(W0930-07-42) Development of a Drug-Eluting, 3D-Printed, Injectable Intraocular Lens for Glaucoma Treatment

Purpose: Current glaucoma treatments face challenges such as rapid tear clearance and low drug bioavailability with eye drops. This study introduces a 3D-printed intraocular lens (IOL) integrated with timolol-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres to enable sustained drug delivery, addressing compliance issues and enhancing therapeutic efficacy. In this study, we consider one of the most common drugs used in IOP management in glaucoma patients, timolol We develop a poly(acrylamide–sodium acrylate) hydrogel (PAH) IOL loaded with drug-containing biodegradable Poly-lactic-co-glycolic acid (PLGA) microspheres, which can release timolol in a sustained manner to treat glaucoma.

Methods: PLGA microspheres encapsulating timolol maleate were synthesized via a water-in-oil-in-water (w/o/w) double emulsion method. Microspheres were incorporated into a poly(acrylamide–sodium acrylate) hydrogel (PAH) matrix, cast using a 3D-printed mold. Drug release kinetics over 7 weeks, hydrogel transparency, and mechanical properties were evaluated.

Results: The encapsulation of timolol-loaded microspheres in the PAH film, PAH loaded microspheres (PAH-(504A)MS), showed more sustained release than compared to the microspheres, (504A)MS. PAH-(504A)MS showed sustained release for ~50 days, which is ~3 times higher than that obtained for (504A)MS. The rheological studies of PAH film and PAH-(504A)MS showed that microsphere loaded PAH film has higher compressibility than PAH film, which denotes its ease of injectability.

Conclusion: This 3D-printed drug-eluting IOL offers a patient-friendly alternative to daily eye drops, combining sustained timolol delivery with biocompatibility. Our drug-loaded IOL is capable of sustaining drug release at least for 7 weeks. With a flexible IOL, it is possible to perform a cataract surgery using a smaller incision, which can be beneficial to patients in the long run. The resulting device demonstrated good flexibility and thus may be easily injected. Further, it exhibits excellent optical transparency, fine visco-elastic properties, and a great swelling capacity of up to 135% in PBS solution. The integration of PLGA microspheres within a hydrogel matrix extends release duration while maintaining optical clarity, positioning it as a promising long-term solution for glaucoma management.

References: 1. X. Zhang, X. Cao, and P. Qi, “Therapeutic contact lenses for ophthalmic drug delivery: major challenges,” J Biomater Sci Polym Ed, vol. 31, no. 4, pp. 549–560, Mar. 2020, doi: 10.1080/09205063.2020.1712175.
2. Desai et al., “Multiple drug delivery from the drug-implants-laden silicone contact lens: Addressing the issue of burst drug release,” Materials Science and Engineering: C, vol. 112, p. 110885, Jul. 2020, doi: 10.1016/J.MSEC.2020.110885.
3. N. Yu, F. Fang, B. Wu, L. Zeng, and Y. Cheng, “State of the art of intraocular lens manufacturing,” International Journal of Advanced Manufacturing Technology, vol. 98, no. 5–8, pp. 1103–1130, Sep. 2018, doi: 10.1007/S00170-018-2274-5.
4. J. P. Bertram, S. S. Saluja, J. McKain, and E. B. Lavik, “Sustained delivery of timolol maleate from poly(lactic-co-glycolic acid)/poly(lactic acid) microspheres for over 3 months,” J Microencapsul, vol. 26, no. 1, pp. 18–26, 2009, doi: 10.1080/02652040802095250.
5. H. Cui, P. Li, Z. Su, S. Guan, H. Dong, and X. Dong, “Preparation and Stability Study of an Injectable Hydrogel for Artificial Intraocular Lenses,” Polymers (Basel), vol. 16, no. 18, p. 2562, Sep. 2024, doi: 10.3390/POLYM16182562.
6. J. W. Li et al., “Biosafety of a 3D-printed intraocular lens made of a poly(acrylamide-co-sodium acrylate) hydrogel in vitro and in vivo,” Int J Ophthalmol, vol. 13, no. 10, pp. 1521–1530, Oct. 2020, doi: 10.18240/ijo.2020.10.03.

Acknowledgements: The authors thank the financial support of Anusandhan National Research Foundation, India, project number CRG/2022/003774. The authors also gratefully acknowledge the facilities provided by the Indian Institute of Technology Roorkee.