Posterior Segment Ophthalmic Drug Delivery: Role of Muco-Adhesion with a Special Focus on Chitosan

Abstract

Posterior segment eye diseases (PSEDs) including age macular degeneration (AMD) and diabetic retinopathy (DR) are amongst the major causes of irreversible blindness worldwide. Due to the numerous barriers encountered, highly invasive intravitreal (IVT) injections represent the primary route to deliver drugs to the posterior eye tissues. Thus, the potential of a more patient friendly topical route has been widely investigated. Mucoadhesive formulations can decrease precorneal clearance while prolonging precorneal residence. Thus, they are expected to enhance the chances of adherence to corneal and conjunctival surfaces and as such, enable increased delivery to the posterior eye segment. Among the mucoadhesive polymers available, chitosan is the most widely explored due to its outstanding mucoadhesive characteristics. In this review, the major PSEDs, their treatments, barriers to topical delivery, and routes of topical drug absorption to the posterior eye are presented. To enable the successful design of mucoadhesive ophthalmic drug delivery systems (DDSs), an overview of mucoadhesion, its theory, characterization, and considerations for ocular mucoadhesion is given. Furthermore, chitosan-based DDs that have been explored to promote topical drug delivery to the posterior eye segment are reviewed. Finally, challenges of successful preclinical to clinical translation of these DDSs for posterior eye drug delivery are discussed.

Applications of Chitosan-Alginate-Based Nanoparticles—An Up-to-Date Review

“…Its biocompatibility, biodegradability, nontoxicity, mucoadhesivity, and hemocompatibility are ideal characteristics for designing nanocarriers with controlled delivery and sustained release of various therapeutics [10,[20][21][22][23][24][25][26][27]. Chitosan has shown great promise in nanodelivery for the treatment of cancer [28][29][30], diabetes [31][32][33], eye diseases [34][35][36], infectious diseases [37][38][39][40][41], and more, being also recently employed in the delivery of vaccines [42][43][44][45].…”

Lipid Nanoparticles as a Promising Drug Delivery Carrier for Topical Ocular Therapy—An Overview on Recent Advances

“…Thus, retention of nanoparticles within the cul-de-sac after administration is essential for sustained drug release effect and prolonged therapeutic effect. To avoid potential non-specific interaction with non-corneal surfaces, the liposome is coated with mucoadhesive polymers [ 170 ]. To improve the targeted corneal attachment, monoclonal antibodies linked to antiviral-loaded liposomes have been developed [ 171 ].…”

Fluorescent Nanosystems for Drug Tracking and Theranostics: Recent Applications in the Ocular Field

“…Efforts are made to design systems that have the ability to improve retention on the ocular surface. In this respect, the use of chitosan to improve the delivery of drugs into the eye tissues for its properties as a mucoadhesive agent, controlled drug release and permeation enhancer is interesting [ 24 ]. It is used in conjugation with a drug, such as in the study of Dubashynskaya et al, to improve the intravitreal delivery of dexamethasone [ 109 ].…”

“…Nanotechnology represents a field of recent interest to overcome these issues. One potential strategy for improving drug delivery to the different eye tissues uses nanocarriers with specific size and surface properties, designed to ensure successful achievement of the drug to the target tissue, as well as the potential for a controlled release of the loaded drug, reducing the frequency of treatment and improving the retention time on the corneal surface [ 22 , 23 , 24 ]. Currently, the most widely studied nanosystems are used in the treatment of anterior eye diseases such as cataracts [ 25 ], glaucoma [ 26 ], dry eye syndrome [ 27 ], keratitis [ 28 ], conjunctivitis [ 29 ] and uveitis [ 30 ], but also posterior eye diseases such as retinitis [ 31 ], macular degeneration [ 32 ], endophthalmitis [ 33 ] and ocular tumors [ 34 ].…”

“…The greater surface area (in humans, about 17 times bigger than the cornea) and the presence of larger pore sizes promote increased permeability compared to the cornea. However, mucus and the presence of lymphatics and vasculature increases systemic leakage [ 24 , 38 ]. In ocular topical administration, reaching the posterior portion is size-dependent [ 65 ].…”