School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People's Republic of China.
Int J Nanomedicine. 2019 May 7;14:3311-3330. doi: 10.2147/IJN.S200847. eCollection 2019.
Oral route of administration is preferred for treating breast cancer, especially when continued disease management with good tolerability is required; however, orally administered chemotherapeutics combined with near-infrared (NIR) dyes are hindered by the low bioavailability, insufficient for the desired therapeutic efficacy. In this study, we developed a hybrid self-microemulsifying drug delivery system for co-loading curcumin-phospholipid complex and NIR dye IR780 (CUR/IR780@SMEDDS), to achieve combined phototherapeutic and chemotherapeutic effects against lung metastasis of breast cancer. CUR/IR780@SMEDDS were characterized. The efficacy against breast cancer metastasis was evaluated by photothermal and photodynamic assessment, cytotoxicity, invasion, and migration in metastatic 4T1 breast cancer cells in vitro, and in vivo oral bioavailability study in rats and pharmacodynamics studies in tumor-bearing nude mice. CUR/IR780@SMEDDS improved oral bioavailability of curcumin and IR780 in rats compared with curcumin and IR780 suspensions. CUR/IR780@SMEDDS exhibited remarkable photothermal and photodynamic effects in vitro. In metastatic 4T1 breast cancer cells, CUR/IR780@SMEDDS combined with localized NIR laser irradiation induced significant cytotoxicity and inhibited invasion and migration of 4T1 cells, an outcome attributable to cumulative effects of IR780-induced hyperthermia and pharmacological effects of curcumin. In orthotopic 4T1 tumor-bearing nude mice, combination of oral administration of CUR/IR780@SMEDDS with local NIR laser irradiation inhibited tumor progression and suppressed lung metastasis.
口服给药途径是治疗乳腺癌的首选方法,特别是在需要持续管理疾病且具有良好耐受性时;然而,口服给予的化疗药物与近红外(NIR)染料结合受到生物利用度低的限制,不足以达到所需的治疗效果。在本研究中,我们开发了一种混合自微乳给药系统,用于共同装载姜黄素-磷脂复合物和 NIR 染料 IR780(CUR/IR780@SMEDDS),以实现联合光热和化学治疗对乳腺癌肺转移的作用。 CUR/IR780@SMEDDS 进行了表征。通过光热和光动力评估、细胞毒性、转移性 4T1 乳腺癌细胞的侵袭和迁移的体外评估以及大鼠口服生物利用度研究和荷瘤裸鼠的药效学研究来评估对乳腺癌转移的疗效。 CUR/IR780@SMEDDS 提高了姜黄素和 IR780 在大鼠中的口服生物利用度,优于姜黄素和 IR780 混悬液。 CUR/IR780@SMEDDS 在体外表现出显著的光热和光动力作用。在转移性 4T1 乳腺癌细胞中,CUR/IR780@SMEDDS 联合局部 NIR 激光照射诱导了显著的细胞毒性,并抑制了 4T1 细胞的侵袭和迁移,这归因于 IR780 诱导的热疗和姜黄素的药理作用的累积效应。在原位 4T1 荷瘤裸鼠中,口服给予 CUR/IR780@SMEDDS 联合局部 NIR 激光照射抑制了肿瘤进展并抑制了肺转移。
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