Table 4.
Nanocarriers to Deliver Anti-Age-Related Macular Degeneration Agents
| Study | Experimental Models | Drug | Vehicle/Carriers | Production Method(s) | Results | Conclusion | Future Direction |
|---|---|---|---|---|---|---|---|
| Tang M, et al178 2018 | An Alkali-Burn Corneal Neovascularization Model in the Mouse | Silicon | Nanoparticles | Photochemical method. | SiNPs-RGD features efficacious antiangiogenic ability; SiNPs-RGD can label angiogenic blood vessels and has neovascularization suppression effects. | the SiNPs-RGD as a novel class of high-quality theranostic probe is suitable for simultaneous diagnosis and treatment in ocular neovascular diseases | Unspecified |
| Wang Y, et al116 2016 | Balb/c mice and Sprague-Dawley rats | LPD-mediated gene delivery | Lipid-based nanoparticles | A two-step packaging technology employing a multilayering method | Cell-specific promoters enable lipid-based nanoparticles to deliver genes to specific retinal cells in vivo. | This work will inspire investigators in the field of lipid nanotechnology to couple cell-specific promoters to drive expression in a cell- and tissue-specific manner. | The formulated lipid nanoparticles may be appropriate for use with other tissues for the purposes of gene delivery with tissue-specific promoters. |
| Huu VA, et al179 2015 | Sprague-Dawley rats | Nintedanib | Nanoparticle | Light-sensitive polymer | Stably retain encapsulated molecules in the vitreous; released cargo in response to UV exposure up to 30 weeks post-injection; light-triggered release of nintedanib 10 weeks post-injection suppresses CNV in vivo. | Light-sensitive nanoparticles are biocompatible and cause no adverse effects on the eye as assessed by electroretinograms (ERG), corneal and retinal tomography, and histology. | Whether light can trigger release of multiple therapeutic doses of BIBF1120. |
| Luo L, et al180 2013 | C57BL/6J mice and Cynomolgus macaque monkeys | RGD- targeted | PLGA nanoparticles | Emulsion solvent evaporation method | Improved with nearly 40% restoration of visual loss induced by CNV. | These findings offer a nanoparticle-based platform for targeted, vitreous-sparing, extended-release, nonviral gene therapy. | Further studies would be necessary before concluding this delivery system is completely safe. |
| Iwase T, et al181 2013 | Pathogen-free C57BL/6 mice and Dutch belted rabbits | Doxorubicin | Poly(sebacic acid)–polyethylene glycol nanoparticles | Oil-in-water emulsion method | Reduced HIF-1-responsive gene products, strongly suppressed CNV, and no retinal toxicity; suppressed NV for at least 35 days in vivo; sustained release in vivo for at least 105 days. | A novel HIF-1-inhibitor-polymer conjugate formulated into controlled-release particles maximizes efficacy and duration of activity, minimizes toxicity, and provides a promising new chemical entity for treatment of ocular NV. | A single-agent that targets multiple pro-angiogenic effectors is expected to have substantial benefits from a clinical perspective and could provide a major step forward the treatment of highly prevalent neovascular diseases of the eye. |
| Kyosseva SV, et al182 2013 | Mutant mice with targeted deletion of the Vldlr gene | Cerium oxide | Nanoparticles | Simple wet chemistry methods | Many cell signaling, cellular development, growth and proliferation, and tissue development were affected; inhibited the activation of ERK 1/2, JNK, p38 MAP kinase, and Akt. | Nanoceria may represent a novel therapeutic strategy to treat AMD, RAP, and other neurodegenerative diseases. | Unspecified |
| Yandrapu SK, et al183 2013 | Rat model | Bevacizumab | PLGA nanoparticles | Emulsion solvent evaporation method | In vitro release of bevacizumab from NP in PMP was sustained for 4 months. | NP in PMP is a novel sustained release system for protein drugs to reduce frequency of protein injections in the therapy of back of the eye diseases. | NPinPMP will sustain drug levels much further in vivo, which will be assessed in future studies. |
| Jo DH, et al184 2012 | C57BL/6 mice | Silicate | Nanoparticles | Reverse microemulsion method | No direct toxicity; reduced anomalous retinal angiogenesis in vivo; inhibited in vitro VEGF-induced angiogenesis via suppression of VEGF receptor-2 phosphorylation and blocking ERK 1/2 activation. | SiNPs could be an inhibitor of the potency and safety of retinal neovascularization that is mediated by VEGF | Biodegradation and biodistribution of NPs might be investigated before clinical application |
| Iezzi R, et al185 2012 | Royal College of Surgeons (RCS) rat retinal degeneration model | Hydroxyl-terminated polyamidoamine | Nanodevices | Unspecified | Sustained release effects over 90 days. One intravitreal injection of 1 mg of FA conjugated to 7 mg of the dendrimer was able to arrest retinal degeneration, preserve photoreceptor outer nuclear cell counts, and attenuate activated microglia, for an entire month. | PAMAM dendrimers (with no targeting ligands) have an intrinsic ability to selectively localize in activated microglia, and can deliver drugs inside these cells for a sustained period for the treatment of retinal neuro-inflammation. | This approach can have significant implications in the treatment of neuro-inflammation in other neurodegenerative diseases such as cerebral palsy, autism, and Alzheimer’s disease. |
| Liu HA, et al186 2011 | Brown-Norway rats | PEGylated liposome-protamine-hyaluronic acid nanoparticles (PEG-LPH-NP) loaded with siRNA (PEG-LPH-NP-S) | Liposome-polymer hybrid nanoparticles | Post-insertion method | Protected siRNA load and facilitated the intracellular delivery of siRNA, the expression inhibition of VEGFR1, and the reduction of CNV area in vivo. | PEG-LPH-NP may be a promising lipid nanoparticle system for the siRNA treatment of CNV. | Unspecified |
| Jin J, et al119 2011 | Brown Norway rats | Plasminogen kringle | PLGA nanoparticle | Emulsion–diffusion–evaporation technique with some modifications | Intense K5 expression was detected in the retina 2 weeks after the injection of K5-NP. Areas of CNV were significantly decreased in the K5-NP treatment group compared with that in the control-NP group. The K5-NP injection also significantly reduced vascular permeability. | K5 has a novel anti-inflammatory activity. K5-NP mediates a sustained inhibitory effect on CNV | The receptor and signaling pathway mediating the anti-inflammatory activity of K5, however, remains to be defined. |
| Zhang C, et al187 2010 | Brown Norway rats | PshHIF-1α | PLGA nanoparticle | Water-in-oil-in-water (W/O/W) multiple emulsion technique | Expression of GFP preferentially localized in the retinal pigment epithelium cell layer and lasted for 4 weeks; reduced the mean thickness of the CNV lesions in vivo. | pshHIF-1α NPs may act as a novel therapeutic option to transfer specific pDNA and inhibit the formation of experimental CNV. | The efficacy of this method is not clear yet and needs further determination. |
Abbreviations: IOP, intraocular pressure; AMD, age-related macular degeneration; RAP, retinal angiomatous proliferation; CNV, choroidal neovascularization.