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dc.contributor.authorBhattacharya M
dc.contributor.authorSarkhel S
dc.contributor.authorPeltoniemi J
dc.contributor.authorBroadbridge R
dc.contributor.authorTuomainen M
dc.contributor.authorAuriola S
dc.contributor.authorUrtti A
dc.date.accessioned2017-07-19T11:48:38Z
dc.date.available2017-07-19T11:48:38Z
dc.date.issued2017
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/3573
dc.description.abstractCurrently, drug delivery to the posterior eye segment relies on intravitreal injections of therapeutics. This approach requires frequent injections and does not guarantee drug delivery to intracellular targets. Controlled release systems and nanoparticles are being investigated to mitigate these challenges but most of these approaches lack translational success to the clinics. In our present study, we report a peptide-based delivery system that utilizes enzyme assisted cleavable linkers to release conjugated cargo within the retinal pigment epithelial (RPE) cells. Peptide linkers with differential cleavage rates were developed and tested in the vitreous humor, RPE cell homogenates and intact RPE cells. Selected peptide linkers were conjugated to cell penetrating peptides and d-peptide cargoes. The peptide-based delivery systems were non-toxic to the RPE cells, chemically stable in porcine vitreous and delivered cargo prototypes (hydrophobic & hydrophilic) to the RPE cells. Importantly, we show quantitatively with LC/MS analytics that the intracellular cargo release is controlled by the sequence of the peptide linker. The controlled cleavage of the peptide linkers is not only a useful strategy for intracellular drug delivery to the RPE targets but might also be useful in utilizing the RPE cells as mediators of drug delivery to intracellular targets and surrounding tissues (such as neural retina and choroid).en
dc.language.isoENen
dc.publisherElsevier BVen
dc.relation.ispartofseriesJOURNAL OF CONTROLLED RELEASEen
dc.relation.urihttps://doi.org/10.1016/j.jconrel.2017.02.013en
dc.rightsCC BY-NC-ND https://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectDrug deliveryen
dc.subjectOcular therapeuticsen
dc.subjectRetinaRetinal pigment epitheliumen
dc.subjectDrug targetingen
dc.subjectPeptideen
dc.subjectConjugationen
dc.titleDifferentially cleaving peptides as a strategy for controlled drug release in human retinal pigment epithelial cellsen
dc.description.versionfinal draften
dc.contributor.departmentSchool of Pharmacy, Activitiesen
uef.solecris.id46520884en
dc.type.publicationinfo:eu-repo/semantics/articleen
dc.rights.accessrights© Elsevier BVen
dc.relation.doi10.1016/j.jconrel.2017.02.013en
dc.description.reviewstatuspeerRevieweden
dc.format.pagerange37-48en
dc.relation.issn0168-3659en
dc.relation.volume251en
dc.rights.accesslevelopenAccessen
dc.type.okmA1en
dc.type.versioninfo:eu-repo/semantics/acceptedVersionen


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