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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.

Hyaluronan-Cholesterol Nanogels for the Enhancement of the Ocular Delivery of Therapeutics