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

IF 3.6 4区 医学 Q2 ENGINEERING, BIOMEDICAL
Victor de Carvalho Rodrigues, Iara Zanella Guterres, Beatriz Pereira Savi, Gislaine Fongaro, Izabella Thaís Silva, Gean Vitor Salmoria
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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.

用于持续释放阿昔洛韦治疗生殖器疱疹的热塑性聚氨酯设备的添加剂制造。
治疗复发性生殖器疱疹通常需要每天长期服用阿昔洛韦。增材制造是一种令人感兴趣的技术,可用于创建个性化给药系统,从而提高各种疾病的治疗效果。阴道给药途径为口服生物利用度较低的全身给药提供了一种可行的替代方法。在这项研究中,我们通过热熔挤出法生产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%。我们利用熔融长丝制造技术制造了基于基质的装置,包括宫内装置和阴道内环。我们通过扫描电镜、傅立叶变换红外光谱和 DSC 分析获得的结果证实,阿昔洛韦成功地融入了基质中。热分析表明,制造过程改变了热塑性聚氨酯链的组织结构,导致结晶度略有降低。在体外测试中,我们观察到了第一天的初始迸发释放,随后以较低的速率持续释放长达 145 天,这证明了其长期应用的潜力。此外,细胞毒性分析表明,这种印刷设备具有良好的生物相容性,生物试验显示,HSV-1 复制率显著降低了 99%。总之,热塑性聚氨酯印刷设备为生殖器疱疹的长期治疗提供了一种前景广阔的替代方案,所取得的成果有望推动药品生产的发展。
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来源期刊
Journal of Biomaterials Science, Polymer Edition
Journal of Biomaterials Science, Polymer Edition 工程技术-材料科学:生物材料
CiteScore
7.10
自引率
5.60%
发文量
117
审稿时长
1.5 months
期刊介绍: The Journal of Biomaterials Science, Polymer Edition publishes fundamental research on the properties of polymeric biomaterials and the mechanisms of interaction between such biomaterials and living organisms, with special emphasis on the molecular and cellular levels. The scope of the journal includes polymers for drug delivery, tissue engineering, large molecules in living organisms like DNA, proteins and more. As such, the Journal of Biomaterials Science, Polymer Edition combines biomaterials applications in biomedical, pharmaceutical and biological fields.
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