Institute of Ocular Pharmacology, School of Ophthalmology and Optometry, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou, Zhejiang 325027, China; Institute of Brain Science, School of Medicine, Shanxi Datong University, Datong, Shanxi 037009, China.
Institute of Ocular Pharmacology, School of Ophthalmology and Optometry, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou, Zhejiang 325027, China.
Acta Biomater. 2016 Jun;37:143-54. doi: 10.1016/j.actbio.2016.04.014. Epub 2016 Apr 9.
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 (86days versus 43days). 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.
This 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.
将曲安奈德（TA）和聚己内酯（PCL）制成微药物膜，用于巩膜给药，以更好地治疗慢性眼后段疾病，如增生性玻璃体视网膜病变（PVR）。与玻璃体内药物注射相比，这种药物膜更安全，不会穿透眼内屏障。与传统的球周注射相比，这种药物膜具有更长的治疗持续时间、更好的药物在脉络膜和视网膜中的生物利用度，以及更好的靶向药物递送能力。兔眼研究表明，与球周注射相比，使用 PCL-TA 膜可使脉络膜和视网膜中的药物 AUC 分别增加 5.6 倍和 3.4 倍。使用巩膜 TA 膜还使兔脉络膜中的药物滞留时间增加了一倍（86 天与 43 天）。药物膜中剩余的 TA 始终高于球周间隙中的 TA，表明 PCL-TA 膜可控制 TA 的释放。通过使用这种膜，将曲安奈德在脉络膜和视网膜中的药代动力学从典型的一级动力学优化为更持续的释放。这种巩膜膜系统在兔眼上的效果优于豚鼠眼，表明巩膜厚度和眼睛大小可能是选择动物模型或设计用于人类的经巩膜递药装置时需要考虑的关键方面。这种工程化的药物膜在预防和治疗与开放性眼外伤或视网膜脱离手术修复相关的 PVR 方面可能非常有用。
本研究展示了一种新型的微巩膜药物膜，它是由曲安奈德（TA）工程化到聚己内酯（PCL）中制成的。该膜可在初次手术时方便地放置在损伤或病变部位，提供长达四个月的 TA 控释，覆盖了发生增生性玻璃体视网膜病变（PVR）的高风险时间窗。这种工程化的药物膜在预防和治疗与开放性眼外伤或眼内手术相关的 PVR 方面可能非常有用。
