Jump to:
Peer-reviewed articles
2023
Pereira-da-Mota,A. F., Vivero-Lopez, M., Garg,P., Phan,C-M., Concheiro,A., Jones,L., Alvarez-Lorenzo,C.
In vitro–in vivo correlation of drug release profiles from medicated contact lenses using an in vitro eye blink model
Drug Delivery and Translational Research 2023;13(4):1116-1127
[ Show Abstract ]
There is still a paucity of information on how in vitro release profiles from drug-loaded contact lenses (CLs) recorded in 3D printed eye models correlate with in vivo profiles. This work aims to evaluate the release profiles of two drug-loaded CLs in a 3D in vitro eye blink model and compare the obtained results with the release in a vial and the drug levels in tear fluid previously obtained from an animal in vivo study. In vitro release in the eye model was tested at two different flow rates (5 and 10 µL/min) and a blink speed of 1 blink/10 s. Model CLs were loaded with two different drugs, hydrophilic pravastatin and hydrophobic resveratrol. The release of both drugs was more sustained and lower in the 3D eye model compared to the in vitro release in vials. Interestingly, both drugs presented similar release patterns in the eye model and in vivo, although the total amount of drugs released in the eye model was significantly lower, especially for resveratrol. Strong correlations between percentages of pravastatin released in the eye model and in vivo were found. These findings suggest that the current 3D printed eye blink model could be a useful tool to measure the release of ophthalmic drugs from medicated CLs. Nevertheless, physiological parameters such as the composition of the tear fluid and eyeball surface, tear flow rates, and temperature should be optimized in further studies.
Scientific Presentations
2023
Garg P, Wulff D, Phan CM, Jones L. Evaluation of a biodegradable bioink for the fabrication of ophthalmic devices using 3D printing The Association for Research in Vision and Ophthalmology, New Orleans, LA, USA, April, 2023 [ Show Abstract ][ PDF ]
Purpose: To develop a degradable bioink for fabricating ophthalmic devices using 3D printing.
Methods: The bioink formulation consisted of 10% gelatin methacrylate (GelMA), 0.6% lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), and 5% yellow dye as a light absorbing agent to improve print resolution. The bioink was used to 3D print square sheets (7x7x1 mm) using a commercial masked-stereolithography (mSLA) 3D printer at 95% humidity and 37°C temperature. The degradation of printed sheets was evaluated with different concentrations (0,25,50,100 μg/ml) of matrix metalloproteinase (MMP9) enzyme 37°C. MMP9s are naturally found in the tear film and elevated in various diseased states such as in corneal wounds and dry eye disease. The weights of the sheets were measured at t = 0,4,6,8,12,16,24 hrs. Another set of cubes (1x1x1 cm) was autoclaved and kept sealed in storage at different temperatures (4°C, 25°C, and 37°C) in phosphate buffered saline (PBS) and their weight was measured on day 10. An attempt was made to fabricate a contact lens using this bioink.
Results: Samples that were exposed to MMP9 enzymes showed a time-dependent degradation with increasing enzyme concentration. The samples incubated with 100 and 50 μg/ml of MMP9 were completely degraded by the end of 12 and 16 hrs, respectively. At the end of 24 hrs, the samples incubated at 25 μg/ml enzyme showed 72.8% degradation whereas the control samples did not show any signs of degradation. Interestingly, samples that were autoclaved and kept in storage also did not show any signs of degradation at all temperatures. A 3D-printed CL with overall diameter 14mm and thickness 1mm was printed without any support structures within 1 hour.
Conclusion: This study showed GelMA-based bioink can be used to fabricate biodegradable devices such as contact lenses. The biomaterials degrade in the presence of MMP-9 and future work will work on tuning the degradation kinetics of these materials, as well as incorporating ocular drugs.
Garg P, Wulff D, Phan CM, Jones L. Fabrication of a degradable ocular drug delivery system using 3D printing CBB 2023 Conference: Waterloo for Health, Technology and Society, March, 2023 [ PDF ]
2022
Phan C-M, Wulff D, Garg P, Jones L.. Developing a novel in vitro eye model using 3D bioprinting for drug delivery studies The Association for Research in Vision and Ophthalmology, Denver, CO, USA, May 1, 2022 [ Show Abstract ]
Purpose: To develop an in vitro eye model using a novel 3D bioprinting method for testing the release of ophthalmic formulations to the posterior ocular region.
Methods: The eye model was designed using CAD software and includes both an anterior aqueous chamber and a posterior vitreous chamber. The vitreous chamber is surrounded by a blood chamber to mimic vessels that can be used to transport a blood-like substance. Three inlet ports control the flow of fluid into the chambers and the blood channels, and the three outlet ports allow fluids to exit these compartments. The eye model was 3D printed on a commercial mSLA printer (Photon Mono X, AnyCubic), which was retrofitted with a humidity and temperature control module to create a printing environment at 37°C and >80% humidity. The bioink formulation consisted of 10% gelatin methacrylate (GelMa). After printing, the models were incubated at 37°C to remove any uncured GelMa within any hollow compartments. For this study, phosphate-buffered saline was used as an aqueous and vitreous humour mimic. To evaluate the diffusion of a small hydrophilic molecule on the eye model, a contact lens (Air Optix) was soaked with a water-soluble red food dye for 1 hour and then placed on the eye model. The amount of dye in the anterior chamber, posterior chamber, and blood channels was measured using UV spectrophotometry after 24 hours.
Results: The entire model can be printed without any support structures within approximately 3 hours. The 3D printed eye model can also be autoclaved for testing that requires sterility. Because there were no diffusion barriers present in the current model, the red dye was detected in all three chambers after 24 hours. The highest concentration of dye was found in the anterior chamber, followed by the blood chamber and then the posterior chamber.
Conclusions: The prototype developed in this study can be used as a starting point to develop enhanced 3D printed eye models to test drug release kinetics of various devices and formulations. Future work will focus on adding the appropriate diffusion barriers to better simulate drug diffusion through ocular tissues.
Layman Abstract: The aim of the study was to create an advanced eye model using commercial 3D printing methods. Current 3D bioprinters are extremely expensive and regular commercial 3D printers do not have the capabilities to print biological materials. We are developing a method to 3D print sophisticated eye models using inexpensive 3D printers. The models from this research can further be refined for studying drug absorption in the eye. This research will also enable researchers to create their own biological models using 3D printing methods.
Professional Publications
2023
Garg P. Fast Forward to the Future: Biodegradable CLs Contact Lens Spectrum 2023;38, February:
