Hyaluronan-Cholesterol Nanogels for the Enhancement of the Ocular Delivery of Therapeutics
Nicole Zoratto,
Laura Forcina,
Roberto Matassa,
Luciana Mosca,
Giuseppe Familiari,
Antonio Musarò,
Maurizio Mattei,
Tommasina Coviello,
Chiara Di Meo,
Pietro Matricardi
Affiliations
Nicole Zoratto
Department of Drug Chemistry and Technologies, Sapienza University of Rome, 00185 Roma, Italy
Laura Forcina
DAHFMO-Unit of Histology and Medical Embryology, Sapienza University of Rome, Via A. Scarpa, 14, 00161 Rome, Italy
Roberto Matassa
Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Section of Human Anatomy, Sapienza University of Rome, Via A. Borelli 50, 00161 Rome, Italy
Luciana Mosca
Department of Biochemical Sciences “A. Rossi Fanelli”, Sapienza University of Rome, 00185 Roma, Italy
Giuseppe Familiari
Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Section of Human Anatomy, Sapienza University of Rome, Via A. Borelli 50, 00161 Rome, Italy
Antonio Musarò
DAHFMO-Unit of Histology and Medical Embryology, Sapienza University of Rome, Via A. Scarpa, 14, 00161 Rome, Italy
Maurizio Mattei
Interdepartmental Center for Comparative Medicine, Alternative Techniques and Aquaculture (CIMETA), University of Rome “Tor Vergata”, Via Montpellier 1, 00133 Rome, Italy
Tommasina Coviello
Department of Drug Chemistry and Technologies, Sapienza University of Rome, 00185 Roma, Italy
Chiara Di Meo
Department of Drug Chemistry and Technologies, Sapienza University of Rome, 00185 Roma, Italy
Pietro Matricardi
Department of Drug Chemistry and Technologies, Sapienza University of Rome, 00185 Roma, Italy
The anatomy and physiology of the eye strongly limit the bioavailability of locally administered drugs. The entrapment of therapeutics into nanocarriers represents an effective strategy for the topical treatment of several ocular disorders, as they may protect the embedded molecules, enabling drug residence on the ocular surface and/or its penetration into different ocular compartments. The present work shows the activity of hyaluronan-cholesterol nanogels (NHs) as ocular permeation enhancers. Thanks to their bioadhesive properties, NHs firmly interact with the superficial corneal epithelium, without penetrating the stroma, thus modifying the transcorneal penetration of loaded therapeutics. Ex vivo transcorneal permeation experiments show that the permeation of hydrophilic drugs (i.e., tobramycin and diclofenac sodium salt), loaded in NHs, is significantly enhanced when compared to the free drug solutions. On the other side, the permeation of hydrophobic drugs (i.e., dexamethasone and piroxicam) is strongly dependent on the water solubility of the entrapped molecules. The obtained results suggest that NHs formulations can improve the ocular bioavailability of the instilled drugs by increasing their preocular retention time (hydrophobic drugs) or facilitating their permeation (hydrophilic drugs), thus opening the route for the application of HA-based NHs in the treatment of both anterior and posterior eye segment diseases.
