Table 2 Clinical applications of polymeric nanoparticles in the eye
From: Distribution of polymeric nanoparticles in the eye: implications in ocular disease therapy
Disease | Animal model | Polymer, Drug | Size (nm), Zeta potential (mV) | Route | Drug efficacy | Clearance | Toxicity | Ref |
|---|---|---|---|---|---|---|---|---|
Corneal allograft rejection | Rat | PLGA, Dexamethasone sodium phosphate | 200 ± 8, − 8 ± 1.4 | Subconjunctival injection | Prevented corneal edema and opacification. Significantly reduced neovascularization | 65% retained in conjunctiva after 2 d and 5% after 7 d | Mild inflammation at injection site. No corneal inflammation | [23] |
Mouse | PLGA-RGD peptide, Flt23k plasmid | 270.2 | Subconjunctival injection | Significantly reduced neovascularization and increased graft survival by 20% alone. Combined with triamcinolone, graft survival was increased to 91.6% | NA | NA | [24] | |
Glaucoma | Rabbit | Hyaluronic acid-modified chitosan, dorzolamide hydrochloride and timolol maleate | 319.5 ± 4, 33.3 ± 6.1 | Topical | Significantly reduced IOP more than marketed free drug formulation with longer sustained effect | NA | No ocular irritation detected up to 24 h | [33] |
Uveitis | Rabbit | Poly beta-amino ester, triamcinolone acetonide | 178 ± 6, 5.3 ± 1.7 | Topical | Topically applied nanoparticles reduced inflammation to the same degree as subconjunctivally injected free drug | NA | NA | [35] |
Autoimmune Uveitis | Rat | PLGA, zinc, Dexamethasone sodium phosphate | 210 ± 15, − 9 ± 2 | Subconjunctival injection | Reduced clinical disease score, inflammatory cytokine expression, and microglia activation, and improved ERG response compared to free drug | Dexamethasone sodium phosphate, detectable for 21 d post injection | No changes in retinal function or ocular histology due to nanoparticle injection | [36] |
Autoimmune Uveoretinitis | Rat | PEG-PLGA, betamethasone | 120 | Intravenous injection | Reduced inflammatory symptoms up to 14 d | NA | NA | [34] |
Selenite Cataract | Rat | PLGA or Zein, lutein | 222.9 ± 1.2, − 32.4 ± 3.9 | Topical and Oral | Topically applied PLGA and zein nanoparticles loaded with lutein significantly decreased cataract score compared to control, free lutein, and orally administered lutein or lutein loaded nanoparticles | NA | NA | [45] |
Posterior lens opacification | Rabbit | Chitosan, 5-fluorouracil |  < 400 nm (most < 100 nm) | Loaded into intraocular lens prior to transplantation | nanoparticles significantly decreased proliferation of lens epithelial cells, increased apoptosis, and reduced necrosis compared to free drug loaded lens implants | Burst release for 10 h, followed by sustained released for 100 h | Significantly reduced inflammation and immune cell infiltration compared to free drug loaded lens implants | [46] |
Brucellosis | 46 | Mannosylated-poly(anhydride), hot saline antigen complex | 306 ± 11, − 34.6 ± 1.3 | Subconjunctival injection | nanoparticle group had twofold higher fecal IgA excretion and significant reduction in spleen CFU compared to standard Rev1 vaccine | NA | No toxicity observed in cornea or iris but hyperemic blood vessels and redness occurred in some eyes | [51] |
Choroidal neovascularization | Rat | PLA/PLA-PEO, C16Y integrin antagonist peptide | 302.5 ± 85.1, − 38.26 ± 1 .42 | Intravitreal injection | Prolonged anti-angiogenic effect longer than free drug (at least 12 d) | NA | No acute inflammatory response | [56] |
Mouse | PLGA microparticles, Serpin-derived peptide | 6000 | Intravitreal injection | Prolonged anti-angiogenic activity longer than free drug (up to 14Â weeks) | NA | NA | [57] | |
Rat | PLGA, shRNA targeting (HIF-1α) | 303.7 ± 3 8.5 | Intravitreal injection | Significantly decreased choidal leakage and thickness of lesions | NA | No changes in histology or retinal function | [58] | |
Diabetic retinopathy | Mouse | CK30PEG10K, miR200b | NA | Intravitreal injection | Decreased expression of VEGR-2 and suppressed angiogenesis for 3Â months post injection | NA | NA | [59] |
Retinal detachment and excitotoxicity | Rat | Poly(γ-glutamic acid)-L-phenylalanine, dexamethasone | 180 ± 45, − 25 | Intravitreal injection | nanoparticles suppressed TNFα and MCP-1 cytokines in cultured macrophages and microglia, reduced microglia activation and death of retinal ganglion cells in excitotoxic animal models, and decreased apoptosis of photoreceptors in retinal detachment animal models | NA | NA | [76] |
Acute retinal photo-injury | Rat | PLGA, connexin43 mimetic peptide | NA | Intravitreal injection | Significantly improved ERG response compared to control and decreased immune cell infiltration, reduced astrocyte and Müller cell activation, and preserved choroidal thickness compared to free drug and control | NA | NA | [77] |
Optic nerve crush | Rat | HSA, brimonidine | 152.86 ± 51.1, − 29. ± 7.5 | Intravitreal injection | Significantly reduced A-β deposition in retinal ganglion cells and increased retinal ganglion cell survival | NA | NA | [78] |