Shen Xin, Zhao Xinyu, McCoy Clare F, Dallal Bashi Yahya H, Boyd Peter, Malcolm R Karl
School of Pharmacy, Queen's University Belfast, Belfast, UK.
College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates.
Drug Deliv. 2025 Dec;32(1):2545515. doi: 10.1080/10717544.2025.2545515. Epub 2025 Aug 21.
Silicone elastomers based on polydimethylsiloxane are biocompatible and non-biodegradable thermosetting polymers used in various drug delivery applications, including subdermal implants, vaginal rings, and intrauterine devices. Without exception, all marketed silicone elastomer drug delivery products provide sustained or controlled release of highly hydrophobic small drug molecules, since drug solubility in the silicone matrix is a prerequisite for molecular diffusion and release. We are interested in developing multipurpose silicone elastomer vaginal rings for local administration of metal ions-such as copper and zinc-for non-hormonal contraception and antimicrobial therapy. However, sustained/controlled release of metal ions from silicone elastomers containing metal nanopowders or metal salts is challenging due to their limited solubility in silicone. In this study, we assess the potential for enhancing the release of copper or zinc ions from silicone elastomer devices by co-formulating copper nanopowder, zinc nanopowder, copper sulfate, or zinc acetate with four common pharmaceutical excipients-gelatin, polyvinylpyrrolidone, sucrose, and hydroxypropyl methylcellulose. The study demonstrates that (i) copper/zinc nanopowders and salts can be successfully incorporated into addition-cure silicone elastomers, (ii) release of Cu/Zn ions from silicone elastomers loaded with divalent salts was ∼100 times greater compared to nanopowders; (iii) incorporation of gelatin, polyvinylpyrrolidone, sucrose and hydroxypropyl methylcellulose significantly enhanced the release of Cu/Zn ions (up to ∼30-fold), and (iv) enhanced release was due to water absorption into the silicone elastomer devices, causing swelling of the devices to an extent proportional to the excipient loading.
基于聚二甲基硅氧烷的硅橡胶是生物相容性且不可生物降解的热固性聚合物，用于各种药物递送应用，包括皮下植入物、阴道环和宫内节育器。毫无例外，所有市售的硅橡胶药物递送产品都能实现高度疏水的小药物分子的持续或控释，因为药物在硅橡胶基质中的溶解性是分子扩散和释放的先决条件。我们有兴趣开发用于局部施用金属离子（如铜和锌）的多功能硅橡胶阴道环，用于非激素避孕和抗菌治疗。然而，由于金属纳米粉末或金属盐在硅橡胶中的溶解度有限，从含有它们的硅橡胶中持续/控释金属离子具有挑战性。在本研究中，我们评估了通过将铜纳米粉末、锌纳米粉末、硫酸铜或醋酸锌与四种常见的药用辅料（明胶、聚乙烯吡咯烷酮、蔗糖和羟丙基甲基纤维素）共配制来提高硅橡胶装置中铜或锌离子释放的潜力。该研究表明：（i）铜/锌纳米粉末和盐可以成功地掺入加成型固化硅橡胶中；（ii）与纳米粉末相比，负载二价盐的硅橡胶中铜/锌离子的释放量大约高100倍；（iii）加入明胶、聚乙烯吡咯烷酮、蔗糖和羟丙基甲基纤维素显著提高了铜/锌离子的释放（高达约30倍）；（iv）释放增强是由于水被吸收到硅橡胶装置中，导致装置膨胀，膨胀程度与辅料负载量成正比。
