Ocular anatomic barriers and routes of drug administration. Ocular barriers to topical administration (iv) of therapeutic agents to the anterior surface of the eye and to the posterior segment are illustrated. These include (A) tear film barrier; (B) corneal barrier; (C) vitreous barrier; (D) blood–retinal barrier and (E) blood–aqueous barrier. Various methods for drug delivery to the eye include; (I) intravitreal injection, (II) subconjuctival injection, (III) subretinal injection and (IV) topical administration. Topical administration of eye drops is one of the non-invasive route of administration and has minimum side effects. Intravitreal injections on the other hand are invasive, can cause retinal damage but can easily bypass all ocular barriers. While subconjuntival and subretinal injections can bypass some of the ocular barriers and are less invasive. (Alqawlaq et al., 2012).

Ocular drug-delivery system using drug-loaded soft contact lenses. (A) Opthalmic drugs delivered though conventional eye drops. Majority of the drug administered gets drained a few minutes after instillation. (B) Drug delivery through molecularly imprinted soft contact lenses. This approach can increase the residence time of the drug molecules on the ocular surface increasing drug bioavailability as compared to conventional eye drop formulations. (Tashakori-Sabzevar F et al. 2015). MIP: molecularly imprinted polymer.

ECT for back of the eye disorders. CAC ECT gel treatment on rats with inherited retinal degeneration. One or two units of GDNF-delivering CAC ECT gel was intravitreally injected into the eyes of dystrophic RCS/lav rats. (A) Representative H&E sections of nontreated, single, and double gel-treated rats showed different degrees of photoreceptor nuclei retention and organization in the outer nuclear layer (ONL). (B) ONL nuclei density was calculated by normalizing ONL count with retinal length. (C) Representative images showing the distribution of apoptotic cells (green) in the retina of nontreated, single, and double gel-treated animals detected by terminal deoxynucleotidyl transferase–mediated digoxigenin-deoxyuridine nick-end labeling (TUNEL) assay with 4’,6-diamidino-2-phenylindole (DAPI) nuclear counterstaining. (D) Density of apoptotic cells in the ONL. (E) Representative scotopic and photopic electroretinogram wave forms showing the retinal function of dystrophic rats receiving 1 or 2 U of GDNF-secreting gel. (F) Scotopic a-wave. (G) Scotopic b-wave. (H) Photopic b-wave. #P < 0.05; *P ≤ 0.02; **P ≤ 0.005; ***P < 0.0005 by one-way ANOVA with Bonferroni post hoc test (Wong et al., 2019). ERG, electroretinogram; INL, inner nuclear layer.

TA-encapsulated methoxy PEG (mPEG)–PLGA nanoparticles for treating experimental autoimmune uveitis (EAU). (A–D) photographs taken by a hand-held retinal camera on day 12 after treatments: the EAU group (A), the mPEG-PLGA nanoparticle–treated group (B), the TA injection–treated group (C), the TA-loaded mPEG-PLGA nanoparticle–treated group (D), and clinical scores in the different groups (E).

In vivo efficacy of PLGA fenofibrate NPs (Feno-NP) on vascular leakage and vascular permeability measured with Fundus Fluorescein Angiography (FFA). Formation of subretinal neovascularization (SRNV) and intraretinal neovascularization (IRNV) evaluated by neovascular tufts in flat-mounted choroid and retina in Vldlr−/− mice 1 month after Feno-NP treatment. (A) Representative images of FFA. (B) Numbers of leakage spots in FFA. (C) Quantification of retinal vascular permeability. (D) Representative images of SRNV and IRNV in FFA. Scale bar, 1000 μm. (E) Quantification of SRNV and IRNV in flat-mounted choroid and retina. Mean ± S.E.M. (n = 8–16; one-way ANOVA followed by Bonferroni post hoc test). ***P < 0.001 vs. untreated Vldlr−/− mice; ###P < 0.001 vs. blank-NP–treated Vldlr−/− mice (Qiu et al., 2019).

Microneedles for enhanced drug delivery to the cornea. Drug-loaded, DC101, and diclofenac microneedle (DL-MN) patch for synergistic effect. Mouse eyes were treated 2 days after being inflicted with alkali burn and examined on day 7. (A) Illustration of drug loadings in DL-MNs and representative images of differently treated eyes. (B) Quantifications of corneal neovascularization. The white dotted lines indicate the extent of neovascular outgrowth from the limbus. Statistical comparison between groups was performed using one-way ANOVA. *P < 0.05; **P < 0.01 vs. control; #P < 0.05; ##P < 0.01 between indicated pairs (Than et al., 2018). Diclo, Diclofenac; ED, eye drop; HA, hyaluronic acid; MeHA, methacrylated hyaluronic acid.