In vitro evaluation of 4,4'-trimethylenedipyridinium and 4,4'-trimethylenedipiperidinium-based polycationic polymers...

Corneal exposure to trophozoites of Acanthamoeba spp. may lead to Acanthamoeba keratitis (AK)-a rare, but sight-threatening disease-with a risk of recurrence due to residual stromal cysts. With polyhexanide (PHMB) and chlorhexidine (CHX) often constituting the standard regimen of therapy, polymeric compounds for the treatment of AK have shifted into the focus of research. In this study, the effectiveness of four 4,4'-trimethylenedipyridinium (TMDPy), 4,4'-trimethylenedipiperidinium (TMDPi)-based polymers, and polyquaternium-1 on Acanthamoeba trophozoites and cysts has been evaluated and their interactions with cells characterized. A total eradication assay was performed to assess the efficacy of the investigated compounds, while its effects on host cells and the barrier integrity of epithelial cell layers were evaluated via MTT assays and the relative reduction of transepithelial electrical resistance (TEER). The 4,4'-trimethylenedipyridinium and 4,4'-trimethylenedipiperidinium-based compounds exhibited a high efficacy against trophozoites (< 20 µg/mL), while the cysticidal activity proved to be considerably lower (< 500 µg/mL). The detrimental effect on viability of host cells was time-dependent, while a near total reduction of TEER was observed within the first 15 min of exposure, leading to the conclusion that this class of polymers may not be adequate for therapeutic purposes, but possibly find use as preservatives for contact lens storage solutions.