Ocular Drug Delivery Nanowafer with Enhanced Therapeutic Efficacy

Abstract

Presently, eye injuries are treated by topical eye drop therapy. Because of the ocular surface barriers, topical eye drops must be applied several times in a day, causing side effects such as glaucoma, cataract, and poor patient compliance. This article presents the development of a nanowafer drug delivery system in which the polymer and the drug work synergistically to elicit an enhanced therapeutic efficacy with negligible adverse immune responses. The nanowafer is a small transparent circular disc that contains arrays of drug-loaded nanoreservoirs. The slow drug release from the nanowafer increases the drug residence time on the ocular surface and its subsequent absorption into the surrounding ocular tissue. At the end of the stipulated period of drug release, the nanowafer will dissolve and fade away. The in vivo efficacy of the axitinib-loaded nanowafer was demonstrated in treating corneal neovascularization (CNV) in a murine ocular burn model. The laser scanning confocal imaging and RT-PCR study revealed that once a day administered axitinib nanowafer was therapeutically twice as effective, compared to axitinib delivered twice a day by topical eye drop therapy. The axitinib nanowafer is nontoxic and did not affect the wound healing and epithelial recovery of the ocular burn induced corneas. These results confirmed that drug release from the axitinib nanowafer is more effective in inhibiting CNV compared to the topical eye drop treatment even at a lower dosing frequency.

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“…Rabbit animal model experiments on rapamycin nanomicellar eye drops revealed a noticeably higher concentration of the drug in the retina. These studies demonstrated that nanomicellar formulation enabled drug delivery to the posterior segment with topical eye drop formulation [11].…”

“…Eye drops, although being non-invasive, have shown to have poor drug retention time. It is reported that ≤5% of drug in solution form is absorbed when administered topically [11], therefore the augmentation of this retention time has been widely explored. The lack of bioavailability in the ocular therapeutic treatments is and has been a cause of large concern in the ield of ophthalmology.…”

“…The primary cause of this absence has been found to be due to ef lux transporters. Ef lux transporters were found to be primary barriers leading to poor drug absorption and bioavailability, primarily for anterior segment ocular drug delivery [11].…”

“…For examples, calcium phosphate (CaP) nano-particles have shown great applications in drug delivery systems due to biocompatibility (non-toxic degradation products constitute the inorganic part of human hard tissue). As inorganic CaP nano-particles were found to be chemically stable, they were found to ensure the maintenance of desired pharmacological action [11].…”

Dexamethasone nanowafer as an effective therapy for dry eye disease

“…The nanowafers were fabricated according to a previously published procedure with slight modifications [34][35][36]. A clear CMC solution (4% w/v, 12 mL) was transferred with a pipette onto a polydimethylsiloxane (PDMS) imprint (3″ diameter) containing square posts (of 500 nm × 500 nm, 500 nm high) placed on a flat glass plate and left to dry at room temperature.…”