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载唑来膦酸的生物材料的开发用于增强引导性骨再生。

Development of Zoledronic Acid Containing Biomaterials for Enhanced Guided Bone Regeneration.

机构信息

Faculty of Pharmacy Department of Pharmaceutical Technology, Ankara University, Ankara, Turkey.

Faculty of Pharmacy Department of Pharmaceutical Technology, Ankara University, Ankara, Turkey.

出版信息

J Pharm Sci. 2021 Sep;110(9):3200-3207. doi: 10.1016/j.xphs.2021.05.002. Epub 2021 May 11.

Abstract

In recent years, biomaterial-based treatments, also called guided bone regeneration (GBR), which aim to establish a bone regeneration site and prevent the migration of gingival connective tissue and / or peripheral epithelium through the defective area during periodontal surgical procedures have come to the fore. In this report, we have developed a nanoparticle bearing thermosensitive in situ gel formulation of Pluronic F127 and poly(D,L-lactic acid) based membrane to reveal their utilization at GBR by in-vivo applications. In addition, the encouragement of the bone formation in defect area via inhibition of osteoclastic activity is intended by fabrication these biodegradable biomaterials at a lowered Zoledronic Acid (ZA) dose. Both of the developed materials remained stable under specified stability conditions (25 °C, 6 months) and provided the extended release profile of ZA. The in-vivo efficacy of nanoparticle bearing in situ gel formulation, membrane formulation and simultaneous application for guided bone regeneration was investigated in New Zealand female rabbits with a critical size defect of 0.5 × 0.5 cm in the tibia bone for eight weeks. Based on the histopathological findings, lamellar bone and primarily woven bone formations were observed after 8 weeks of post-implantation of both formulations, while fibrosis was detected only in the untreated group. Lamellar bone growth was remarkably achieved just four weeks after the simultaneous application of formulations. Consequently, the simultaneous application of ZA-membrane and ZA-nanoparticles loaded in-situ gel formulations offers enhanced and faster GBR therapy alternatives.

摘要

近年来,基于生物材料的治疗方法,也称为引导骨再生(GBR),旨在建立骨再生部位,并防止牙周手术过程中缺陷区域的牙龈结缔组织和/或周围上皮迁移。在本报告中,我们开发了一种载有热敏原位凝胶制剂的纳米粒子,该制剂由 Pluronic F127 和聚(D,L-乳酸)组成的膜,通过体内应用揭示其在 GBR 中的应用。此外,通过降低唑来膦酸(ZA)剂量制造这些可生物降解的生物材料,旨在通过抑制破骨细胞活性来鼓励缺陷区域的骨形成。两种开发的材料在特定的稳定性条件(25°C,6 个月)下保持稳定,并提供 ZA 的延长释放曲线。载有原位凝胶制剂、膜制剂和同时应用于引导骨再生的纳米粒子的体内功效在新西兰雌性兔中进行了研究,在胫骨中有 0.5×0.5cm 的临界尺寸缺陷,持续 8 周。根据组织病理学发现,两种制剂植入后 8 周观察到板层骨和主要编织骨形成,而未治疗组仅检测到纤维化。两种制剂同时应用后仅四周就明显实现了板层骨生长。因此,ZA 膜和载有 ZA 的纳米粒子原位凝胶制剂的同时应用提供了增强和更快的 GBR 治疗替代方案。

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