The ever-growing number of persistent antibiotic-resistant bacterial strains in the human population assumes a search for novel forms and methods of treatment of infectious diseases. The aim of this research was to design a suppository administration form based on a combined bacteriophage substance.
A formulation has been designed and a pilot technology tested for producing suppositories based on a bacteriophage cocktail with each strain at a titer of at least 108 pfu/supp. The concentration of phages in feces, urine and blood of the rabbits reached its peak (104-106 pfu/ml) 4.5-6 hours after a single rectal administration of suppositories. Notably, bacteriophages of a smaller (according to the data of electronic microscopy) size were delivered from the rectal lumen into the bloodstream and, consequently, into the urinal tract faster (within 3 hours). All of the bacteriophage strains were defined in the rabbits in insignificant quantities 24 hours after the suppositories had been administered. Functional and morphological adequacy of the virulent particles persistent in the animals was confirmed by both the possibility to define the specific activity of bacteriophages isolated from clinical material by the Gratia method and the presence in the serum of IgG-antibodies for bacteriophage capsid on the 23rd day after a single administration of suppositories in the rabbits. In an in vitro neutralization assay non-specific protective factors reduced the initial titer of phage lysate by 102-104 pfu/ml, whereas the serum of an immunized animal completely blocked the lytic activity of phage particles. Pharmacokinetic curves of phage titers in feces, urine and blood were completely identical in shape, which testified, along with the formation of antibodies specific to protein structures of viral particles, for systemic pattern of performance of bacteriophages, infiltrating after the per rectum administration into the bloodstream, liver, gallbladder, kidneys, bladder, small and large intestine of lab animals.