title: 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.
authors.affiliation: a Department of Pharmaceutical Sciences , USF College of Pharmacy, University of South Florida , Tampa , FL , USA and.|b School of Biomedical Engineering and Sciences, Virginia Tech-Wake Forest University , Blacksburg , VA , USA.
authors.forename: Anjali
authors.initials: A
authors.lastname: Hirani
authors.affiliation: a Department of Pharmaceutical Sciences , USF College of Pharmacy, University of South Florida , Tampa , FL , USA and.
authors.forename: Aditya
authors.initials: A
authors.lastname: Grover
authors.affiliation: b School of Biomedical Engineering and Sciences, Virginia Tech-Wake Forest University , Blacksburg , VA , USA.
authors.forename: Yong W
authors.initials: YW
authors.lastname: Lee
authors.affiliation: a Department of Pharmaceutical Sciences , USF College of Pharmacy, University of South Florida , Tampa , FL , USA and.
authors.forename: Yashwant
authors.initials: Y
authors.lastname: Pathak
authors.affiliation: a Department of Pharmaceutical Sciences , USF College of Pharmacy, University of South Florida , Tampa , FL , USA and.
authors.forename: Vijaykumar
authors.initials: V
authors.lastname: Sutariya
mesh_terms: D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods; D005782:Gels; D006801:Humans; D008268:Macular Degeneration / Q000188:drug therapy / Q000378:metabolism*; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D011098:Polyglactin 910 / Q000008:administration & dosage / Q000737:chemistry; D055213:Retinal Pigment Epithelium / Q000187:drug effects* / Q000378:metabolism*; D013696:Temperature; D014222:Triamcinolone Acetonide / Q000008:administration & dosage* / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000096:biosynthesis
chemical_list: D005782:Gels; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C528571:poly(lactic-co-glycolic acid)-polyethylene glycol-poly(lactic-co-glycolic acid); D011098:Polyglactin 910; D011092:Polyethylene Glycols; D014222:Triamcinolone Acetonide
keywords: Age-related macular degeneration; PLGA nanoparticles; VEGF; thermoreversible gel; triamcinolone acetonide