Motulsky Aude, Lafleur Michel, Couffin-Hoarau Anne-Claude, Hoarau Didier, Boury Frank, Benoit Jean-Pierre, Leroux Jean-Christophe
Canada Research Chair in Drug Delivery, Faculty of Pharmacy, University of Montreal, C.P. 6128 Succ. Centre-Ville, Montréal, Canada QC H3C 3J7.
Biomaterials. 2005 Nov;26(31):6242-53. doi: 10.1016/j.biomaterials.2005.04.004.
The development of simple and efficient drug delivery systems for the sustained release of peptides/proteins and low molecular weight hydrophilic molecules is an ongoing challenge. The purpose of this work was to prepare and characterize novel biodegradable in situ-forming implants obtained via the self-assembly of L-alanine derivatives in pharmaceutical oils. Six different amphiphilic organogelators based on L-alanine were synthesized. These derivatives could successfully gel various vegetable and synthetic oils approved for parenteral administration. Gelation was thermoreversible, and phase transition temperatures depended on gelator structure, concentration and solvent. Hydrogen bonds and van der Waals interactions were shown to be the main forces implicated in network formation. Selected formulations were then injected subcutaneously in rats for preliminary assessment of biocompatibility. Histopathological analysis of the surrounding tissues revealed mild, chronic inflammation and an overall good biocompatibility profile of the implants over the 8 wk evaluation period. This study demonstrates that in situ-forming organogels represent a potentially promising platform for sustained drug delivery.
开发用于肽/蛋白质和低分子量亲水性分子持续释放的简单高效药物递送系统是一项持续存在的挑战。这项工作的目的是制备并表征通过L-丙氨酸衍生物在药用油中自组装获得的新型可生物降解原位形成植入物。合成了六种基于L-丙氨酸的不同两亲性有机凝胶剂。这些衍生物能够成功地使各种批准用于肠胃外给药的植物油和合成油凝胶化。凝胶化是热可逆的，相变温度取决于凝胶剂的结构、浓度和溶剂。氢键和范德华相互作用被证明是参与网络形成的主要作用力。然后将选定的制剂皮下注射到大鼠体内，以初步评估生物相容性。对周围组织的组织病理学分析显示，在8周的评估期内，植入物有轻度慢性炎症且总体生物相容性良好。这项研究表明，原位形成有机凝胶是一种具有潜在前景的持续药物递送平台。
