Artificial Protein Coronas Enable Controlled Interaction with Corneal Epithelial Cells: New Opportunities for Ocular Drug Delivery

Topical administration is the most convenient route for ocular drug delivery, but only a minor fraction is retained in the precorneal pocket. To overcome this limitation, numerous drug delivery systems (DDS) have been developed. The protein corona (PC) is the layer of biomolecules (e.g., proteins, s...

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Main Authors: Carlo Astarita, Sara Palchetti, Mina Massaro-Giordano, Marina Di Domenico, Francesco Petrillo, Silvia Boffo, Giulio Caracciolo, Antonio Giordano
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/13/6/867
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author Carlo Astarita
Sara Palchetti
Mina Massaro-Giordano
Marina Di Domenico
Francesco Petrillo
Silvia Boffo
Giulio Caracciolo
Antonio Giordano
author_facet Carlo Astarita
Sara Palchetti
Mina Massaro-Giordano
Marina Di Domenico
Francesco Petrillo
Silvia Boffo
Giulio Caracciolo
Antonio Giordano
author_sort Carlo Astarita
collection DOAJ
description Topical administration is the most convenient route for ocular drug delivery, but only a minor fraction is retained in the precorneal pocket. To overcome this limitation, numerous drug delivery systems (DDS) have been developed. The protein corona (PC) is the layer of biomolecules (e.g., proteins, sugars, lipids, etc.) that forms around DDS in physiological environments by non-covalent interaction. The PC changes the DDS physical–chemical properties, providing them with a completely novel biological identity. The specific involvement of PC in ocular drug delivery has not been addressed so far. To fulfill this gap, here we explored the interaction between a library of four cationic liposome-DNA complexes (lipoplexes) and mucin (MUC), one of the main components of the tear film. We demonstrate that MUC binds to the lipoplex surface shifting both their size and surface charge and reducing their absorption by primary corneal epithelial cells. To surpass such restrictions, we coated lipoplexes with two different artificial PCs made of Fibronectin (FBN) and Val-Gly-Asp (VGA) tripeptide that are recognized by receptors expressed on the ocular surface. Both these functionalizations remarkedly boosted internalization in corneal epithelial cells with respect to pristine (i.e., uncoated) lipoplexes. This opens the gateway for the exploitation of artificial protein corona in targeted ocular delivery, which will significantly influence the development of novel nanomaterials.
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spelling doaj.art-ee3ef9eed08940a3bc4dbd93ad317b142023-11-21T23:51:49ZengMDPI AGPharmaceutics1999-49232021-06-0113686710.3390/pharmaceutics13060867Artificial Protein Coronas Enable Controlled Interaction with Corneal Epithelial Cells: New Opportunities for Ocular Drug DeliveryCarlo Astarita0Sara Palchetti1Mina Massaro-Giordano2Marina Di Domenico3Francesco Petrillo4Silvia Boffo5Giulio Caracciolo6Antonio Giordano7Sbarro Institute for Cancer Research and Molecular Medicine, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USADepartment of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 291, 00161 Rome, ItalySbarro Institute for Cancer Research and Molecular Medicine, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USASbarro Institute for Cancer Research and Molecular Medicine, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USADepartment of Ophthalmology, A. O. U. Policlinic-Vittorio Emanuele, 95124 Catania, ItalySbarro Institute for Cancer Research and Molecular Medicine, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USADepartment of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 291, 00161 Rome, ItalySbarro Institute for Cancer Research and Molecular Medicine, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USATopical administration is the most convenient route for ocular drug delivery, but only a minor fraction is retained in the precorneal pocket. To overcome this limitation, numerous drug delivery systems (DDS) have been developed. The protein corona (PC) is the layer of biomolecules (e.g., proteins, sugars, lipids, etc.) that forms around DDS in physiological environments by non-covalent interaction. The PC changes the DDS physical–chemical properties, providing them with a completely novel biological identity. The specific involvement of PC in ocular drug delivery has not been addressed so far. To fulfill this gap, here we explored the interaction between a library of four cationic liposome-DNA complexes (lipoplexes) and mucin (MUC), one of the main components of the tear film. We demonstrate that MUC binds to the lipoplex surface shifting both their size and surface charge and reducing their absorption by primary corneal epithelial cells. To surpass such restrictions, we coated lipoplexes with two different artificial PCs made of Fibronectin (FBN) and Val-Gly-Asp (VGA) tripeptide that are recognized by receptors expressed on the ocular surface. Both these functionalizations remarkedly boosted internalization in corneal epithelial cells with respect to pristine (i.e., uncoated) lipoplexes. This opens the gateway for the exploitation of artificial protein corona in targeted ocular delivery, which will significantly influence the development of novel nanomaterials.https://www.mdpi.com/1999-4923/13/6/867ocular drug deliveryprotein coronaocular surface
spellingShingle Carlo Astarita
Sara Palchetti
Mina Massaro-Giordano
Marina Di Domenico
Francesco Petrillo
Silvia Boffo
Giulio Caracciolo
Antonio Giordano
Artificial Protein Coronas Enable Controlled Interaction with Corneal Epithelial Cells: New Opportunities for Ocular Drug Delivery
Pharmaceutics
ocular drug delivery
protein corona
ocular surface
title Artificial Protein Coronas Enable Controlled Interaction with Corneal Epithelial Cells: New Opportunities for Ocular Drug Delivery
title_full Artificial Protein Coronas Enable Controlled Interaction with Corneal Epithelial Cells: New Opportunities for Ocular Drug Delivery
title_fullStr Artificial Protein Coronas Enable Controlled Interaction with Corneal Epithelial Cells: New Opportunities for Ocular Drug Delivery
title_full_unstemmed Artificial Protein Coronas Enable Controlled Interaction with Corneal Epithelial Cells: New Opportunities for Ocular Drug Delivery
title_short Artificial Protein Coronas Enable Controlled Interaction with Corneal Epithelial Cells: New Opportunities for Ocular Drug Delivery
title_sort artificial protein coronas enable controlled interaction with corneal epithelial cells new opportunities for ocular drug delivery
topic ocular drug delivery
protein corona
ocular surface
url https://www.mdpi.com/1999-4923/13/6/867
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