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Research Title:��The Renin-Angiotensin System and its Role in Neuroprotective Strategies in a Glaucoma Model

���ܱ����������ǰ���:��Nicole Carnt, Andrew White, Ushasree Pattamatta

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Abstract

Glaucoma is characterized by progressive degeneration of retinal ganglion cells (RGCs), underscoring the need for neuroprotective interventions that achieve sustained intraocular exposure following topical administration. Here, irbesartan-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles were engineered by nanoprecipitation and evaluated across physicochemical, in vitro, ex vivo, and in vivo domains. The optimized formulation exhibited a hydrodynamic diameter of 197.3 nm (polydispersity index 0.188), a moderately negative ζ-potential (−22.2 ± 0.2 mV), high encapsulation efficiency (80.11 ± 3.02 %), and favourable drug loading (10.10 ± 0.42 %). In vitro release showed an initial diffusion-driven burst (42 % at 2 h), attributed to desorption and diffusion of surface-associated drug, followed by sustained release to 74 % at 24 h governed by matrix diffusion and polymer erosion. Cytocompatibility was confirmed in L929 fibroblasts across 5–200 µg mL⁻¹ (nanoparticles: 89.1–98.9 % viability; free irbesartan: 84.5–100.7 %).

Neuroprotective activity was first established ex vivo in retinal explants, where Irb-PLGA increased RGC survival by 54 % at 1 µM (p = 0.0216) and 64 % at 10 µM (p = 0.0013) versus DMEM; free irbesartan produced a 92 % increase (p = 0.0017). At a tenfold lower nominal concentration (1 µM vs 10 µM free irbesartan), Irb-PLGA retained 80% of the free-drug effect ex vivo, indicating a dose-sparing advantage. In vivo (mouse optic nerve crush), Irb-PLGA improved RGC survival by 151 % at 1 µM and 201 % at 10 µM versus blank PLGA (both p < 0.001), corresponding to 61 % and 73 % of the contralateral baseline, respectively.

Collectively, these findings indicate that PLGA encapsulation overcomes the aqueous insolubility of irbesartan, exhibits an initial burst yet sustained release, and confers statistically significant neuroprotection in complementary ex vivo and in vivo paradigms.

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Biography

Adrian Julian Marcus is a final year PhD candidate specializing in ocular drug delivery and neuroprotection. His research develops PLGA nanoparticles loaded with irbesartan to improve retinal delivery and protect retinal ganglion cells in glaucoma models. He integrates in vivo mouse and rat work, ex vivo retinal explants, and in vitro fibroblast culture, combining MTT viability tests, immunofluorescence, Western blotting, confocal imaging, and TEM. Adrian builds reproducible image analysis pipelines in ImageJ and Python (OpenCV) to quantify RGC survival and morphology, and he uses dialysis methods to characterize drug release. His research interest is to discover novel therapeutic strategies, especially in ocular neuroscience.

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Education:��M.Sc., Biomedical Science (Pharmacology), B.Sc. (Hons), Biotechnology

Awards:��Australian Government Research Training Program (RTP) Scholarship – ���������¼�, 2022–2025

Conference Attendance:��Screening for Intraocular Pressure-Lowering Effect of Pyrimidazobenzimidazole Derivatives in Ocular Normotensive Rats. 13th Asia Pacific Federation of Pharmacologists (APFP) Meeting, Thailand (Feb 2016)