formulations, allowing maintenance of antibiotic concentrations above MIC without the need for frequent dosing [ 52 ]. Antibiotic liposomal aerosol formulations have been developed for a variety of pathogens including Pseudomonas aeruginosa and Mycobacterium spp., with amikacin, ciprofloxacin and tobramycin being some of the antibiotics considered for this application, as reviewed by Basseti and collaborators [ 52 ]. Overall, significant improvements in bacterial clearance have been observed, for example, for inhaled ciprofloxacin liposomal formulations for both P. aeruginosa and non-tuberculosis mycobacteria [ 51 , 53 , 54 ].…”

Approaches to Targeting Bacterial Biofilms in Cystic Fibrosis Airways

“…More recently, a randomized trial using the same preparation for CF patients with NTM infection, resulted in culture conversion and improved performance on a 6 min-walk-test, although it did not meet the primary endpoint of reduction of sputum bacterial density [ 38 ]. The approach of developing liposomal formulations of antibiotics is the focus of other extensive reviews on the subject [ 37 , 39 , 40 ].…”

Initial In Vivo Evaluation of a Novel Amikacin-Deoxycholate Hydrophobic Salt Delivers New Insights on Amikacin Partition in Blood and Tissues

“…Amk can treat a wide range of infections by binding the ribosomal 30 s subunit and inhibiting protein synthesis [ 14 ]. The literature on Amk pulmonary delivery includes mainly liquid aerosols [ 15 , 16 , 17 , 18 ] and liposomes [ 19 , 20 , 21 , 22 , 23 , 24 ] and sporadic works on solid lipid nanoparticles [ 25 ] and self-emulsifying drug delivery systems [ 26 ]. An inhalable liposomal form of Amk (Arikayce ® ) has found recent approval by the FDA for pneumonia treatment [ 20 , 21 , 27 ].…”