Comprehensive Ocular and Systemic Safety Evaluation of Polysialic Acid-Decorated Immune Modulating Therapeutic Nanoparticles (PolySia-NPs) to Support Entry into First-in-Human Clinical Trials.
Document Type
Article
Publication Date
4-9-2024
Publication Title
Pharmaceuticals
Abstract
An inflammation-resolving polysialic acid-decorated PLGA nanoparticle (PolySia-NP) has been developed to treat geographic atrophy/age-related macular degeneration and other conditions caused by macrophage and complement over-activation. While PolySia-NPs have demonstrated pre-clinical efficacy, this study evaluated its systemic and intraocular safety. PolySia-NPs were evaluated in vitro for mutagenic activity using Salmonella strains and E. coli, with and without metabolic activation; cytotoxicity was evaluated based on its interference with normal mitosis. PolySia-NPs were administered intravenously in CD-1 mice and Sprague Dawley rats and assessed for survival and toxicity. Intravitreal (IVT) administration in Dutch Belted rabbits and non-human primates was assessed for ocular or systemic toxicity. In vitro results indicate that PolySia-NPs did not induce mutagenicity or cytotoxicity. Intravenous administration did not show clastogenic activity, effects on survival, or toxicity. A single intravitreal (IVT) injection and two elevated repeat IVT doses of PolySia-NPs separated by 7 days in rabbits showed no signs of systemic or ocular toxicity. A single IVT inoculation of PolySia-NPs in non-human primates demonstrated no adverse clinical or ophthalmological effects. The demonstration of systemic and ocular safety of PolySia-NPs supports its advancement into human clinical trials as a promising therapeutic approach for systemic and retinal degenerative diseases caused by chronic immune activation.
Volume
17
Issue
4
First Page
481
Recommended Citation
Krishnan A, Callanan DG, Sendra VG, Lad A, Christian S, Earla R, et al. [Hassan TS]. Comprehensive ocular and systemic safety evaluation of polysialic acid-decorated immune modulating therapeutic nanoparticles (PolySia-NPs) to support entry into first-in-human clinical trials. Pharmaceuticals. 2024 Apr 9;17(4):481. doi: 10.3390/ph17040481. PMID: 38675441.
DOI
10.3390/ph17040481
ISSN
1424-8247
PubMed ID
38675441
