Co-delivery of brinzolamide and timolol from micelles-laden contact lenses: in vitro and in vivo evaluation
Abstract
Purpose Traditional eye drops exhibit a modest bioavailability ranging from 1 to 5%, necessitating recurrent application. Thus, a contact lens-based drug delivery system presents substantial benefits. Nonetheless, pharmaceutical agents exhibiting poor solubility may compromise the quintessential characteristics of contact lenses and are, consequently, deemed unsuitable for incorporation. To address this issue, the present study has engineered a novel composite drug delivery system that amalgamates micellar technology with contact lenses, designed specifically for the efficacious conveyance of timolol and brinzolamide.Methods Utilizing mPEG-PCL as the micellar material, this study crafted mPEG-PCL micelles loaded with brinzolamide and timolol through the film hydration technique. The micelle-loaded contact lens was fabricated employing the casting method; a uniform mixture of HEMA and EGDMA with the mPEG-PCL micelles enshrouding brinzolamide and timolol was synthesized. Following the addition of a photoinitiator, 50 μL of the concoction was deposited into a contact lens mold. Subsequently, the assembly was subjected to polymerization under 365 nm ultraviolet light for 35 min, resulting in the formation of the micelle-loaded contact lenses.Results In the present article, we delineate the construction of a micelle-loaded contact lens designed for the administration of brinzolamide and timolol in the treatment of glaucoma. The study characterizes crucial properties of the micelle-loaded contact lenses, such as transmittance and ionic permeability. It was observed that these vital attributes meet the standard requirements for contact lenses. In vitro release studies revealed that timolol and brinzolamide could be gradually liberated over periods of up to 72 and 84 h, respectively. In vivo pharmacodynamic evaluation showed a significant reduction in intraocular pressure and a relative bioavailability of 10.84 times that of commercially available eye drops. In vivo pharmacokinetic evaluation, MRT was significantly increased, and the bioavailability of timolol and brinzolamide was 2.71 and 1.41 times that of eye drops, respectively. Safety assessments, including in vivo irritation, histopathological sections, and protein adsorption studies, were conducted as per established protocols, confirming that the experiments were in compliance with safety standards.In conclusion The manuscript delineates the development of a safe and efficacious micelle-loaded contact lens drug delivery system, which presents a novel therapeutic alternative for the management of glaucoma.
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mPEG-PCL micelles CLs containing brinzolamide and timolol showed gradual liberation over durations reaching up to 72 h for timolol and 84 h for brinzolamide in vitro.
“In vitro release studies revealed gradual liberation over durations reaching up to 72 h for timolol and 84 h for brinzolamide respectively.”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [163]
In vivo pharmacodynamic evaluations demonstrated markedly increased bioavailability and substantial reductions in IOP in the rabbit model for mPEG-PCL micelles CLs.
“In vivo pharmacodynamic evaluations demonstrated markedly increased bioavailability and substantial reductions in IOP in the rabbit model [163].”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [163]
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- Authors
- Yang, H., Zhang, F., Fan, Y., Zhang, J., Fang, T., Xing, D., Zhen, Y., Nie, Z., Liu, Y., Wang, D., & Li, J.
- Affiliations
- Shenyang Pharmaceutical University (CN)
- Corresponding author
- Wang, Dongkai
- Li, Ji
- Venue
- Pharmaceutical Research
- Published
- 2024-02-16
- Volume
- 41
- Issue
- 3
- Pages
- 531-546
- ISSN
- 0724-8741 (ISSN-L)
- 1573-904X
- OpenAlex
- W4392718536
- Cited by
- 14
- References
- 46
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 3
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Pharmaceutical Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Liaoning Provincial Department of Human Resources and Social Security (2020LJC16)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ocular Surface and Contact Lens
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Keywords
- brinzolamide, timolol, glaucoma, intraocular pressure reduction, ocular drug delivery, sustained drug release, bioavailability, pharmacokinetics, photopolymerization, eye irritation, protein adsorption, film hydration, poorly water-soluble drugs, contact lens safety
- MeSH terms
- Antihypertensive Agents, Contact Lenses, Glaucoma, Humans, Micelles, Ophthalmic Solutions, Polyesters, Polyethylene Glycols, Sulfonamides, Thiazines, Timolol, Drug Delivery Systems
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