Table 2.

Clinical applications of polymeric nanoparticles in the eye

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 14 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 3 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]