Episcleral drug film for better-targeted ocular drug delivery and controlled release using multilayered poly-ε-caprolactone (PCL)
Triamcinolone acetonide (TA) and poly-ε-caprolactone (PCL) were engineered into a micro drug film for episcleral application to better manage chronic vitreoretinal diseases such as proliferative vitreoretinopathy (PVR). Compared to an intravitreal drug injection, this drug film is much safer without breaking into ocular barriers. Compared to a traditional subtenon injection, this drug film demonstrated superior therapeutic duration, better drug bioavailability in the choroid and retina, and better-targeted drug delivery ability. The rabbit eye study demonstrated that using the PCL-TA film led to 5.6 and 3.4 times higher drug AUC in the choroid and the retina respectively than in eyes following a subtenon drug injection. The mean drug residence time in the rabbit choroid was also doubled by using the episcleral TA film (86 days versus 43 days). Remaining TA in the drug film was consistently higher than that in the subtenon space, indicating controlled release of TA by the PCL-TA film. The pharmacokinetics of triamcinolone in the choroid and retina were optimized from typical first-order kinetics to a more sustained release by use of this film. This episcleral film system worked better on rabbit eyes than on guinea pig eyes, indicating that scleral thickness and eye size may be crucial aspects to consider when choosing an animal model or when designing a transscleral delivery device for human use. This engineered drug film may be very useful in preventing and managing PVR associated with open globe trauma or surgical repair for retinal detachment.Statement of SignificanceThis study demonstrated a novel micro episcleral drug film that is made from the engineering of triamcinolone acetonide (TA) into poly-ε-caprolactone (PCL). The film can be conveniently placed at the injury or disease site during primary surgery and provide controlled release of TA for four months that covers the high-risk time window for developing proliferative vitreoretinopathy (PVR). This engineered drug film may be very useful in preventing and managing PVR associated with open globe trauma or intraocular surgery.
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Journal: Acta Biomaterialia - Volume 37, June 2016, Pages 143–154