Design of respirable sprayed microparticles of encapsulated bacteriophages

Abstract

Antibiotic resistance is exponentially increasing, and the number of deaths caused by bacterial infections is expected to surge. When dealing with the respiratory system, inefficient antibiotics heighten the chance of death from bacterial infection. However, the alternatives to antibiotics are limited. Bacteriophages are a valid option since they can target a specific type of bacterium. Bacteriophages are highly specific and can avoid any side effects when delivered. However, their poor stability makes their use inefficient. Encapsulation is commonly used to protect any bioactive compound for different types of delivery. In the case of respiratory delivery, particle engineering is used to generate stable dry powders to target the nasal or lung areas. This review article provides a guideline for engineering a process of nasal dry powders of encapsulated bacteriophages.

Phage Delivery Strategies for Biocontrolling Human, Animal, and Plant Bacterial Infections: State of the Art

“…Encapsulation may be defined as the process of the entrapment of phage particles by coating them with appropriate (bio)polysaccharides, forming a protective shell, to segregate them from the surrounding environment. Such a shell favors the protection of phage virions from external conditions and may also favor adhesion to specific susceptible bacterial cells [ 52 ]. The aim of (micro)encapsulation is, thus, to create a micro-environment in which phage virions will survive under the harsh GIT conditions, in processing and storage conditions, during desiccation processes, and other adverse biotic or abiotic conditions [ 64 ].…”

“…At the moment, pulmonary phage therapy has been predominantly applied in people who suffer from muco-obstructive lung diseases such as cystic fibrosis, non-cystic fibrosis, bronchiectasis, primary ciliary dyskinesia, and chronic obstructive pulmonary disease [ 131 ]. Besides this, a small number of phages have been isolated and utilized to fight common bacterial infections in the lungs, due to Streptococcus pneumoniae , Haemophilus influenzae , Staphylococcus aureus , Mycobacterium tuberculosis , Corynebacterium , Neisseria , Fusobacterium , Moraxella catarrhalis , and Pseudomonas aeruginosa [ 52 ].…”

“…The liquid form is easier to prepare and has a not-so-long average shelf half-life, but it is a form that lacks accuracy and is more prone to contamination. On the other hand, dry powders, through lyophilization or other dehydration techniques, show on average a longer preservation and stability of the phage virion’s lytic bioactivity [ 52 ].…”

The Medicinal Phage—Regulatory Roadmap for Phage Therapy under EU Pharmaceutical Legislation

“…Possible dosage forms under investigation include the incorporation of phages into gels, ointments, gauze, or liquid solutions for injection [ 14 , 77 , 96 , 101 , 102 , 103 , 104 , 105 ]. In addition, inhalable phage therapeutics are being developed for the treatment of respiratory diseases [ 71 , 106 , 107 ].…”