Univ. Lille, Inserm, CHU Lille, U1008 - Controlled Drug Delivery Systems and Biomaterials, F-59000 Lille, France.
Univ. Lille, Inserm, CHU Lille, U1008 - Controlled Drug Delivery Systems and Biomaterials, F-59000 Lille, France.
Int J Pharm. 2017 Apr 15;521(1-2):282-293. doi: 10.1016/j.ijpharm.2017.02.039. Epub 2017 Feb 20.
In-situ forming implants (ISFI) offer an interesting potential for the treatment of periodontitis, allowing for time-controlled drug release directly at the site of action (which is difficult to reach). For this purpose, ISFI loaded with antibiotics have been reported in the literature. But the use of antibiotic drugs at low doses over prolonged periods of time can lead to the development of bacterial resistances. This risk should be avoided. The aim of this study was to develop a novel type of in-situ forming implants, loaded with the antiseptic drug chlorhexidine. Special emphasis was placed on the physical properties of the systems, assuring a reliable residence time in the periodontal pockets of patients suffering from periodontitis. In particular, the risk of premature, accidental loss of the formulations due to mechanical stress (e.g. during tooth brushing and chewing) was to be reduced. Two commercially available drug products for local periodontitis treatment were studied for reasons of comparison: Chlo-site and Parocline. The syringeability and swelling behavior of the formulations were investigated, and the hardness, springiness, resilience and "stickiness" of the systems determined using extracted human teeth. Interestingly, the novel in-situ forming implants, based on PLGA/HPMC and being free of antibiotics, exhibit highly promising physical key properties: They are intensively sticking to teeth' surfaces and provide adequate mechanical strength to assure reliable and prolonged residence times in periodontal pockets. In contrast, the commercial drug products showed limited adhesion and either rapidly shrank (Chlo-site), or substantially swelled and were mechanically very weak (Parocline).
原位形成植入物（ISFI）为治疗牙周炎提供了一个有趣的潜力，允许在作用部位（难以到达）进行时间控制的药物释放。为此，文献中报道了载有抗生素的 ISFI。但是，长时间低剂量使用抗生素药物会导致细菌产生耐药性。这个风险应该避免。本研究的目的是开发一种新型的原位形成植入物，负载抗菌药物洗必泰。特别强调了系统的物理性质，以确保在患有牙周炎的患者的牙周袋中具有可靠的停留时间。特别是，由于机械应力（例如刷牙和咀嚼时），制剂过早，意外损失的风险（例如刷牙和咀嚼时）要降低。出于比较的原因，研究了两种市售的局部牙周炎治疗药物产品：Chlo-site 和 Parocline。研究了制剂的可注射性和溶胀行为，并使用提取的人牙确定了系统的硬度，弹性，回弹性和“粘性”。有趣的是，基于 PLGA/HPMC 的新型原位形成植入物不含抗生素，具有非常有前途的物理关键性能：它们强烈粘附在牙齿表面上，并提供足够的机械强度，以确保在牙周袋中可靠且长时间停留。相比之下，商业药物产品的粘附性有限，要么迅速收缩（Chlo-site），要么大量肿胀且机械强度非常弱（Parocline）。
