Table 5 The application of nanomaterials in combination with immunosuppressive drugs in the treatment of ocular diseases
From: Next-generation nanomaterials: advancing ocular anti-inflammatory drug therapy
Immunosuppressive drugs | Nanomaterials | Size (nm) | Production method | Cells (in vitro) | Animals (in vivo) | Administration route | Characteristics and effects | Refs. |
|---|---|---|---|---|---|---|---|---|
CsA | PLA-b-Dex-NPs | 26.9–29.1 | Nanoprecipitation method | – | Rabbits and scopolamine-induced dry eye in mice | Eye drops | CsA-loaded PLA-b-Dex-NPs exhibited prolonged retention in the eye, potent anti-inflammatory effects, restoration of ocular surface goblet cells, and reduced dosage and frequency of medication compared to conventional preparation | [243] |
CsA | Compritol 888 ATO, poloxamer 188, and Tween 80-SLNs | 225.9 ± 5.5 | High shear homogenization method | – | Rabbits | Eye drops | CsA-loaded SLNs exhibited high drug concentrations in the aqueous humor, without causing any ocular irritation | [244] |
CsA | Cys-NLCs | 66.9 ± 0.4 | Melt-emulsification method | Cellulose membrane system | Rabbits | Eye drops | CsA-loaded Cys-NLCs exhibited sustained drug release, strong bioadhesion, and elevated AUC0-24 h and MRT0-24 h values in aqueous humor, tear fluid and ocular tissue | [245] |
CsA | INS and MS | 385 | – | – | Rabbits | Eye drops | CsA-loaded INS exhibited minimal eye irritation; CsA-loaded MA exhibited no eye -irritation; CsA-loaded INS and MA exhibited a higher drug concentrations in the cornea compared to commercially available formulations | [246] |
Rapamycin | Vit E TPGS and Oc-40 nanomicelles | 10.84 ± 0.11 | Novel solvent evaporation method | rPCECs and D407 | Rabbits | eye drops | Rapamycin-loaded MNFs exhibited high drug encapsulation efficiency, favorable cell tolerance, elevated drug concentration in the retina-choroid, and no drug residue in the vitreous | [247] |
TAC | NH2-PEG-b-PLA and HPMC nanomicelles | 101.4 ± 1.3 | Solvent-evaporation-induced self-assembly in aqueous solution method | HCECs, isolated corneas of rabbits, and cellulose membrane system | Rabbits and allogeneic penetrating corneal transplantation in rats | Eye drops | TAC-loaded nanomicelles exhibited a high permeability, sustained high concentrations, and prolonged anti-rejection effect in ocular tissues of rat corneal transplantation | [248] |
TAC | mPEG-b-PLGA nanomicelles | 81.3 ± 1.3 | Solvent-evaporation-induced self-assembly in aqueous solution method | HCECs, isolated corneas of rabbits, and cellulose membrane system | Rabbits and Allogeneic penetrating corneal transplantation in rats | Eye drops | TAC-loaded mPEG-b-PLGA nanomicelles exhibited a higher corneal permeability than that of 0.05% tacrolimus eye drops, excellent biological safety, reduced expression of NFAT, CD4, and CD8 in tissues following corneal transplantation, and inhibition of immune rejection | [249] |
TAC | PLGA-NPs | 164– 375 | Emulsification-diffusion method | Isolated corneas of rabbits | Rabbits | Eye drops | TAC-loaded PLGA-NPs exhibited remarkable corneal permeability, excellent stability, superior tissue tolerance, and high drug concentrations in the cornea, conjunctiva, and aqueous humor | [250] |
TAC | Gellan gum NPs | 274.46 ± 8.90 | Improved ionotropic gelation method | Isolated corneas of goats, HET-CAM test, and cellulose membrane system | Rabbits | Eye drops | TAC-loaded gellan gum NPs exhibited high encapsulation efficiency and loading capacity, prolonged drug release, extended residence time in the cornea, and the improved dry eye symptoms | [251] |
TAC | MSNAPTES silica NPs | 103 ±  14.2 | Improved ionotropic gelation method | ARPE- 19 and HET-CAM test | Rats | Intravitreal injections | TAC-loaded MSNAPTES silica NPs exhibited excellent biocompatibility with no observed cytotoxicity. | [252] |
TAC | N-palmitoyl-N-monomethyl-N, N-dimethyl-N, N, and N-trimethyl-6-O-glycol CS-NPs | 200 | Thin-film hydration method | – | Rabbits | Eye drops | TAC-loaded NPs exhibited excellent physical stability, highly permeability, no eye irritation, and high drug concentrations | [253] |
TAC | PLGA, castor oil, Tween ® 80, Cremophor ® EL, and Lipoid®E80 nanocapsules | 106–166 | Solvent displacement method | Isolated corneas of pigs | S-antigen and pertussis toxin-induced EAU in rats, LPS-induced keratitis in mice | eye drops | TAC-loaded nanocapsules exhibited excellent physical stability, high permeability, no eye irritation, inhibition of KC, MIP-2, IL-6 and GCSF expression | [254] |
TAC | Compritol® 888 ATO, GMS, Tween-80, and glycerin SLNs in situ gel | 122.3 ± 4.3 | Probe sonication method | Cellulose membrane system | Rabbits and ovalbumin-induced immune conjunctivitis in mice | Eye drops | TAC-loaded SLNs in situ gel exhibited sustained drug release, inhibition of inflammatory mediators from conjunctival mast cells, and suppression of OVA-specific IgE, IFN-γ and IL-4 | [255] |