Encapsulation and Delivery of Therapeutic Phages
Abstract
Delivery of therapeutic compounds to the site of action is crucial. While many chemical substances such as beta-lactam antibiotics can reach therapeutic levels in most parts throughout the human body after administration, substances of higher molecular weight such as therapeutic proteins may not be able to reach the site of action (e.g. an infection), and are therefore ineffective. In the case of therapeutic phages, i.e. viruses that infect microbes that can be used to treat bacterial infections, this problem is exacerbated; not only are phages unable to penetrate tissues, but phage particles can be cleared by the immune system and phage proteins are rapidly degraded by enzymes or inactivated by the low pH in the stomach. Yet, the use of therapeutic phages is a highly promising strategy, in particular for infections caused by bacteria that exhibit multi-drug resistance. Clinicians increasingly encounter situations where no treatment options remain available for such infections, where antibiotic compounds are ineffective. While the number of drug-resistant pathogens continues to rise due to the overuse and misuse of antibiotics, no new compounds are becoming available as many pharmaceutical companies discontinue their search for chemical antimicrobials. In recent years, phage therapy has undergone massive innovation for the treatment of infections caused by pathogens resistant to conventional antibiotics. While most therapeutic applications of phages are well described in the literature, other aspects of phage therapy are less well documented. In this review, we focus on the issues that are critical for phage therapy to become a reliable standard therapy and describe methods for efficient and targeted delivery of phages, including their encapsulation.