Intraocular drug delivery is extraordinarily hampered by the impermeability of defensive barriers of the eye and became, in recent years, a new challenge for pharmaceutical scientists [1-2]. However, only limited success has been gained so far, especially because ocular penetration enhancers, although effective, are penalized by their toxicity and irritation. Cell-penetrating peptides (CPPs) are a group of cationic peptides characterized by really low toxicity, biocompatibility and biodegradability. CPPs shows extraordinary properties in membrane crossing enhancement also for bulky and heavy cargos such as proteins and genes [3-4]. For these reasons, in the present study, we initially investigated whether CPPs could be used as transcorneal penetration enhancers. Results of corneal permeability assay with fl uorophore-labeled CPPs, including penetratin (5,6-CF-RQIKIWFQNRRMKWKK-NH2) and PEP1 (5,6-CF-GGKETWWETWWTEWSQPKKKRKV-NH2) were comparable to the one obtained with ten times lower MW compounds, confirming the penetrating properties of this peptide, probably due to its amphipathicity and positive charge. Images obtained with confocal microscopy suggest that both penetratin and PEP1 quickly penetrate the corneal cells: after only 5 minutes it is possible to visualize the peptides inside the most superficial corneal cells and to follow their diffusion in the underlying cell layers as a function of time. In case of penetratin, a preferential accumulation in the cell nucleus can be appreciated. Due to the promising corneal penetration of PEP1, small library of fl uorophore labeled peptides was designed by mimotopic strategy. Preliminary results obtained led to the identification of interesting sequences potentially useful for the development of new enhancers for a non-invasive ocular drug delivery

Short-length derivatives of cell-penetrating peptides for ocular drug delivery

OSTACOLO, CARMINE;GOMEZ MONTERREY, ISABEL MARIA;NOVELLINO, ETTORE;
2015

Abstract

Intraocular drug delivery is extraordinarily hampered by the impermeability of defensive barriers of the eye and became, in recent years, a new challenge for pharmaceutical scientists [1-2]. However, only limited success has been gained so far, especially because ocular penetration enhancers, although effective, are penalized by their toxicity and irritation. Cell-penetrating peptides (CPPs) are a group of cationic peptides characterized by really low toxicity, biocompatibility and biodegradability. CPPs shows extraordinary properties in membrane crossing enhancement also for bulky and heavy cargos such as proteins and genes [3-4]. For these reasons, in the present study, we initially investigated whether CPPs could be used as transcorneal penetration enhancers. Results of corneal permeability assay with fl uorophore-labeled CPPs, including penetratin (5,6-CF-RQIKIWFQNRRMKWKK-NH2) and PEP1 (5,6-CF-GGKETWWETWWTEWSQPKKKRKV-NH2) were comparable to the one obtained with ten times lower MW compounds, confirming the penetrating properties of this peptide, probably due to its amphipathicity and positive charge. Images obtained with confocal microscopy suggest that both penetratin and PEP1 quickly penetrate the corneal cells: after only 5 minutes it is possible to visualize the peptides inside the most superficial corneal cells and to follow their diffusion in the underlying cell layers as a function of time. In case of penetratin, a preferential accumulation in the cell nucleus can be appreciated. Due to the promising corneal penetration of PEP1, small library of fl uorophore labeled peptides was designed by mimotopic strategy. Preliminary results obtained led to the identification of interesting sequences potentially useful for the development of new enhancers for a non-invasive ocular drug delivery
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11588/611350
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