Secant Group, LLC. Telford, PA, USA.
Expert Opin Drug Deliv. 2023 Feb;20(2):285-299. doi: 10.1080/17425247.2023.2168642. Epub 2023 Jan 18.
Poly(glycerol sebacate) urethane (PGSU) elastomers formulated with 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA), levonorgestrel (LNG), or a combination thereof can function as multipurpose prevention technology implants for prophylaxis against HIV and unintended pregnancies. For these public health challenges, long-acting drug delivery technologies may improve patient experience and adherence. Traditional polymers encounter challenges delivering multiple drugs with dissimilar physiochemical properties. PGSU offers an alternative option that successfully delivers hydrophilic EFdA alongside hydrophobic LNG.
This article presents the formulation, design, and characterization of PGSU implants, highlighting the impact of API loading, dimensions, and individual- versus combination-loading on release rates.
Co-delivery of hydrophilic EFdA alongside hydrophobic LNG acted as a porogen to accelerate LNG release. Increasing the surface area of LNG-only implants increased LNG release. All EFdA-LNG, EFdA-only, and LNG-only formulated implants demonstrated low burst release and linear release kinetics over 245 or 122 days studied to date.
PGSU co-delivers two APIs for HIV prevention and contraception at therapeutically relevant concentrations from a single bioresorbable, elastomeric implant. A new long-acting polymer technology, PGSU demonstrates linear-release kinetics, dual delivery of APIs with disparate physiochemical properties, and biocompatibility through long-term subcutaneous implantation. PGSU can potentially meet the demands of complex MPT or fixed-dose combination products, where better solutions can serve and empower patients.
聚（癸二酸丙二醇酯）氨酯（PGSU）弹性体与 4′-乙炔基-2-氟-2′-脱氧腺苷（EFdA）、左炔诺孕酮（LNG）或两者的组合可以作为预防 HIV 和意外怀孕的多用途预防技术植入物。对于这些公共卫生挑战，长效药物输送技术可能会改善患者的体验和依从性。传统聚合物在输送具有不同物理化学性质的多种药物时会遇到挑战。PGSU 提供了一种替代方案，可以成功输送亲水性 EFdA 以及疏水性 LNG。
本文介绍了 PGSU 植入物的配方、设计和特性，重点介绍了 API 载药量、尺寸以及单一和组合载药对释放速率的影响。
亲水性 EFdA 与疏水性 LNG 共载药起到了致孔剂的作用，加速了 LNG 的释放。增加仅含 LNG 植入物的表面积增加了 LNG 的释放。迄今为止研究的 245 或 122 天内，所有含 EFdA-LNG、EFdA 仅和 LNG 仅的配方植入物均表现出低突释和线性释放动力学。
PGSU 从单个可生物吸收的弹性植入物中以治疗相关浓度共同输送两种用于 HIV 预防和避孕的 API。一种新的长效聚合物技术 PGSU 展示了线性释放动力学、具有不同物理化学性质的 API 的双重输送以及通过长期皮下植入的生物相容性。PGSU 有可能满足复杂 MPT 或固定剂量组合产品的需求，为患者提供更好的解决方案。
