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

Nicole Zoratto,Pietro Matricardi,Laura Forcina,Giuseppe Familiari,Tommasina Coviello,Chiara Di Meo,Maurizio Mattei,Antonio Musarò,Roberto Matassa,Luciana Mosca

doi:10.3390/pharmaceutics13111781

Nicole Zoratto, Pietro Matricardi + Show 8 more

Open Access

https://doi.org/10.3390/pharmaceutics13111781

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Abstract

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.

Highlights

IntroductionTopical drug delivery is an easy, self-administrable and non-invasive procedure widely used to treat both anterior (e.g., dry eye disease or infections) and posterior (e.g., noninfectious posterior uveitis, diabetic retinopathy, retinal vein occlusion or age-related macular degeneration with macular oedema) segment diseases affecting the ocular tissues [1,2]
Topical drug delivery is an easy, self-administrable and non-invasive procedure widely used to treat both anterior and posterior segment diseases affecting the ocular tissues [1,2]
Compared to other polysaccharide-based NHs intended for ocular drug delivery, the HA-CH NHs prepared for the present work show the further advantage of an easy-fast preparation procedure, which is amenable to their scale-up production as eye-drops

Summary

Introduction

Topical drug delivery is an easy, self-administrable and non-invasive procedure widely used to treat both anterior (e.g., dry eye disease or infections) and posterior (e.g., noninfectious posterior uveitis, diabetic retinopathy, retinal vein occlusion or age-related macular degeneration with macular oedema) segment diseases affecting the ocular tissues [1,2]. Among the different dosage forms, eye drops are the most common method for ocular drug administration [3]. Less than 5% of topically applied therapeutics 4.0/). Pharmaceutics 2021, 13, 1781 reach the intraocular tissues [5]. Systemic administration of drugs (e.g., corticosteroids) usually requires high doses to achieve therapeutic drug levels in the eye, which quite often is accompanied by significant systemic side effects [6]

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