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用于持续释放阿昔洛韦治疗生殖器疱疹的热塑性聚氨酯(TPU)装置的增材制造。

Additive manufacturing of TPU devices for genital herpes treatment with sustained acyclovir release.

作者信息

de Carvalho Rodrigues Victor, Guterres Iara Zanella, Pereira Savi Beatriz, Fongaro Gislaine, Silva Izabella Thaís, Vitor Salmoria Gean

机构信息

Nimma, Department of Mechanical Engineering, Federal University of Santa Catarina, Florianópolis, Brazil.

Laboratory of Applied Virology, Department of Microbiology, Immunology and Parasitology, Federal University of Santa Catarina, Florianópolis, Brazil.

出版信息

J Biomater Sci Polym Ed. 2024 Aug 27:1-16. doi: 10.1080/09205063.2024.2396221.

Abstract

The treatment of recurrent genital herpes typically involves daily doses of acyclovir for extended periods. Additive manufacturing is an intriguing technique for creating personalised drug delivery systems, which can enhance the effectiveness of treatments for various diseases. The vaginal route offers a viable alternative for the systemic administration of drugs with low oral bioavailability. In this study, we produced different grades of thermoplastic polyurethane (TPU) filaments through hot-melt extrusion, with acyclovir concentrations of 0%, 10%, and 20% by weight. We used fused filament fabrication to manufacture matrix-based devices, including intrauterine devices and intravaginal rings. Our results, obtained through SEM, FTIR, and DSC analyses, confirm the successful incorporation of acyclovir into the matrix. Thermal analysis reveals that the manufacturing process alters the organization of the TPU chains, resulting in a slight reduction in crystallinity. In our in-vitro tests, we observed an initial burst release on the first day, followed by sustained release at reduced rates for up to 145 days, demonstrating their potential for long-term applications. Additionally, cytotoxicity analysis suggests the excellent biocompatibility of the printed devices, and biological assays show a remarkable 99% reduction in HSV-1 replication. In summary, TPU printed devices offer a promising alternative for long-term genital herpes treatment, with the results obtained potentially contributing to the advancement of pharmaceutical manufacturing.

摘要

复发性生殖器疱疹的治疗通常需要长时间每日服用阿昔洛韦。增材制造是一种用于创建个性化给药系统的有趣技术,可提高各种疾病治疗的有效性。对于口服生物利用度低的药物,阴道途径为全身给药提供了一种可行的替代方法。在本研究中,我们通过热熔挤出制备了不同等级的热塑性聚氨酯(TPU)长丝,阿昔洛韦的重量浓度分别为0%、10%和20%。我们使用熔融长丝制造法制造基于基质的装置,包括宫内装置和阴道环。通过扫描电子显微镜(SEM)、傅里叶变换红外光谱(FTIR)和差示扫描量热法(DSC)分析获得的结果证实阿昔洛韦已成功掺入基质中。热分析表明,制造过程改变了TPU链的排列,导致结晶度略有降低。在我们的体外试验中,可以观察到第一天有初始的突释,随后以降低的速率持续释放长达145天,这表明它们具有长期应用的潜力。此外,细胞毒性分析表明打印装置具有出色的生物相容性,生物学试验显示单纯疱疹病毒1型(HSV-1)复制显著减少99%。总之,TPU打印装置为生殖器疱疹的长期治疗提供了一种有前景的替代方法,所获得的结果可能有助于推进药物制造技术的发展。

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