Micro/Nanoparticle Delivery Systems for Ocular Diseases.

Micro- (MPs) and nanoparticles (NPs) have been recently studied for their application in ophthalmic drug delivery. These drug delivery systems are able to circumvent the ocular barriers that currently limit the efficacy of conventional treatments, as well as provide a more sustained release of drug, reducing the frequency of administration and increasing patient compliance. This review summarizes the recent trends in ophthalmic research from conventional treatment to the utilization of MPs and NPs as drug carriers.

Nanoparticle drug delivery characterization for fluticasone propionate and in vitro testing 1.

Glucocorticoids, such as fluticasone propionate (FP), are used for the treatment of inflammation and alleviation of nasal symptoms and allergies, and as an antipruritic. However, both short- and long-term therapeutic use of glucocorticoids can lead to muscle weakness and atrophy. In the present study, we evaluated the feasibility of the nanodelivery of FP with poly(dl-lactide-co-glycolide) (PLGA) and tested in vitro function. FP-loaded PLGA nanoparticles were prepared via nanoprecipitation and morphological characteristics were studied via scanning electron microscopy. FP-loaded nanoparticles demonstrated an encapsulation efficiency of 68.6% ± 0.5% with a drug loading capacity of 4.6% ± 0.04%, were 128.8 ± 0.6 nm in diameter with a polydispersity index of 0.07 ± 0.008, and displayed a zeta potential of -19.4 ± 0.7. A sustained in vitro drug release pattern was observed for up to 7 days. The use of fluticasone nanoparticle decreased lipopolysaccharide (LPS)-induced lactate dehydrogenase release compared with LPS alone in C2C12 treated cells. FP also decreased expression of LPS-induced inflammatory genes in C2C12 treated cells as compared with LPS alone. Taken together, the present study demonstrates in vitro feasibility of PLGA-FP nanoparticle delivery to the skeletal muscle cells, which may be beneficial for treating inflammation.

Nanodelivery of doxorubicin for age-related macular degeneration.

OBJECTIVE: Polymeric nanoparticles (NPs) containing doxorubicin (DOX) were prepared for the inhibition of hypoxia-induced factor 1α (HIF-1α). SIGNIFICANCE: HIF-1α is responsible for the upregulation of several angiogenic factors, including vascular endothelial growth factor (VEGF). DOX inhibits HIF-1α but is highly toxic. By encapsulating DOX in NPs, drug delivery will be sustained and toxicity will be reduced without limiting efficacy. METHODS: DOX NPs were prepared using both polylactic coglycolic acid (PLGA) and chitosan. PLGA NPs were prepared via nanoprecipitation (NPC) and single and double emulsion diffusion (SE; DE). Chitosan NPs were formulated using ionic gelation (IG), and complex coacervation (CC). Size, polydispersity index (PDI), and zeta potential (ZP) were determined via dynamic light scattering (DLS) (n = 3). The encapsulation efficiency (EE), drug loading capacity (DLC) (n = 3) and in vitro drug release profiles (IVR) at 37 °C (n = 4) were analyzed via spectroscopy at 480 nm (λmax). The cytotoxicity of each formulation as well as free DOX solution in ARPE-19 cells was determined via MTT assay after 24 h (n = 3). HIF-1α and VEGF inhibition in ARPE-19 cells were measured via ELISA (n = 3). RESULTS: The results were consistent with the hypothesis; the NP formulations decreased HIF-1α and VEGF-A expression in ARPE-19 cells with reduced cytotoxicity. SE, DE, and CC demonstrated low ZP as well as the most rapid drug release of the tested formulations. FTIR confirmed the presence of DOX on the SE NP surface, indicating instability. CONCLUSIONS: SE, DE, and CC destabilized. NPC was the most efficient formulation for the nanodelivery of DOX for AMD.

Utilization of Apatinib-Loaded Nanoparticles for the Treatment of Ocular Neovascularization.

BACKGROUND: The current treatment of ocular neovascularization requires frequent intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents that cause severe side effects. OBJECTIVE: The purpose of this study is to prepare and characterize a novel nanoscale delivery system of apatinib for ocular neovascularization. METHODS: The optimized formulation showed a particle size of 135.04 nm, polydispersity index (PDI) of 0.28 ± 0.07, encapsulation efficiency (EE) of 65.92%, zeta potential (ZP) of -23.70 ± 8.69 mV, and pH of 6.49 ± 0.20. In vitro release was carried out to demonstrate a 3.13-fold increase in the sustainability of apatinib-loaded nanoparticles versus free apatinib solution. RESULT: Cell viability and VEGFA and VEGFR2 expression were analyzed in animal retinal pigment epithelial (ARPE-19) cells. CONCLUSION: The results confirmed the hypothesis that apatinib nanoparticles decreased toxicity (1.36 ± 0.74 fold) and efficient VEGF inhibition (3.51 ± 0.02 fold) via VEGFR2 mediation.

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

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.

Nanodrug delivery platform for glucocorticoid use in skeletal muscle injury.

Glucocorticoids are utilized for their anti-inflammatory properties in the skeletal muscle and arthritis. However, the major drawback of use of glucocorticoids is that it leads to senescence and toxicity. Therefore, based on the idea that decreasing particle size allows for increased surface area and bioavailability of the drug, in the present study, we hypothesized that nanodelivery of dexamethasone will offer increased efficacy and decreased toxicity. The dexamethasone-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles were prepared using nanoprecipitation method. The morphological characteristics of the nanoparticles were studied under scanning electron microscope. The particle size of nanoparticles was 217.5 ± 19.99 nm with polydispersity index of 0.14 ± 0.07. The nanoparticles encapsulation efficiency was 34.57% ± 1.99% with in vitro drug release profile exhibiting a sustained release pattern over 10 days. We identified improved skeletal muscle myoblast performance with improved closure of the wound along with increased cell viability at 10 nmol/L nano-dexamethasone-PLGA. However, dexamethasone solution (1 µmol/L) was injurious to cells because the migration efficiency was decreased. In addition, the use of dexamethasone nanoparticles decreased lipopolysaccharide-induced lactate dehydrogenase release compared with dexamethasone solution. Taken together, the present study clearly demonstrates that delivery of PLGA-dexamethasone nanoparticles to the skeletal muscle cells is beneficial for treating inflammation and skeletal muscle function.