Penetration Enhancers for Topical Drug Delivery to the Ocular Posterior Segment-A Systematic Review.

Abhinav Thareja,Zubair Ahmed,Helen Hughes,Jenni J Hakkarainen,Carmen Alvarez-Lorenzo

doi:10.3390/pharmaceutics13020276

Abstract

There is an unmet clinical need for eye drop formulations to efficiently treat the diseases of the posterior ocular segment by non-invasive topical administration. Here, we systematically reviewed the literature on ocular penetration enhancers and their ability to transfer drugs to the posterior segment of the eye in experimental studies. Our aim was to assess which penetration enhancer is the most efficient at delivering drugs to the posterior segment of the eye, when topically applied. We conducted a comprehensive search in three electronic databases (Ovid Embase, Ovid MEDLINE, and PubMed) to identify all the relevant manuscripts reported on ocular penetration enhancers based on the PRISMA guidelines. We identified 6540 records from our primary database search and filtered them per our inclusion/exclusion criteria to select a final list of 14 articles for qualitative synthesis. Of these, 11 studies used cell penetrating peptides (CPPs), 2 used chitosan, and 1 used benzalkonium chloride (BAC) as the penetration enhancer. Cationic and amphipathic CPPs, transactivator of transcription (TAT), and penetratin can be inferred to be the best among all the identified penetration enhancers for drug delivery to the fundus oculi via topical eye drop instillation. Further high-quality experimental studies are required to ascertain their quantitative efficacy.

Highlights

Eye diseases originating in the posterior segment ocular tissues, mainly in the retinachoroid, are a major cause of visual impairment across the globe
It is estimated that worldwide, around 2.2 billion people have some sort of visual impairment and out of these, people affected by diseases of the ocular posterior segment including age-related macular degeneration (AMD) (196 million) and diabetic eye disease (146 million) constitute a large proportion [1]
penetration enhancers (PEs) that can efficiently access or facilitate penetration of cargo to the fundus oculi by topical eye drop instillation, and to the best of our knowledge we obtained all-inclusive search results that correspond to our eligibility criteria

Summary

Introduction

Eye diseases originating in the posterior segment ocular tissues, mainly in the retinachoroid, are a major cause of visual impairment across the globe. It is estimated that worldwide, around 2.2 billion people have some sort of visual impairment and out of these, people affected by diseases of the ocular posterior segment including age-related macular degeneration (AMD) (196 million) and diabetic eye disease (146 million) constitute a large proportion [1]. AMD is the reason for 8.7% blindness globally with projected estimates at 196 million people having this disease in 2020 and expanding to 288 million by 2040 and is the single and most widely recognized cause of elderly blindness in developed nations, especially in individuals over 60 years of age [1,2,3]. In the working adult population of the world and in Europe diabetic eye disease comprising diabetic retinopathy (DR) and diabetic macular edema (DME) is the most common reason for vision impairment and blindness, with a prevalence of approximately

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