Table 3.

Biodegradable nano-based DDS for uveitis.

Disease	Drug	DDS	Advantages and Considerations	Administration Route	Stage	Reference
EAU	Cyclosporin A	mPEGhexPLA nanocarriers	Well tolerated locally. No immediate toxicity after repeated application. Applied noninvasively as eye drops. Versatile: nanocarrier suitable for topical/systemic application. Known to deliver other drugs.	Topical	Preclinical mouse models in vitro and in vivo.	[8]
EAU	Tacrolimus	PLGA nanocapsule	Homogeneous size. High encapsulation efficiency. No eye irritation after multiple applications.	Topical	Preclinical rabbit models ex vivo and in vivo.	[9]
EAU	Adalimumab	Low-deacetylated chitosan and β-glycerophosphate hydrogel	No significant adverse effects. Higher drug release. Amounts within limited time. Excellent therapeutic efficacy.	Topical	Preclinical rat models in vitro and in vitro.	[10]
EAU	Dexamethasone sodium phosphate	Carboxyl-terminated PLGA with DSP-Zn-NP	Improved loading and sustained release of dexamethasone. Reduced inflammatory cell infiltration. Preserved retinal function. No retinal toxicity.	Subconjunctival injection	Preclinic rat models ex vivo and in vivo.	[11]
EAU	Triamcinolone acetonide	mPEG-PLGA nanoparticles	Could sustain for more than 45 days. Good biocompatibility. High entrapment rate and good controlled-release profile in vitro.	IVT	Preclinical rat models in vitro and in vitro.	[12]
Non-EAU, EIU	Succinated triamcinolone acetonide (TA-SA)	Supramolecular hydrogel with PECE nanoparticles.	Decreases neutrophil infiltration in anterior chamber. No noticeable side effects.	Topical	Preclinical rabbit models in vitro and in vitro.	[13]
Non-EAU, EIU	Triamcinolone acetonide	PLGA-chitosan nanoparticles.	Controlled drug release for 100 h. Excellent anti-inflammatory activity. Significantly reduced the secretion of IL-6.	Subconjunctival injection	Preclinical rabbit models in vitro and in vitro.	[14]
EAU	Rapamycin	EVs derived from mesenchymal stem cells (MSC-sEVs).	Excellent biocompatibility. Limited drug release kinetics and toxicity data.	Subconjunctival injection	Preclinical mouse models in vitro and in vivo.	[15]
Non-EAU, EIU	Tacrolimus	PNV	Prevented breakdown of the blood aqueous barrier. Sustained release of Tacrolimus for 12 h.	Topical	Preclinical rabbit models in vitro and in vivo.	[16]
Non-EAU, EIU, Anterior uveitis	Beclomethasone Dipropionate	Cubosomes and Cubosomal Gels	Significant controlled release. Enhanced corneal permeability. Greater relative bioavailability. Great encapsulation efficiency. High ocular tolerability.	Topical	Preclinical rabbit models in vitro and in vivo.	[17]
EAU	Copper–zinc superoxide dismutase (SOD1)	Multilayer polyion complex nanoparticles of SOD1	Penetrates interior eye structures more effectively than SOD itself. Retains enzyme activity in the eye longer. Restores antioxidant activity in the eye.	Topical	Preclinical rabbit models in vitro and in vivo.	[18]
EAU	Dexamethasone	Dexamethasone sodium phosphate supramolecular hydrogel composed of Dex and calcium ion	Well tolerated without complications of fundus blood vessel tortuosity or lens opacity. Downregulation of Th1 and Th17.	IVT injection	Preclinical rat models in vitro and in vivo.	[19]
Non-EAU, Carrageenan-induced	Triamcinolone acetonide	PEG-b-PCL and PEG-b-PLA micelles	High drug loading and drug encapsulation efficiencies. Hydrogel slowed the drug release rate (42% of drugs released in one week compared vs. ∼95%).	Topical	Preclinical rabbit models in vitro and in vivo.	[20]
EAU	Prednisolone	SMEDDS	Stable and sustained drug release. No irritation.	Topical	Preclinical rabbit models in vitro and in vivo	[21]
Non-EAU, EIU, Anterior uveitis	Ibuprofen	Hydrogel	Good cytocompatibility. Excellent ocular biocompatibility when instilled topically. Therapeutic efficacy comparable to current treatment.	Topical	Preclinical rabbit models in vitro and in vivo	[22]
EAU	Sirolimus (SRL)	Implant	Safe. Reduced inflammation.	Topical	Preclinical rabbit model in vivo	[23]
Non-EAU, EIU	Cyclosporin	In situ gel (PolyGel™) PCBCL-b-PEG-b-PCBCL	CyA’s t1/2 is 87% longer compared to Restasis®. Showed comparable profile to Restasis.	Topical	Preclinical rabbit model in vivo	[24]
Non-EAU, Anterior uveitis	Prednisolone phosphate and triamcinolone acetonide phosphate	PEG-liposomal formulation	Effective and sustained anti-inflammatory action (superior to eye drops). Little risk of globe injury compared to peribulbar injections. No intraocular penetration. No risk of endophthalmitis. Not powered to study adverse effects.	Subconjunctival injection	Preclinical rabbit model in vivo	[25]
Non-EAU, Anterior uveitis	Triamcinolone acetonide	Cationic nanostructured lipid carriers	Enhanced ocular bioavailability. No cytotoxicity and non-irritant. Could be retained inside cells for 24 h. Efficacious in uveitis treatment at a much lower concentration (0.1%) of drug.	Topical	Preclinical goat models ex vivo and in vitro	[26]
Non-EAU, EIU, Anterior uveitis	Dexamethasone	PCL-PEG-PCL micelles	More trials are needed. More prolonged follow-ups are needed. At 24 and 36 h PCL-PEG-PCL displayed a better inhibitory effect than market eye drops, but not significantly.	Topical	Preclinical rabbit models in vitro and in vivo	[27]
Non-EAU, EIU, Anterior uveitis	Flurbiprofen	Polypseudorotaxane hydrogels with Soluplus micelles	Excellent biocompatibility and ocular tolerance. Significantly suppressed intraocular inflammation at reduced administration frequency.	Topical	Preclinical rabbit models in vitro and in vivo	[28]
Non-EAU, EIU, Anterior uveitis	Dexamethasone	Nanoparticle	Good ocular tolerance. No changes in corneal thickness or intraocular pressure. Low cytotoxicity in human corneal epithelial cells at drug concentrations up to 1 mM after 24 h. Reduced cell viability after 48 h and 72 h.	Topical	Preclinical rabbit models in vitro and in vivo	[29]
Non-EAU, Posterior uveitis	Everolimus	Soluplus®: grafted copolymer of PVCL–PVA–PEG nanomicelles	High encapsulation efficiency. Sustained release of everolimus. Remained in the circulatory system for a longer duration. Significantly higher permeation across goat cornea. Improved drug bioavailability and accessibility.	Topical	Preclinical models ex vivo and in vitro	[31]
EAU, Posterior uveitis	Triamcinolone acetonide	Glycosylated triamcinolone acetonide hydrogelator hydrogel	Downregulated Th1 and Th17 responses. No cytotoxicity on ARPE-19 or RAW264.7 cells up to 600 uM. Toxic effects from TA suspension at 69 nmol/per eye.	IVT injection	Preclinical rat animal model in vivo	[30]
EAU, Posterior uveitis	Rapamycin	MET-RAP nanoparticle eyedrops	Activity like dexamethasone eye drops. Reduced RORγt and increased Foxp3 expression in IL-10.	Topical	Preclinical mouse and rabbit models in vitro and in vivo	[32]
Non-EAU, Endophthalmitis	Gatifloxacin	Nanosponge	Decreased ocular pathology and inflammation. Lack of toxicity. In vivo stability.	IVT injection	Preclinical murine and rabbit models in vitro and in vivo	[34]
Non-EAU, Endophthalmitis	Azithromycin or triamcinolone acetonide	Nanoparticle	Sustained release of drug for 300 h. Exhibited antimicrobial effects against Gram-positive and Gram-negative bacteria. Synergistic effects.	Topical	Preclinical mouse models in vitro and in vivo	[36]
Non-EAU, Postoperative uveitis	Curcumin	Double-headed polyester NPs with PLGA-GA2-CUR	Similar protection as with carprofen. Increased oral bioavailability of curcumin.	Oral	Preclinical adult male beagle model	[37]
Non-EAU, Postoperative endophthalmitis	Levofloxacin	Thermosensitive chitosan-based hydrogel	Displayed sustained-release profile. Long-term antibacterial property.	Cell culture assay	Preclinical rabbit epithelial cells in vitro	[38]
Non-EAU, Postoperative endophthalmitis	Predisolone acetate and levofloxacin	Chitosan-gelatin-based hydrogel containing NPs	Themosensitive and biocompatibility. Sustain drug-release properties.	Topical	Preclinical rabbit models in vitro and ex vivo	[39]
Non-EAU, Postoperative endophthalmitis	Bromfenac sodium (anti-inflammatory drug)	AuAgCu2O-BS NPs	Superior biocompatibility with low cytotoxicity. Metal ions could eliminate MDR bacteria (MRSA) effectively in vitro/vivo. Controlled the thermal damage to the surrounding ocular structure. Did not influence intraocular pressure; no significant toxicity.	Ocular injection	Preclinical rabbit model in vivo	[40]

