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.
Highlights
A decrease in visual acuity can lead to alterations in the activities of daily living, quality of life, self-care, and mental health of an individual
Bysustained doing so, drug it was release were achieved by the nanoformulation of the protein demonstrated that a high encapsulation efficiency, uniform size distribution and sustained drug release were achieved by the nanoformulation of the protein AFL
The size and polydispersity index (PDI) of both the AFL and blank NPs were analyzed via dynamic light scattering (DLS) using a Wyatt DynaPro plate reader
Summary
A decrease in visual acuity can lead to alterations in the activities of daily living, quality of life, self-care, and mental health of an individual. Anti-VEGF agents possess a narrow therapeutic index, thereby necessitating frequent injections to maintain an acceptable concentration of drug in the eye [6] This frequency reduces patient compliance, and results in myriad potential adverse effects including retinal detachment, vitreous hemorrhage, and increased intraocular pressure [7,8]. Later, Swed et al encapsulated lysozyme and human transforming growth factor beta 1 (TGF-β1) separately in PLGA NPs to examine protein encapsulation They found that the NPs encapsulated at least 50% of each protein and possessed both a uniform size distribution (PDI less than 0.2) and sustained release properties over 30 days. Demonstrated that a high encapsulation efficiency, uniform size distribution and sustained drug release were achieved by the nanoformulation of the protein AFL
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