Even Marie-Paule, Bobbala Sharan, Gibson Blake, Hook Sarah, Winter Gerhard, Engert Julia
Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-University Munich, Butenandtstr. 5, D-81377 Munich, Germany.
School of Pharmacy, University of Otago, PO Box 56, Dunedin 9054, New Zealand.
Eur J Pharm Biopharm. 2017 May;114:79-87. doi: 10.1016/j.ejpb.2016.12.033. Epub 2017 Jan 16.
Much effort has been put in the development of specific anti-tumour immunotherapies over the last few years, and several studies report on the use of liposomal carriers for tumour-associated antigens. In this work, the use of lipid implants, prepared using two different extruders, was investigated for sustained delivery in tumour therapy. The implants consisted of cholesterol, soybean lecithin, Dynasan 114, trehalose, ovalbumin (OVA) or a TRP2 peptide, and Quil-A. Implants were first produced on a Haake Minilab extruder, and then a scale-down to minimal quantities of material on a small scale ZE mini extruder was performed. All formulations were characterised in terms of extrudability, implant properties and in vitro release behaviour of the model antigen ovalbumin. The type of extruder used to produce the implants had a major influence on implant properties and the release behaviour, demonstrating that extrusion parameters and lipid formulations have to be individually adapted to each extrusion device. Subsequently, lipid implants containing TRP-2 peptide were extruded on the ZE mini extruder and investigated in vitro and in vivo. The in vivo study showed that mice having received TRP2 loaded implants had delayed tumour growth for 3days compared to groups having received no TRP2.
在过去几年中,人们在开发特异性抗肿瘤免疫疗法方面付出了巨大努力,并且有多项研究报道了脂质体载体用于肿瘤相关抗原的情况。在这项工作中,研究了使用两种不同挤出机制备的脂质植入物在肿瘤治疗中的持续递送情况。植入物由胆固醇、大豆卵磷脂、Dynasan 114、海藻糖、卵清蛋白(OVA)或TRP2肽以及Quil-A组成。植入物首先在哈克微型实验室挤出机上生产,然后在小型ZE微型挤出机上按比例缩小至最小量材料进行生产。所有制剂均根据可挤出性、植入物特性以及模型抗原卵清蛋白的体外释放行为进行了表征。用于生产植入物的挤出机类型对植入物特性和释放行为有重大影响,这表明挤出参数和脂质制剂必须针对每个挤出设备进行单独调整。随后,将含有TRP-2肽的脂质植入物在ZE微型挤出机上挤出,并进行体外和体内研究。体内研究表明,与未接受TRP2的组相比,接受负载TRP2植入物的小鼠肿瘤生长延迟了3天。