Characterization for In-situ Ocular Implant Formation




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Different diseases of the eye require intravitreal injections for treatment. While intravitreal injections are quick procedures, their requirement for routine in-office visits makes them inconvenient. An alternative is intra-ocular implants, designed to stay within the eye, these allow controlled release of therapeutic drugs to the posterior segment of the eye. Intra-ocular implants require symmetrical shapes for even and steady release of the drug. To study how well in-situ implants form, vitreous humor substitutes were made using varying ratios of hyaluronic acid (HA) and polyvinyl alcohol (PVA) within phosphate-buffered saline (PBS). These substitutes have surface characteristics that can be used as a potential marker to predict how symmetrical the in-situ implant forms. Here, we use contact angles to help characterize their interaction.


Vitreous humor substitutes were made using 0.01 g/mL solutions of HA and PVA in PBS. These solutions were mixed to create the following ratios of HA:PVA: 1:3, 1:1, and 3:1. To make the implant, 1-Methyl-2-pyrrolidone was dissolved in polylactic-co-glycolic acid in a 1.96:1 ratio. Films were prepared on glass slides using the solutions to take contact angles of the implant. Contact angles were taken using an optical goniometer at 30.2 frames per second for 10 seconds, where it was set to dispense 2 µL each time. For in-situ implant formation, the implant was injected into 5 mL wells of each solution (PBS, HA, PVA, 1:3, 1:1, and 3:1) at a 90-degree angle using a 20 gauge needle at 1.2 cm deep. In-situ implant formation was repeated 4 times.


The following contact angles were taken at frame 300 and are the average of at least 10 runs. The average contact angle for water on a plain glass slide and the implant on a plain glass slide, PVA film, 1:3 film, 1:1 film, 3:1 film, and on the HA film was 26.13 ± 3.79, 28.57 ± 2.29, 32.65 ± 5.75, 32.41 ± 4.21, 35.02 ± 3.03, 37.20 ± 4.92, and 40.71 ± 5.22 degrees respectively. In-situ implant formation was consistently the most symmetrical within HA and the 1:3 hybrid, though still in irregular yet compact shapes. In-situ implant formations within the other solutions were randomly shaped with tendrilous protrusions that would coil upon themselves.


Contact angles for all solutions were found to be statistically different using T-tests. The different contact angles allow us to manipulate the interactions by varying the ratio of HA and PVA to make an environment most suitable for intra-ocular implant formation. Interestingly, the 1:3 substitute did not follow the direct relationship found between the amount of HA present in each vitreous humor substitute and their contact angles. Despite having one of the least amounts of HA, it provided a better environment for implant formulation. Thus, there must be an interaction between HA, PVA, and the implant that is optimal at 1:3. More is to be done with the 1:3 hybrid and implant by repeating the experiment with serial dilutions to help us determine which patient populations may be most suitable to this type of treatment.