Triamcinolone acetonide nanoparticles incorporated in thermoreversible gels for age-related macular degeneration

Abstract

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the US affecting millions yearly. It is characterized by intraocular neovascularization, inflammation and retinal damage which can be ameliorated through intraocular injections of glucocorticoids. However, the complications that arise from repetitive injections as well as the difficulty posed by targeting the posterior segment of the eye make this interesting territory for the development of novel drug delivery systems (DDS). In the present study, we described the development of a DDS composed of triamcinolone acetonide-encapsulated PEGylated PLGA nanoparticles (NP) incorporated into PLGA-PEG-PLGA thermoreversible gel and its use against VEGF expression characteristic of AMD. We found that the NP with mean size of 208 ± 1.0 nm showed uniform size distribution and exhibited sustained release of the drug. We also demonstrated that the polymer can be injected as a solution and transition to a gel phase based on the biological temperature of the eye. Additionally, the proposed DDS was non-cytotoxic to ARPE-19 cells and significantly reduced VEGF expression by 43.5 ± 3.9% as compared to a 1.53 ± 11.1% reduction with triamcinolone. These results suggest the proposed DDS will contribute to the development of novel therapeutic strategies for AMD.

Corneal permeation properties of a charged lipid nanoparticle carrier containing dexamethasone

“…21,22 Recently, drug carriers have been developed that combine two or more molecules, although effective delivery to the posterior segment by anterior corneal administration remains problematic. [23][24][25][26][27] Lipid nanoparticles (L/NPs) can be used to encapsulate and deliver poorly soluble drugs and can enable greater drug permeation into tissues via lipid membrane fusion. We hypothesized that combining L/NPs with the water-soluble cationic polysaccharide chitosanwhich is biodegradable, adhesive, and biocompatible and has superior penetration -can improve L/NP drug loading and release (Figure 2).…”

Micro/Nanoparticle Delivery Systems for Ocular Diseases

“…NPs are able to be manipulated by altering the weight and hydrophilicity, resulting in a more sustained release. 9 Formulation and Characterization Methods The two primary MP/NP formulation methods are ''top-down'' and ''bottom-up.'' The ''bottom-up'' approach involves manipulating thermodynamic properties to build nanostructures from smaller molecules and atoms.…”

“…Therefore, ocular neovascularization can be combated with a variety of antiangiogenic therapies targeting these different factors. 9,20 Vascular endothelial growth factor (VEGF) plays a central role in mediating angiogenesis and vascular permeability. The presence of elevated levels of VEGF has been observed in neovascular membranes in some diseases (age-related macular degeneration [AMD] and diabetic retinopathy [DR]), and its intraocular levels show strong correlation with the neovascularization associated with these pathologies.…”

“…Neovascularization facilitates the repair of damaged tissues by promoting the formation of new vessels from preexisting vessels. 9 These newly formed vessels replace any vessels damaged during injury. 48 However, neovascularization in the choroid exacerbates the underlying complication.…”

Optimization of novel pentablock copolymer based composite formulation for sustained delivery of peptide/protein in the treatment of ocular diseases

“…Many polymeric systems such as poly lactide-co-glycolide (PLGA) (Bilati et al, 2005), PCL-PEG-PCL (Jia et al, 2008), PEG-PCL (Pourcelle et al, 2007), PEG-PLA (Lee et al, 2007), PEG-PLGA (Hirani et al, 2014), PLGA-PEG-PLGA and poloxamers (Radivojsa et al, 2013) have been evaluated for the design of controlled delivery of protein, peptide as well as small molecules. Protein molecules are very fragile and sensitive towards external stimuli.…”