Dynamic versus static testing and in vivo mechanical performance of poly(glycolide-trimethylene carbonate-ε-caprolactone) delayed release implants.

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Tác giả: Tim R Dargaville, Dietmar W Hutmacher, Norman L Ilich, Siamak Saifzadeh

Ngôn ngữ: eng

Ký hiệu phân loại: 004.565 *Optical external storage

Thông tin xuất bản: Netherlands : Journal of controlled release : official journal of the Controlled Release Society , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 701643

The manufacturing of millimeter-sized implants for delayed drug release presents several challenges. However, it allows for the encapsulation of a therapeutic agent within a single device, enabling precise control over factors such as geometry, polymer composition, and drug formulation. The relatively large size, however, means that when inserted into subcutaneous tissue the implants experience mechanical stresses that are not predicted by current in vitro methods consisting of incubation under static conditions. The absence of a suitable in vitro assay complicates the device development process, often resulting in unsuccessful preclinical testing. This study presents the fabrication of flexible implants of poly(glycolide-co-trimethylene carbonate-co-ε-caprolactone), in vitro degradation, and performance when implanted subcutaneously in rats. Predicting the in vivo behaviour is addressed by the development of a scalable, high-throughput, cyclic flexural testing system. Flexural loading of the implant demonstrates a clear impact on loss in mechanical properties compared to static conditions in lipoprotein lipase. Under static conditions, a lag time of 60 days is observed before sustained release of the model dye. Conversely, the flexural loading assay results in early fracture by 20 days consistent with what is observed in the animal model. Decisively, this study emphasizes the importance of tailoring in vitro assays according to the dosage form and intended mode of administration. Implementation of a dynamic in vitro assay is invaluable to efficiently evaluate device viability and release kinetics and will, in turn, allow a more streamlined workflow for translation into preclinical models.
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