Phage therapy: progress in pharmacokinetics

Abstract

The concept of phage therapy exists in the history and it has been ignored for a long time, but the consequence of drug resistance in pathogen bacteria has forced the forgotten kingdom of phage therapy to be re-explored. However, for the successful implementation and acceptance of phage therapy worldwide, the number of factors need to be addressed. In pharmacology of phage therapy, pharmacodynamics is a straightforward concept, on the other hand, owing to the unique feature of phages to replicate and their high sensitivity, pharmacokinetics is rather complex. In this review, we have discussed pharmacokinetics and some recent advances in delivery systems as to achieve the therapeutically effective concentrations of phage in their activated form.

Bacteriophages for Chronic Wound Treatment: From Traditional to Novel Delivery Systems

“…An example of a successful product, approved for commercialization in 2000 in Georgia, is PhageBioDerm, intended for the treatment of wounds. PhageBioDerm consists of a non-toxic, biodegradable polymeric material containing Pyophage cocktail, ciprofloxacin, benzocaine, α-chymotrypsin, and sodium bicarbonate [107,119]. The Pyophage cocktail formulation targets bacteria that are commonly present in purulent infections (e.g., S. aureus, P. aeruginosa, two Proteus species, E. coli, and several species of Streptococcus) [107].…”

“…The dose of wound preparations relies on the extent of the damage. Although direct injection of phages in the infection site reduces their possible loss, it is a more invasive strategy [119]. Topical application also reduces losses associated with absorption and distribution, increasing the antibacterial activity of phages [119].…”

Comparison of CRISPR and marker based methods for the engineering of phage T7

“…A type I CRISPR system that has previously been used to engineer phage T7 was used in this study, and comprises of the vectors pWUR400 and pWUR397 that carry genes encoding for the enzyme cascade and Cas3 respectively [10]. A third plasmid (pAG_1) was constructed in this study that delivers the gRNA and allows for easy swapping of gRNAs to target different regions ( Figure 3).…”

“…Phages offer a number of advantages (bactericidal agents, rapid discovery, undergo replication at the site of infection) over traditional antibiotics [5][6][7][8][9]. However, there are several limitations to phage therapy, such as narrow host range and limited pharmacokinetics leading to insufficient build-up of phage concentration at the site of infection [10,11].…”

Comparison of CRISPR and Marker-Based Methods for the Engineering of Phage T7

“…Phages offer a number of advantages (bactericidal agents, rapid discovery, undergo replication at the site of infection) over traditional antibiotics [5][6][7][8][9]. However, there are several limitations to phage therapy, such as narrow host range and limited pharmacokinetics leading to insufficient build-up of phage concentration at the site of infection [10,11]. The genetic engineering of phages offers the possibility of overcoming these limitations and allowing phage therapy to be a viable alternative.…”