Antibiotic-Loaded Polymersomes for Clearance of Intracellular Burkholderia thailandensis

Abstract

Melioidosis caused by the facultative intracellular pathogen Burkholderia pseudomallei is difficult to treat due to poor intracellular bioavailability of antibiotics and antibiotic resistance. In the absence of novel compounds, polymersome (PM) encapsulation may increase the efficacy of existing antibiotics and reduce antibiotic resistance by promoting targeted, infection-specific intracellular uptake. In this study, we developed PMs composed of widely available poly(ethylene oxide)-polycaprolactone block copolymers and demonstrated their delivery to intracellular B. thailandensis infection using multispectral imaging flow cytometry (IFC) and coherent anti-Stokes Raman scattering microscopy. Antibiotics were tightly sequestered in PMs and did not inhibit the growth of free-living B. thailandensis. However, on uptake of antibiotic-loaded PMs by infected macrophages, IFC demonstrated PM colocalization with intracellular B. thailandensis and a significant inhibition of their growth. We conclude that PMs are a viable approach for the targeted antibiotic treatment of persistent intracellular Burkholderia infection.

Multipronged Micelles–Hydrogel for Targeted and Prolonged Drug Delivery in Chronic Wound Infections

“…aureus, Escherichia coli, Salmonella , and some other bacterial pathogens are inclined to invade host cells, especially the epithelial cells in the infected wound . The cellular invading pathogens could hardly be removed completely due to their resistance to high concentrations of extracellular antibiotics, which therefore leads to persistent infections and further disrupts the wound healing process. , Increasing the intracellular abundance of antibiotics is an effective way to promote the antibacterial efficacy . Although strategies including developing new drugs and adjuvants for killing intracellular bacteria, inhibiting drug efflux pumps, enhancing cellular autophagy, and establishing photothermally sensitive antibacterial materials have been widely explored, , few achievements have been gained due to the disadvantages of a complex system, low universality, time-consuming research, development costs, and high technical requirements.…”

Nanotheranostics to target antibiotic-resistant bacteria: Strategies and applications

“…Due to low antibiotic bioavailability and commonly exhibiting AMR, the facultative Burkholderia pseudomallei is a microorganism challenging to target with typical antibiotics. However, Porges et al used imaging flow cytometry (IFC), to demonstrate the colocalization of polymersome with intracellular B. thailandensis, which suppresses their proliferation upon the incorporation of antibiotic-loaded polymersomes by infected macrophages [174]. Furthermore, compared to free antibiotics or polymersome alone, polymersome-encapsulated metronidazole or doxycycline dramatically reduces the intracellular gram-negative anaerobe Porphyromonas gingivalis, which is associated with periodontal disease [175].…”

Epsilon-poly-l-lysine conjugated erythromycin for enhanced antibiotic therapy

“…Various antibiotic loaded nanoparticles were designed, which can enhance the therapeutic efficacy of conventional antibiotics by inhibiting degradation, improving biodistribution, enhancing biolm penetration, enhancing drug-bacteria interaction, and so on. [30][31][32][33] Chemical modication of conventional antibiotics is another effective way to improve the therapeutic efficacy. As a typical example, Cterminus guanidine modication of vancomycin was reported for enhanced antibacterial activity.…”