Author(s): Silva, Maria Daniela ; Ray, Kaelin ; Gama, F. M. ; Remenschneider, Aaron K. ; Sillankorva, Sanna
Date: 2022
Persistent ID: https://hdl.handle.net/1822/77190
Origin: RepositóriUM - Universidade do Minho
Subject(s): drug delivery; endolysin; liposome; MSlys; transtympanic; Streptococcus pneumoniae; Science & Technology
An increase in bacterial resistance to systemic antibiotics has sparked interest into alternative antimicrobial compounds as well as methods for effective local, non-invasive drug delivery. Topical treatments, however, may be hindered by the presence of biological barriers, such as the tympanic membrane in the case of otitis media. Herein, the transtympanic permeation ability of liposomes loaded with the pneumococcal endolysin MSlys and of free MSlys was evaluated ex vivo. MSlys loaded in PEGylated liposomes showed an increased permeation across human tympanic membranes, as compared to its free form, being able to reduce the pneumococcal cell load after 2 h of permeation. However, antipneumococcal activity was no longer detected after 4 h of permeation and hydrolysis of the endolysin was observed after an extended incubation time ( 48 h). This work provides a first assessment of a successful, non-invasive delivery method for endolysins across an intact tympanic membrane. Findings have implications for non-systemic, local treatment of otitis media.
This study was partially supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2020 unit. MDS acknowledges support from the FCT doctoral fellowship, reference SFRH/BD/128825/2017 and COVID/BD/152363/2022. SS acknowledges funding by FCT, through the individual scientific employment program contract (2020.03171.CEECIND). AKR acknowledges funding to support this project from the Wyss Institute for Biologically Inspired Engineering at Harvard University and from NIH NIDCD K08-DC018575
info:eu-repo/semantics/publishedVersion
