Ocular novel drug delivery: impacts of membranes and barriers

Abstract

Background : Ocular drug delivery is an extremely challenging area due to its restrictive barrier functionalities. Objective : Drug transport via corneal/non-corneal routes involves several intricate biological processes such as drug penetration across the ocular barriers and transfer to the anterior or posterior chambers, thus the influence of these processes on the pharmacotherapy of the eye should be fully addressed. Methods : To pursue the impacts of such impediments in novel drug therapy, recent publications were reviewed regarding advanced strategies such as nanomedicines. Conclusion : The ocular barriers are highly specialized and selectively control the inward/outward traverse of compounds, hence a better understanding of these biological obstacles would provide a platform to advance ophthalmic drug therapy towards specified delivery/targeting with minimal adverse consequences.

Functional intercalated nanocomposites with chitosan-glutathione-glycylsarcosine and layered double hydroxides for topical ocular drug delivery

“…CG-GS-FITC-LDH nanocomposites were coincubated with sodium azide for 4 h, and the fluorescence internalized into the cells was significantly reduced (P,0.001), implying an energy-dependent process was involved in the transport ( Figure S6). Meanwhile, a significant reduction of transport was observed in the presence of hypertonic sucrose (P,0.001) and chlorpromazine (P,0.05), proving a clathrin-mediated endocytosis pathway, which is consistent with our previous work and work by Oh et al 45 To further elucidate the specific interaction of CG-GS-LDH nanocomposites with PepT-1 expressed on the HCEpiC, 10,46 competitive binding experiments were performed by pretreating cells with free GS solution to block PepT-1 prior to incubating with different DS of GS in CG-GS-LDH (Figure 6). 47 All GS with the concentration of 1, 5 …”

Corticosteroids and Anti-Complement Therapy in Retinal Diseases

“…Even though systemic administration might be useful in treating posterior segment eye diseases, high doses and frequent dosing may be required since there are various limitations including extensive drug dilution in the blood, low cardiac output to the eye, and bloodocular barriers that restrict drug permeability. Furthermore, drugs administered by the systemic route are subjected to metabolism by the liver and clearance by the kidney, resulting in only a small quantity of the drug typically reaching the vitreous humor (Furrer et al 2009;Duvvuri et al 2003;Barar et al 2008). High drug doses and frequent administrations usually result in systemic side effects.…”

Liposomes and nanotechnology in drug development: focus on ocular targets

“…As a result, less than 5% of the drug can cross the corneal barrier and gain access to the inner eye. [6][7][8] In contrast, although systemically administered drugs can reach the choroid membrane, drug delivery into the retina or the vitreous body is difficult to achieve through conventional methods because of the presence of the blood-aqueous barrier and the inner and outer bloodretinal barriers in those structures. 9 As a result, large doses are often required, which leads to concern over systemic side effects.…”