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Differentially cleaving peptides as a strategy for controlled drug release in human retinal pigment epithelial cells.
- Source :
-
Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2017 Apr 10; Vol. 251, pp. 37-48. Date of Electronic Publication: 2017 Feb 16. - Publication Year :
- 2017
-
Abstract
- Currently, 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).<br /> (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Cathepsin D metabolism
Cell Line
Cell Survival
Drug Delivery Systems
Humans
Hydrophobic and Hydrophilic Interactions
Intravitreal Injections
Nanoparticles
Peptides chemistry
Peptides metabolism
Pigment Epithelium of Eye cytology
Structure-Activity Relationship
Swine
Tissue Distribution
Vitreous Body metabolism
Epithelial Cells metabolism
Peptides pharmacology
Pigment Epithelium of Eye metabolism
Retinal Pigments metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4995
- Volume :
- 251
- Database :
- MEDLINE
- Journal :
- Journal of controlled release : official journal of the Controlled Release Society
- Publication Type :
- Academic Journal
- Accession number :
- 28213274
- Full Text :
- https://doi.org/10.1016/j.jconrel.2017.02.013