AuAgCu₂O-BS NPs: AuAgCu₂O-bromfenac sodium nanoparticles. DSP-Zn-NP: Divalent zinc ion nanoparticle. EAU: Experimental autoimmune uveitis. EIU: Endotoxin induced uveitis. MET-RAP: Molecular Envelop Technology (N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan)—Rapamycin. mPEGhexPLA: Methoxy-poly(ethylene-glycol)-hexyl substituted poly-lactic acid. mPEG-PLGA: methoxypoly(ethyleneglycol)-poly(dl-lactideco-glycolic acid). NP: nanoparticle. PCBCL-b-PEG-b-PCBCL: poly(α-carboxylate-co-α-benzylcarboxylate-ε-caprolactone)-block-poly(ethylene glycol)-block-poly(α-carboxylate-co-α-benzylcarboxylate-ε-caprolactone). PCL-PEG-PCL: polycaprolactone-polyethylene glycol-polycaprolactone. PECE: poly (ethylene glycol)-poly (ɛ-caprolactone)-poly (ethylene glycol). PEG-b-PCL: poly(ethylene glycol)-block-poly(ε-caprolactone). PEG-b-PLA: poly(ethylene glycol)-block-poly(lactic acid). PLGA: Poly(lactide-co-glycolide). PLGA-GA2-CUR: gambogic acid—coupled polylactide-co-glycolide—curcumin. PNV: Proglycosome nanovesicles. PVCL–PVA–PEG: polyvinyl caprolactam– polyvinyl alcohol–polyethylene glicol. SMEDDS: self-microemulsifying drug delivery systems.