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Polymeric Propranolol Nanoparticles for Intraocular Delivery: Formulation, Characterization, and Vitreous Pharmacokinetics Publisher



Chaharband F1 ; Varshochian R2, 3 ; Dinarvand R3, 4 ; Sabbaghi H5 ; Rezaei Kanavi M6 ; Daftarian N6, 7 ; Nourinia R8
Authors
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Authors Affiliations
  1. 1. Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  3. 3. Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Ophthalmic Epidemiology Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  6. 6. Ocular Tissue Engineering Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  7. 7. Experimental Medicine, Department of Medicine, The University of British Columbia Faculty of Medicine, Vancouver, BC, Canada
  8. 8. Ophthalmic Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Source: Journal of Ophthalmic and Vision Research Published:2024


Abstract

Purpose: Recent studies have reported the promising effect of intravitreal propranolol on retinal neovascularization. However, rapid clearance and short half-life of the drug in the vitreous are the main drawbacks of this therapeutic approach. This study investigates the extension of the residence time of propranolol in the vitreous by polymeric nanoparticles (NPs) with the prospect of improving choroidal neovascularization treatment. Methods: The poly (lactic-co-glycolic) acid (PLGA) NPs were fabricated by a modified double emulsion solvent evaporation method and the obtained NPs were characterized for their size, poly dispersity index (PDI), and surface image. The in vitro release, cell cytotoxicity, and uptake of NPs were also evaluated. To investigate the effect of the vitreous pharmacokinetic drug loaded NPs versus that of the free propranolol, they were intravitreally injected into the rabbits’ eyes and the drug vitreous concentrations in defined intervals were analyzed by high performance liquid chromatography (HPLC). Results: The spherical NPs with about 230 nm size, and almost 10% drug loading were obtained. Based on the 3-(4, 5-Dimethylthiazol-2-Yl)-2, 5-Diphenyltetrazolium Bromide (MTT) outcomes, 30 µg/ml of propranolol was considered as the guide dosage in the intravitreal injection. Confocal microscopy images verified the presence of labeled NPs in the posterior segment after five days of receiving the injection. In vivo assay revealed that the vanishing rate of propranolol in rabbits treated with propranolol NPs was reduced at twice the rate as compared to that of the vanishing rate experienced with only the free drug. Conclusion: PLGA NPs can prolong the existence of propranolol in both vitreous and posterior ocular tissues, and thus, may provide an effective approach in treatment of posterior segment neovascularization. © 2024 Chaharband et al.
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