Table of Contents
Introduction
Glaucoma is a chronic and progressive optic neuropathy that is often associated with elevated intraocular pressure (IOP). Treatment primarily aims to lower IOP to reduce the risk of further optic nerve damage and vision loss. Conventional eye drops remain the mainstay of therapy; however, as studies have shown, less than 10% of an instilled drop can remain on the ocular surface after application due to tear turnover and blinking (Shazma et al., 2024). These limitations have spurred interest in developing novel drug delivery systems that improve bioavailability, extend drug residence time, and enhance patient adherence.
Dual drug therapy in glaucoma—such as combining a beta‐blocker like timolol with a carbonic anhydrase inhibitor like dorzolamide—has demonstrated superior IOP‐lowering efficacy compared to monotherapy. Despite the clinical benefits of fixed combination formulations, eye drops still suffer from issues of poor dosing accuracy and rapid washout. To address these challenges, a polymethacrylate‐based nanofiber insert has been developed using the electrospinning technique to fabricate a preservative‐free, implantable device that provides sustained release of both dorzolamide and timolol (Biomedicines, 2025).
Nanofiber Insert Fabrication and Characterization
The nanofiber insert is fabricated using electrospinning, a scalable process that produces continuous fibers with diameters in the nanometer range. Polymethacrylate, a biocompatible and bioadhesive polymer, is used as the matrix material because of its favorable physicochemical properties, including good film‐forming ability and compatibility with ocular tissues. During the fabrication process, solutions containing both dorzolamide and timolol are prepared and mixed with the polymer solution before subjecting the mixture to a high-voltage electric field. Under these conditions, uniform nanofibers with an average diameter of less than 465 nm are formed. Scanning electron microscopy confirms the uniform morphology and smooth surface of the fibers, essential for minimizing irritation when the insert is applied to the ocular surface (Biomedicines, 2025).
A Fourier-transform infrared spectroscopy (FTIR) analysis demonstrates that the drugs do not undergo significant chemical interaction with the polymer matrix, preserving the drug’s stability and efficacy. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) further validate the thermal stability and homogeneous composition of the nanofibers.
In Vitro Drug Release and Pharmacokinetic Evaluation
The in vitro release profiles of dorzolamide and timolol from the nanofiber insert have been studied extensively. The dual drug-loaded nanofiber insert demonstrates a controlled release pattern over an 80-hour period. In vitro studies indicate that both drugs are released in a sustained manner without a significant burst effect immediately after implantation. The area under the concentration–time curve (AUC₀₋₇₂) for dorzolamide and timolol are reported as 3216.63 ± 63.25 µg·h/mL and 2598.89 ± 46.65 µg·h/mL, respectively, with mean residence times (MRTs) of approximately 21.6 ± 0.19 hours for dorzolamide and 16.29 ± 6.44 hours for timolol (Biomedicines, 2025).
A summary of the in vitro release data is presented in Table 1.
| Drug | AUC₀₋₇₂ (µg·h/mL) | MRT (h) |
|---|---|---|
| Dorzolamide | 3216.63 ± 63.25 | 21.6 ± 0.19 |
| Timolol | 2598.89 ± 46.65 | 16.29 ± 6.44 |
Table 1. In vitro pharmacokinetic parameters of the dual drug-loaded nanofiber insert (Biomedicines, 2025).
In Vivo Studies and Ocular Compatibility
In vivo evaluation is critical to understanding the performance of ophthalmic drug delivery systems. The nanofiber insert was evaluated using a rabbit eye model. Following implantation, the inserts were well tolerated; clinical examinations showed no signs of ocular irritation or discomfort. The insert’s flexible and thin structure allows it to conform to the curvature of the ocular surface, minimizing the risk of mechanical irritation.
IOP measurements taken over a period of 72 hours post-implantation demonstrated a significant and sustained reduction in IOP. The controlled release of dorzolamide and timolol from the insert helped maintain therapeutic drug concentrations in the anterior chamber over an extended period, reducing the need for frequent dosing. Histopathological analysis of the ocular tissues revealed no evidence of inflammatory infiltrate or epithelial damage, confirming the high biocompatibility of the nanofiber system.
Cytotoxicity assays performed on cultured ocular cells further confirmed the safety of the formulation; over 90% of the cells remained viable when exposed to the dissolved components of the nanofiber insert (Biomedicines, 2025).
Advantages Over Traditional Eye Drops
The dual drug-loaded nanofiber insert offers several advantages compared to conventional eye drops:
- Enhanced Bioavailability: The controlled release of drugs over an extended period ensures a constant therapeutic concentration, increasing the bioavailability of the medications.
- Improved Patient Compliance: Reduced dosing frequency eases the burden on patients, particularly those who have difficulty administering traditional eye drops.
- Preservative-Free Formulation: By eliminating the need for preservatives, the nanofiber insert minimizes the risk of ocular surface toxicity—a significant concern in long-term glaucoma therapy.
- Enhanced Ocular Tolerability: The uniform and smooth nanofiber structure minimizes mechanical irritation and supports epithelial health.
- Potential for Combination Therapy: The system allows for the simultaneous delivery of multiple agents, which is particularly useful in treating complex disorders like glaucoma that often require multi-drug management.
Comparison with Other Novel Drug Delivery Approaches
Ophthalmic drug delivery research has led to various innovative systems including ocular inserts, contact lenses designed for drug delivery, and intraocular implants. Unlike contact lenses that require patient comfort and wearability considerations or intraocular implants that necessitate surgical procedures, nanofiber inserts represent a minimally invasive alternative that can be administered like traditional eye drops but with significantly prolonged drug release.
