Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Filters applied. Clear all
. 2018 Sep 11;6(3):92.
doi: 10.3390/biomedicines6030092.

Aflibercept Nanoformulation Inhibits VEGF Expression in Ocular In Vitro Model: A Preliminary Report

Affiliations
Free PMC article

Aflibercept Nanoformulation Inhibits VEGF Expression in Ocular In Vitro Model: A Preliminary Report

Shannon J Kelly et al. Biomedicines. .
Free PMC article

Abstract

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the United States, affecting approximately 11 million patients. AMD is caused primarily by an upregulation of vascular endothelial growth factor (VEGF). In recent years, aflibercept injections have been used to combat VEGF. However, this treatment requires frequent intravitreal injections, leading to low patient compliance and several adverse side effects including scarring, increased intraocular pressure, and retinal detachment. Polymeric nanoparticles have demonstrated the ability to deliver a sustained release of drug, thereby reducing the necessary injection frequency. Aflibercept (AFL) was encapsulated in poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) via double emulsion diffusion. Scanning electron microscopy showed the NPs were spherical and dynamic light scattering demonstrated that they were uniformly distributed (PDI < 1). The encapsulation efficiency and drug loading were 75.76% and 7.76% respectively. In vitro release studies showed a sustained release of drug; 75% of drug was released by the NPs in seven days compared to the full payload released in 24 h by the AFL solution. Future ocular in vivo studies are needed to confirm the biological effects of the NPs. Preliminary studies of the proposed aflibercept NPs demonstrated high encapsulation efficiency, a sustained drug release profile, and ideal physical characteristics for AMD treatment. This drug delivery system is an excellent candidate for further characterization using an ocular neovascularization in vivo model.

Keywords: PLGA; aflibercept; age-related macular degeneration; nanoparticles; vascular endothelial growth factor.

Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Figures

Figure 1
Figure 1
(A) Aflibercept nanoparticles were prepared via (B) the double emulsion diffusion method (* aqueous phase; ** organic phase).
Figure 2
Figure 2
AFL-NPs were characterized for (A) size distribution and (B) in vitro release profile compared to AFL solution.
Figure 3
Figure 3
SEM micrographs of AFL-NPs were obtained at (A) 18,000× and (B) 20,000× magnification. Both images were obtained using 5 kV acceleration voltage.
Figure 4
Figure 4
(A) AFL solution was non-toxic. AFL-NPs demonstrated similar cytotoxicity in ARPE-19 cells to blank NPs (n = 3, mean value ± SD); (B) after 72 h, VEGF-A expression by ARPE-19 cells was reduced post-treatment (0.5 µM) with AFL and AFL NPs (n = 3, mean ± SD).

Similar articles

See all similar articles

References

    1. CADTH . Aflibercept (Eylea): Treatment of Neovascular (Wet) Age-Related Macular Degeneration (Wamd) CADTH; Ottawa, ON, USA: 2015.
    1. Sato T., Takeuchi M., Karasawa Y., Enoki T., Ito M. Intraocular inflammatory cytokines in patients with neovascular age-related macular degeneration before and after initiation of intravitreal injection of anti-vegf inhibitor. Sci. Rep. 2018;8:1098. doi: 10.1038/s41598-018-19594-6. - DOI - PMC - PubMed
    1. Low A., Kansagara D., Freeman M., Fu R., Bhavsar K., Faridi A., Kondo K., Paynter R. Comparative Clinical and Economic Effectiveness of Anti-Vascular Endothelial Growth Factor Agents. Department of Veterans Affairs (US); Washington, DC, USA: 2017.
    1. Van Wijngaarden P., Coster D.J., Williams K.A. Inhibitors of ocular neovascularization: Promises and potential problems. JAMA. 2005;293:1509–1513. doi: 10.1001/jama.293.12.1509. - DOI - PubMed
    1. Subhani S., Vavilala D.T., Mukherji M. Hif inhibitors for ischemic retinopathies and cancers: Options beyond anti-vegf therapies. Angiogenesis. 2016:257–273. doi: 10.1007/s10456-016-9510-0. - DOI - PubMed
Feedback