Title

Nano-in-Nano Dendrimer Gel Particles for Efficient Topical Delivery of Antiglaucoma Drugs into the Eye

Abstract

Low bioavailability of topically applied drugs remains a significant challenge for long-term glaucoma therapy. To enhance drug delivery efficiency, we developed dendrimer gel particles that collectively exhibit structural benefits of dendrimer, hydrogel, and particles, using the inverse emulsion method coupled with the highly efficient aza-Michael addition reaction (IEaMA). This hierarchical approach would maximize the utility of the structural features of existing ocular drug delivery systems. We have tested the delivery efficiency and efficacy of two first-line antiglaucoma drugs, brimonidine tartrate (BT) and timolol maleate (TM), which were loaded into dendrimer gel particles of various sizes, i.e., nDHP (nano-in-nano dendrimer hydrogel particles, ~200 nm), μDHP3 (3 μm), and μDHP10 (9 μm). We found that nDHP was superior to μDHP3 and μDHP10 in terms of cytocompatibility, degradability, drug release kinetics, and corneal permeability. The nDHPs increased drug corneal permeability by 17-fold compared to plain drug solution and enabled zero-order prolonged drug release kinetics. The nDHP-based formulation demonstrated pronounced IOP-lowering effects in both single-dose test and 7-day chronic daily dosing test in both Brown Norway rats and glaucoma mice. Taken together, we have developed nano-in-nano dendrimer gel particles for precise dosing and enabling sustained and synergistic efficacy of antiglaucoma drugs, which could be clinically impactful for improving glaucoma treatment.

Department(s)

Chemical and Biochemical Engineering

Comments

This work was supported, in part, by the National Institutes of Health (R01EY024072 and R01EY029121) and the Fundamental Research Funds for the Central Universities (Grant No. 20822041D4094, 1082204112665).

Keywords and Phrases

Brimonidine; Dendrimer; Glaucoma; Microgel; Nanogel

International Standard Serial Number (ISSN)

1385-8947

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2021 Elsevier, All rights reserved.

Publication Date

01 Dec 2021

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