For example, several sustained-release drug delivery systems have been developed that employ hydrogels or ocular inserts loaded with anti-glaucoma agents. Although many of these methods have demonstrated favorable pharmacokinetic profiles, the nanofiber insert’s nanoscale architecture offers superior control over drug loading and release compared to conventional systems (Biomedicines, 2025). In addition, the absence of preservatives—often implicated in ocular surface disease in glaucoma patients—provides a critical advantage in the long-term management of glaucoma.
Future Perspectives
The promising performance of dual drug-loaded nanofiber inserts opens avenues for further research and development. Future research may focus on:
- Optimization of Drug Release Profiles: Fine-tuning the polymer composition and fiber morphology to further optimize drug release patterns.
- Long-Term Efficacy and Safety Studies: Extended in vivo evaluations to assess the long-term impact on both IOP control and ocular tissue health.
- Scale-Up and Manufacturing: Improving fabrication scalability to produce nanofiber inserts on a commercial scale.
- Personalized Treatment: Customizing drug ratios and release kinetics tailored to individual patient needs.
- Integration with Advanced Materials: Incorporating novel materials such as graphene derivatives could potentially augment the mechanical properties and drug loading capacity of these inserts.
Advancements in nanotechnology and materials science will likely contribute to the emergence of even more sophisticated ophthalmic drug delivery systems, ultimately leading to better clinical outcomes for patients with glaucoma.
Frequently Asked Questions (FAQ)
What are the main disadvantages of traditional eye drops in glaucoma treatment?
Traditional eye drops suffer from rapid drug washout, low bioavailability, and the need for frequent administration due to tear turnover and blinking. Additionally, preservatives in these drops can cause ocular surface toxicity.
How does the dual drug-loaded nanofiber insert improve drug delivery in glaucoma?
The nanofiber insert provides a controlled and sustained release of dorzolamide and timolol over approximately 80 hours. This extended release ensures a steady therapeutic drug concentration, reducing the frequency of dosing and improving patient compliance.
What role does the polymer (polymethacrylate) play in the nanofiber insert?
Polymethacrylate acts as a biocompatible matrix that is capable of forming uniform nanofibers. Its properties allow for effective drug entrapment, controlled release, adhesion to the ocular surface, and minimal irritation upon application.
Are there any adverse effects associated with the nanofiber insert?
In vitro cytotoxicity assays and in vivo evaluations in rabbit models have shown that the nanofiber insert is well tolerated, with no significant ocular irritation or inflammatory response observed, thanks in part to its smooth morphology and preservative-free formulation.
How does the performance of nanofiber inserts compare with other novel ophthalmic drug delivery systems?
Unlike ocular inserts or contact lenses that may have limitations regarding patient comfort or invasiveness, the nanofiber insert allows for easy administration and sustained drug delivery without significant side effects. Furthermore, it benefits from a higher bioavailability and the absence of preservatives, which can compromise the ocular surface.
Conclusion
The development of a dual drug-loaded polymethacrylate-based nanofiber insert represents a significant advancement in ophthalmic drug delivery for glaucoma therapy. By combining the IOP-lowering actions of dorzolamide and timolol in a single, preservative-free insert, this technology addresses many of the limitations associated with traditional eye drops. The controlled release mechanism offers prolonged therapeutic effects and has been shown to be safe and effective in preclinical studies. With continued research and optimization, such inserts have the potential to improve patient outcomes significantly and pave the way for personalized and long-lasting glaucoma management.
References
- Shazma, G., Iqbal, Z., & Nasir, F. (2024). Self-assembled latanoprost loaded soluplus nanomicelles as an ophthalmic drug delivery system for the management of glaucoma. Retrieved from https://doi.org/10.1038/s41598-024-78244-2
- Sridharan, K. (2024). Systemic adverse drug events to topical prostaglandin analogs for treating glaucoma: A retrospective focused pharmacovigilance study. Retrieved from https://doi.org/10.1186/s12886-024-03823-w
- Development of a conjunctival contact–type drug delivery device for latanoprost using hyaluronic acid. (n.d.). Retrieved from https://pubmed.ncbi.nlm.nih.gov/11795754/
- Ocular Tissue Distribution of Omidenepag Isopropyl in Rabbits and Cynomolgus Monkeys. (n.d.). Retrieved from https://pubmed.ncbi.nlm.nih.gov/11552074/
- Graphene derivative based hydrogels in biomedical applications. (n.d.). Retrieved from https://pubmed.ncbi.nlm.nih.gov/11490963/
- Antimicrobial Preservatives in Cyclodextrin-Containing Drug Formulations. (2024). Retrieved from https://doi.org/10.3390/pharmaceutics16121601
- Managing Ocular Surface Disease in Glaucoma Treatment: A Systematic Review. (2024). Retrieved from https://doi.org/10.3390/bioengineering11101010
- Management and toxicological analysis of ocular hypertension after EyeCee® ONE intraocular lens implantation: A case series. (2024). Retrieved from https://doi.org/10.1186/s12886-024-03810-1
- Development and Evaluation of Polymethacrylate-Based Ophthalmic Nanofiber Inserts Containing Dual Drug-Loaded Dorzolamide and Timolol: In Vivo Study in Rabbit’s Eye. (2025). Retrieved from https://doi.org/10.3390/biomedicines13010200
This article has been prepared to provide an in-depth analysis of the current research and developments in ophthalmic nanofiber-based drug delivery systems for glaucoma, based on recent scientific publications.
