RRC ID 62023
Author Faber K, Zorzi GK, Brazil NT, Rott MB, Teixeira HF.
Title siRNA-loaded liposomes: Inhibition of encystment of Acanthamoeba and toxicity on the eye surface.
Journal Chem Biol Drug Des
Abstract Current treatments for Acanthamoeba keratitis are unspecific. Because of the presence of the resilient cyst form of the parasite, the infection is persistent. Silencing the key protein of cyst formation, glycogen phosphorylase, has shown potential for reducing encystment processes of the Acanthamoeba trophozoite. However, a suitable carrier to protect and deliver siRNA sequences is still needed.
DOTAP:DOPE:DSPE-PEG liposomes were prepared by three different techniques and used to associate a therapeutic siRNA sequence. Liposomes prepared by film hydration followed by membrane extrusion were considered the most adequate ones with average size of 250 nm and zeta potential of +45 mV, being able to associate siRNA for at least 24 hr in culture medium. siRNA-liposomes could inhibit up to 66% of the encystment process. Cell viability studies demonstrated MTT reduction capacity higher than 80% after 3 hr incubation with this formulation. After 24 hr of incubation, LDH activity ranged for both the formulations from around 4% to 40%. In vivo tolerance studies in mice showed no macroscopic alteration in the eye structures up to 24 hr after eight administrations during 1 day. Histological studies showed regular tissue architecture without any morphological alteration. Overall, these results suggest that the formulations developed are a promising new strategy for the treatment of ocular keratitis caused by Acanthamoeba spp.
Volume 90(3)
Pages 406-416
Published 2017-9-1
DOI 10.1111/cbdd.12958
PMID 28135787
MeSH Acanthamoeba / drug effects* Acanthamoeba / enzymology Acanthamoeba / metabolism Animals Cell Line Cell Survival / drug effects Cornea / drug effects* Cornea / metabolism Cornea / parasitology Cornea / pathology Eye / drug effects Eye / metabolism Eye / parasitology Eye / pathology Glycogen Phosphorylase / antagonists & inhibitors Glycogen Phosphorylase / genetics Glycogen Phosphorylase / metabolism Humans Liposomes / chemistry* Liposomes / toxicity Male Mice Particle Size Protozoan Proteins / antagonists & inhibitors Protozoan Proteins / genetics Protozoan Proteins / metabolism RNA Interference RNA, Small Interfering / chemistry RNA, Small Interfering / metabolism* RNA, Small Interfering / pharmacology*
IF 2.548
Human and Animal Cells HCE-T(RCB2280)