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硼替佐米负载聚甲基丙烯酸甲酯涂层髓内钉的化疗药物释放:一种用于局部化疗给药装置的新型体外研究。

Chemotherapy Release From Bortezomib-Impregnated Polymethylmethacrylate-Coated Intramedullary Nails: A Novel In Vitro Study for a Local Chemotherapy Delivery Device.

作者信息

Ren Emily, Ren Weiping, Collins Angela C, Robinson Andrew, Vaidya Rahul

机构信息

Department of Orthopaedic Surgery, Wayne State University Detroit Medical Center, Detroit, USA.

Department of Biomedical Engineering, Wayne State University, Detroit, USA.

出版信息

Cureus. 2024 Jul 9;16(7):e64181. doi: 10.7759/cureus.64181. eCollection 2024 Jul.

Abstract

Bortezomib (BAN) is a proteasome inhibitor approved for the treatment of multiple myeloma and lymphoma. Despite its efficacy in various tumor models, systemic administration can result in toxicity to healthy organs. The purpose of this study is to evaluate the elution profile of BAN from PMMA cement for the local treatment of orthopedic tumors. BAN solution (5 mg; 2 mg/mL) was mixed with Simplex cement (40 g, Stryker), followed by injection of cement into an antibiotic cement nail mold (13 mm) to coat a 10 mm titanium femoral nail (DePuy Synthes). Once the cement polymerized, the nail was cut into 2 cm segments for the BAN elution study. There is a sustained release of BAN for up to 28 days. The overall concentration of BAN released at each time point was between 74 and 263 ng/ml, which is compatible with the peak blood concentration of a single intravenous BAN injection. This study demonstrates the feasibility of using PMMA bone cement as a local BAN delivery tool, essential for future studies and treatment targeting multiple myeloma cells.

摘要

硼替佐米(BAN)是一种蛋白酶体抑制剂,已被批准用于治疗多发性骨髓瘤和淋巴瘤。尽管它在各种肿瘤模型中都有效,但全身给药会对健康器官产生毒性。本研究的目的是评估硼替佐米从聚甲基丙烯酸甲酯(PMMA)骨水泥中的洗脱情况,用于骨科肿瘤的局部治疗。将硼替佐米溶液(5毫克;2毫克/毫升)与Simplex骨水泥(40克,史赛克公司)混合,然后将骨水泥注入抗生素骨水泥钉模具(13毫米)中,以包裹一根10毫米的钛制股骨钉(德普伊辛普利斯公司)。骨水泥聚合后,将钉子切成2厘米长的段进行硼替佐米洗脱研究。硼替佐米可持续释放长达28天。每个时间点释放的硼替佐米总浓度在74至263纳克/毫升之间,这与单次静脉注射硼替佐米的峰值血药浓度相符。本研究证明了使用PMMA骨水泥作为局部递送硼替佐米工具的可行性,这对未来针对多发性骨髓瘤细胞的研究和治疗至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/870d/11309748/3a2fe44ddff9/cureus-0016-00000064181-i01.jpg

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