Bacteriophage Delivery Systems Based on Composite PolyHIPE/Nanocellulose Hydrogel Particles.

Tilen Kopač,Aleš Ručigaj,Ana Lisac,Aleš Podgornik,Matjaž Krajnc,Rok Mravljak

doi:10.3390/polym13162648

Abstract

The role of bacteriophage therapy in medicine has recently regained an important place. Oral phage delivery for gastrointestinal treatment, transport through the stomach, and fast release in the duodenum is one of such applications. In this work, an efficient polyHIPE/hydrogel system for targeted delivery of bacteriophages with rapid release at the target site is presented. T7 bacteriophages were encapsulated in low crosslinked anionic nanocellulose-based hydrogels, which successfully protected phages at pH < 3.9 (stomach) and completely lost the hydrogel network at a pH above 3.9 (duodenum), allowing their release. Hydrogels with entrapped phages were crosslinked within highly porous spherical polyHIPE particles with an average diameter of 24 μm. PolyHIPE scaffold protects the hydrogels from mechanical stimuli during transport, preventing the collapse of the hydrogel structure and the unwanted phage release. On the other hand, small particle size, due to the large surface-to-volume ratio, enables rapid release at the target site. As a consequence, a fast zero-order release was achieved, providing improved patient compliance and reduced frequency of drug administration. The proposed system therefore exhibits significant potential for a targeted drug delivery in medicine and pharmacy.

Highlights

In recent years, the spread of antibiotic-resistant bacteria became a global health problem making potential alternatives like bacteriophages an important field of study [1].Bacteriophages are natural killers of bacteria, which lyse bacteria to produce new progeny viruses [2]
The success of phage therapy depends on bacterial physiological state and phage stability, survival, and consistent phage titer for a stable dosage delivered at the site of infection [7,8]
The experimental work includes the preparation of an efficient system for encapsulation of T7 bacteriophages in a release medium with a pH of 2 and activation of the Polymers 2021, 13, 2648 release at the highest possible release rate in the medium at a pH of 5–7

Summary

Introduction

The spread of antibiotic-resistant bacteria became a global health problem making potential alternatives like bacteriophages an important field of study [1].Bacteriophages are natural killers of bacteria, which lyse bacteria to produce new progeny viruses [2]. Phage therapy is intriguing since phage self-replication ability leads to a local increase in their concentration, and the narrow host specificity of phages ensures the lack of broad off-target effects [3,4,5,6]. The success of phage therapy depends on bacterial physiological state and phage stability, survival, and consistent phage titer (concentration) for a stable dosage delivered at the site of infection [7,8]. Several studies have demonstrated that low pH can affect and inactivate phage populations [10,11]. Phage T7 used in our experiments remains stable at pH 6–8 and is completely inactivated at pH below 3 [12]. Phages were mostly encapsulated in liposomes [13,14], and for other infections such as burn wounds, biofilms on implants, and root canal infections, phages were encapsulated in micropar-

Objectives

Methods

Results

Conclusion