Abstract

Efficient topical drug delivery remains a significant challenge in glaucoma management. Although nanoparticle formulations offer considerable promise, their complex preparation processes, co-delivery issues, and batch consistency have hindered their potential. A scalable fabrication strategy is developed here for preparing solid drug nanoparticles (SDNs) with enhanced drug delivery efficiency. Utilizing hydrophobic antiglaucoma drugs brimonidine (BM) and betaxolol (BX), uniform fixed combination BM/BX SDNs are fabricated through a continuous process, improving batch-to-batch consistency for combined glaucoma treatment. With trehalose being used as a lyoprotectant, BM/BX SDNs can be stored as dry powder and easily reconstituted in phosphate buffered saline. Importantly, reconstituted BM/BX SDNs form clear, homogenous solutions, and exhibit negligible cytotoxicity and irritation, making them well-suited for topical administration as eyedrops. Ex vivo and in vivo studies demonstrated that topically applied BM/BX SDNs permeate through the cornea significantly (about two-fold to three-fold) compared to their hydrophilic counterparts, i.e., brimonidine tartrate, and betaxolol hydrogen chloride. Notably, BM/BX SDNs displayed consistent intraocular pressure lowering effects in vivo in both normotensive rats and glaucoma mice. Collectively, this study demonstrates the potential of the scalable fabrication strategy and the resultant BM/BX SDNs for improving glaucoma management through eyedrops.

Department(s)

Chemical and Biochemical Engineering

Publication Status

Open Access

Comments

Glaucoma Research Foundation, Grant R01EY035088

Keywords and Phrases

anti-glaucoma drugs; cornea permeation; ocular hypertension; scalable fabrication; solid drug nanoparticles

International Standard Serial Number (ISSN)

2198-3844

Document Type

Article - Journal

Document Version

Final Version

File Type

text

Language(s)

English

Rights

© 2024 The Authors, All rights reserved.

Creative Commons Licensing

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Publication Date

21 Aug 2024

PubMed ID

38874068

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