Poloxamer 407/188 binary thermosensitive hydrogels as delivery systems for infiltrative local anesthesia: Physico-chemical characterization and pharmacological evaluation
Poloxamer 407/188 binary thermosensitive hydrogels as delivery systems for infiltrative local anesthesia: Physico-chemical characterization and pharmacological evaluation
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DOI：
10.1016/j.msec.2016.05.088
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发表时间：
2016-11-01
影响因子：
7.9
通讯作者：
de Araujo, Daniele R.
中科院分区：
文献类型：
--
作者：
Akkari, Alessandra C. S.;Boava Papini, Juliana Z.;de Araujo, Daniele R.
在这项研究中，我们报道了泊洛沙姆 407 (PL407) 和泊洛沙姆 188 (PL188) 二元系统作为水凝胶用于输送罗哌卡因 (RVC) 的开发和物理化学表征，作为药物模型，并研究了它们在浸润性局部麻醉中用于治疗术后疼痛的应用。我们通过光散射和差示扫描量热法 (DSC) 研究药物-胶束相互作用和胶束化过程，通过小角 X 射线散射 (SAXS) 研究溶胶-凝胶转变和水凝胶超分子结构，并通过扫描电子显微镜 (SEM) 进行形态评估。此外，我们还介绍了药物释放机制、体外/体内毒性和镇痛作用的研究。胶束尺寸评估显示 PL407-PL188 混合胶束的形成和药物掺入，DSC 研究显示添加 PL 188 和 RVC 后胶束形成的焓值增加，表明药物掺入引起的自组装和混合胶束形成的变化。 SAXS 研究表明，六方结构中的相组织不受 RVC 插入水凝胶的影响，保持了其超分子结构。添加 RVC 后，SEM 分析显示出类似的模式。 RVC 的释放遵循 Higuchi 模型，由 PL 终浓度和 PL 188 插入系统进行调节。此外，在单剂量模型研究中，PL407-PL188 的联合诱导了较低的体外细胞毒性作用，增加了镇痛持续时间，且局部注射后不会引起体内炎症症状。 (C) 2016 Elsevier B.V. 保留所有权利。
In this study, we reported the development and the physico-chemical characterization of poloxamer 407 (PL407) and poloxamer 188 (PL188) binary systems as hydrogels for delivering ropivacaine (RVC), as drug model, and investigate their use in infiltrative local anesthesia for applications on the treatment of post-operative pain. We studied drug-micelle interaction and micellization process by light scattering and differential scanning calorimetry (DSC), the sol-gel transition and hydrogel supramolecular structure by small-angle-X-ray scattering (SAXS) and morphological evaluation by Scanning Electron Microscopy (SEM). In addition, we have presented the investigation of drug release mechanisms, in vitro/in vivo toxic and analgesic effects. Micellar dimensions evaluation showed the formation of PL407-PL188 mixed micelles and the drug incorporation, as well as the DSC studies showed increased enthalpy values for micelles formation after addition of PL 188 and RVC, indicating changes on self-assembly and the mixed micelles formation evoked by drug incorporation. SAXS studies revealed that the phase organization in hexagonal structure was not affected by RVC insertion into the hydrogels, maintaining their supramolecular structure. SEM analysis showed similar patterns after RVC addition. The RVC release followed the Higuchi model, modulated by the PL final concentration and the insertion of PL 188 into the system. Furthermore, the association PL407-PL188 induced lower in vitro cytotoxic effects, increased the duration of analgesia, in a single-dose model study, without evoking in vivo inflammation signs after local injection. (C) 2016 Elsevier B.V. All rights reserved.