Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, Tokushima, Japan.
Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, Tokushima, Japan; Formulation Research Laboratory, CMC Division, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
Int J Biol Macromol. 2021 Mar 31;174:494-501. doi: 10.1016/j.ijbiomac.2021.01.201. Epub 2021 Feb 2.
Nano-fibrillated bacterial cellulose (NFBC) is a safe, biocompatible material that can be prepared by culturing a cellulose-producing bacterium in a culture supplemented with carboxymethylcellulose (CMC) or hydroxypropylcellulose (HPC). CM-NFBC and HP-NFBC, prepared using CMC or HPC, show hydrophilicity and amphiphilicity, respectively, and thus they could be useful carriers for hydrophobic anticancer agents such as paclitaxel (PTX). In the present study, we prepared novel PTX formulations for intraperitoneal administration by associating PTX with either CM-NFBC or HP-NFBC and studied their therapeutic efficacy on peritoneally disseminated gastric cancer in a xenograft nude mouse model. Freeze-dried PTX formulations (PTX/CM-NFBC and PTX/HP-NFBC) were quickly reconstituted with saline without any foaming, compared to nanoparticle albumin-bound PTX (nab-PTX, Abraxane®). Both PTX/NFBC formulations extended the mean survival times in our xenograft murine models compared with either free PTX or nab-PTX. The PTX/NFBC formulations reduced systemic side effects of free PTX relating to weight loss. In our disseminated gastric peritoneal cancer model, the PTX/NFBC formulation increased the therapeutic index for PTX by increasing the therapeutic efficacy and decreasing toxicity. NFBCs should receive consideration as improved carriers for the clinical delivery of hydrophobic anticancer drugs such as PTX in malignancies in the abdominal cavity with peritoneal metastasis and dissemination.
纳米原纤化细菌纤维素（NFBC）是一种安全、生物相容的材料，可以通过在含有羧甲基纤维素（CMC）或羟丙基纤维素（HPC）的培养基中培养产纤维素细菌来制备。使用 CMC 或 HPC 制备的 CM-NFBC 和 HP-NFBC 分别表现出亲水性和两亲性，因此它们可以作为疏水性抗癌药物（如紫杉醇（PTX））的有用载体。在本研究中，我们通过将 PTX 与 CM-NFBC 或 HP-NFBC 结合，制备了用于腹腔内给药的新型 PTX 制剂，并在异种移植裸鼠模型中研究了它们对腹膜播散性胃癌的治疗效果。与白蛋白结合型紫杉醇（nab-PTX，Abraxane®）相比，冻干的 PTX 制剂（PTX/CM-NFBC 和 PTX/HP-NFBC）在与生理盐水复溶时不会产生泡沫。与游离 PTX 或 nab-PTX 相比，两种 PTX/NFBC 制剂均延长了我们异种移植小鼠模型的平均存活时间。PTX/NFBC 制剂减轻了游离 PTX 引起的体重减轻等全身副作用。在我们的腹膜播散性胃癌模型中，PTX/NFBC 制剂通过提高治疗效果和降低毒性，提高了 PTX 的治疗指数。NFBC 应该被视为改善载体，用于临床输送疏水性抗癌药物，如 PTX，治疗腹腔内伴腹膜转移和播散的恶性肿瘤。
