Table 2.
Advanced DDS for neuroprotection.
| DDS | Drug | Advantages and Considerations | Administration Route | Stage | Reference |
|---|---|---|---|---|---|
| Nanoparticles | |||||
| PEGylated Nanoparticles | Memantine | -Reduced RGC loss -Twice daily administration -Improved drug tolerability |
Topical | Preclinical: ex vivo, in vitro, in vivo | [127] |
| Gemini (PGL) Nanoparticles | Peptide-modified Gemini surfactants | -Non-invasive gene delivery system -Inhibited Aβ40 aggregation -Further studies on ocular in vivo models required |
Topical/ Intravitreal injection | Preclinical: in vitro and in-silico | [128,129] |
| Polydopamine nanoparticles | Brimonidine | -Removed ROS, Promoted RGC survival, suppressed retinal inflammation -Enhanced permeability and retention |
Intravitreal injection | Preclinical: in vitro and in vivo | [114] |
| Nanoparticles | Oncostatin M and Ciliary Neurotrophic Factor | -Sustained delivery -RGC protection -NP aggregation around injection site |
[115] | ||
| PEG-PSA Nanoparticles | Brinzolamide and miRNA-124 | -Prevent RGC damage and IOP-lowering effect -Sustained release, non-toxic -Mechanistic studies further required |
[131] | ||
| Magnetic Nanoparticles | Neurotrophic factors (NGF, BDNF) | -Prevented RGC loss with lower dosage -Sustained, targeted release -Zebrafish model, difficulty in clinical translation |
[117] | ||
| Micelle (PAMAM–PVL–PEG) Nanoparticles | DHEA and S1R agonist | -Novel nanoplatform -Effective RGC protection with targeted delivery -Needs further development for more efficient release and entrapment |
[132] | ||
| Chitosan-Hyaluronic acid CS/HA nanoparticles | Epoetin Beta (EPOβ) | -Increased bioavailability -No local or systemic adverse side effects -Further therapeutic efficacy for neuroprotection in glaucoma model required |
Subconjunctival injection | Preclinical: in vivo | [133] |
| Microspheres | |||||
| PLGA Microspheres | Dexamethasone and Melatonin/ CoenzymeQ10 | -Reduced RGC loss -Multitherapy reduced retinal stress of single doses -Good tolerance |
Intravitreal injection | Preclinical: in vitro, in vivo | [118,119,120] |
| GDNF/Vit E | -Sustained controlled release for up to 6 months -Effective neuroprotection -Optimal dosage not quantified |
||||
| Gel-based polymers | |||||
| Benzoic-acid derivative-modified Chitosan thermogel | Pilocarpine/RGFP966 | -Sustained, controlled drug release -Antioxidant, anti-inflammation properties prevent neurodegeneration |
Intracameral injection | Preclinical: in vitro and in vivo | [122,123] |
| Dendrimer in thermogel | Pilocarpine/Ascorbic acid | ||||
| Nanoparticle-laden hydrogel | CBGA (Cannabigerolic acid) | -Improves bioavailability of drug -Reduced irritancy, improved permeation -Therapeutic efficacy with in vivo models required |
Topical | Preclinical: in vitro | [124] |
| Other | |||||
| Solid Lipid Nanoparticles | Δ9-Tetrahydrocannabinol-valine-hemisuccinate | -Neuroprotective and also lowers IOP -Prolonged residence time -Further cytotoxicity profiling required |
Topical | Preclinical: in vitro and in vivo | [125,126] |
| Microcrystals | Sunitinib | -Prevents RGC death -Therapeutically relevant concentrations obtained -Sustained release |
Subconjunctival injection | Preclinical: in vivo | [134] |
| Cubosomes | LM22A-4 (Neurotrophic factor) | -Prevented RGC loss and improved functional outcomes -Gradual targeted release |
Intravitreal injection | Preclinical: in vitro and in vivo | [121] |
| LAPONITE synthetic clay | Brimonidine | -Sustained delivery (up to 6 months) -Delayed neuroprotection and IOP lowering -Brimonidine depressant side effects on CNS, pharmacodynamic adjustment required |
Intravitreal injection | Preclinical in vivo | [116] |