School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Acta Biomater. 2018 Feb;67:99-110. doi: 10.1016/j.actbio.2017.11.057. Epub 2017 Dec 8.
Local anesthetics have been widely used for postoperative analgesia. However, multiple injections or local infiltration is required due to the short half-lives of local anesthetics after single injection, which results in poor compliance and increasing medical expense. In this study, an in situ forming gel (ISFG) based on lyotropic liquid crystal was developed to deliver bupivacaine hydrochloride (BUP) for long-acting postoperative analgesia. BUP-ISFG was designed to be administrated as a precursor solution which would spontaneously transform into gel with well-defined internal nanostructures for sustained drug release at the site of administration when exposed to physiological fluid. A lamellar-hexagonal-cubic phase transition occurred during the in situ gelation. The lamellar phase of the precursor solution endows it with low viscosity for good syringeability while the unique nanostructures of hexagonal and cubic phases of the in situ gel provide sustained drug release. Persistent analgesia effect in vivo was achieved with BUP-ISFG, and the plasma BUP concentration was found to be steadier compared to commercially available BUP for injection. In addition, the ISFG displayed acceptable biocompatibility and good biodegradability. The findings are positive about ISFG as a sustained release system for persistent postoperative analgesia.
To address the issue of insufficient postoperative analgesia associated with short half-lives of local anesthetics after single injection, an in situ forming gel (ISFG) based on lyotropic liquid crystal was developed to deliver bupivacaine hydrochloride (BUP) for postoperative analgesia over three days. The results demonstrated that persistent analgesia effect in vivo was achieved with single injection of BUP-ISFG, and the plasma BUP concentration was found to be steadier compared to commercially available BUP injection. The BUP-ISFG possessed a lamellar-hexagonal-cubic phase transition with corresponding crystal change in 3D nanostructure during the in situ gelation. The relationship between crystal nanostructure and carrier function, might provide some insights to the design and clinical applications of the drug delivery systems based on lyotropic liquid crystal.
局部麻醉剂已广泛用于术后镇痛。然而，由于单次注射后局部麻醉剂的半衰期较短，需要多次注射或局部浸润，导致患者顺应性差且医疗费用增加。本研究开发了一种基于溶致液晶的原位形成凝胶（ISFG），以递送盐酸布比卡因（BUP）用于长效术后镇痛。BUP-ISFG 设计为前体溶液给药，当暴露于生理流体时，前体溶液会自发转化为具有明确定义的内部纳米结构的凝胶，从而在给药部位实现药物的持续释放。原位凝胶化过程中发生层状-六方-立方相转变。前体溶液的层状相使其具有低粘度，有利于注射器给药，而原位凝胶的六方相和立方相的独特纳米结构提供了药物的持续释放。BUP-ISFG 实现了体内持久的镇痛效果，与市售的注射用布比卡因相比，BUP 的血浆浓度更稳定。此外，ISFG 表现出良好的生物相容性和可生物降解性。这些发现表明，ISFG 作为一种用于持续术后镇痛的缓释系统具有积极意义。
