Promising therapeutic drug delivery systems for glaucoma: a comprehensive review

Abstract

The delivery of ophthalmic drugs is challenging despite easy accessibility via the ocular surface. Topical instillation of eye drops is a relatively easy and most commonly used as a conduit for drug delivery for treating a myriad of ocular morbidities, particularly involving the anterior segment, and has an additional benefit of avoiding the first-pass metabolism while passing through the systemic circulation. The primary challenges of drug administration through traditional methods include—inadequate patient education for proper drug instillation technique, compliance, adherence, and persistence. Various dynamic (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution) and static (namely, different layers of cornea, sclera, and retina including blood aqueous and blood–retinal barriers) ocular barriers limit drug delivery to the target ocular tissues. The maintenance of the therapeutic drug levels on the ocular surface for a prolonged duration is an added challenge, thus preventing persistent delivery for longer durations. These factors result in inadequate management, leading to poor prognosis in vision loss in as many as 27% of the patients diagnosed with glaucoma. We have reviewed the research and advancements in the development of novel and well-tolerated drug delivery systems with the common goal of overcoming the factors limiting adequate drug delivery to the target tissues in glaucomatous patients with traditional techniques. In the recent past, multiple research groups have successfully designed noninvasive, sustained drug delivery systems, promoting the efficacy as well as the feasibility of delivering topical drugs to the anterior segment.

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“…Furthermore, glaucoma is recognized as the second cause of blindness, in developed countries, and its management requires lowering IOP by enhancing the drainage of fluid from the eye or decreasing the generation of the fluid. Different classes of drugs can be used to lower IOP: β-blockers, adrenergic agonists, carbonic anhydrase inhibitors, prostaglandin analogues, miotics, and hyperosmotic drugs [ 22 , 23 , 24 ]. Each of these categories of drugs presents inherent adverse effects, which leads to the search for more effective and safer alternatives.…”

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“…Pilocarpine is incorporated into a core of alginate gel, which is a central reservoir surrounded by a microporous membrane of ethylene-vinyl acetate copolymer. Pilocarpine diffuses in a controlled manner through this membrane [ 206 , 207 ]. Ocusert ® is withdrawn from the market because of burst drug release and dislocation problems [ 202 ].…”

“…Soft CLs are a network formed after the cross-linking of water-soluble polymeric hydrogels. Numerous polymers have been used in their formulations [ 202 , 207 , 226 ].…”

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“…Compared with standard medical therapy, drug delivery systems have the potential to improve patient adherence, reduce side effects, increase efficacy, and ultimately, preserve sight of glaucoma patients. 101 , 102 Among these treatments, the injectable systems have produced good results in the recent past. Injectable systems are passive delivery systems, capable of delivering medications to the target tissues for an extended period.…”