Nano-in-Nano Dendrimer Gel Particles for Efficient Topical Delivery of Antiglaucoma Drugs into the Eye
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.
J. Wang and B. Li and D. Huang and P. Norat and M. Grannonico and R. C. Cooper and Q. Gui and W. Nam Chow and X. Liu and H. Yang, "Nano-in-Nano Dendrimer Gel Particles for Efficient Topical Delivery of Antiglaucoma Drugs into the Eye," Chemical Engineering Journal, vol. 425, article no. 130498, Elsevier, Dec 2021.
The definitive version is available at https://doi.org/10.1016/j.cej.2021.130498
Chemical and Biochemical Engineering
Keywords and Phrases
Brimonidine; Dendrimer; Glaucoma; Microgel; Nanogel
International Standard Serial Number (ISSN)
Article - Journal
© 2021 Elsevier, All rights reserved.
01 Dec 2021