Zhang Bo, Song Yunmei, Wang Tianqi, Yang Shaomei, Zhang Jing, Liu Yongjun, Zhang Na, Garg Sanjay
Department of Pharmaceutics, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong Province, People's Republic of China.
Centre for Pharmaceutical Innovation and Development (CPID), School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia.
Int J Nanomedicine. 2017 Apr 7;12:2871-2886. doi: 10.2147/IJN.S129091. eCollection 2017.
Combinational nanomedicine is becoming a topic of much interest in cancer therapy, although its translation into the clinic remains extremely challenging. One of the main obstacles lies in the difficulty to efficiently co-deliver immiscible hydrophilic/hydrophobic drugs into tumor sites. The aim of this study was to develop co-loaded lipid emulsions (LEs) to co-deliver immiscible hydrophilic/hydrophobic drugs to improve cancer therapy and to explore the co-delivery abilities between co-loaded LEs and mixture formulation. Multiple oxaliplatin/irinotecan drug-phospholipid complexes (DPCs) were formulated. Co-loaded LEs were prepared using DPC technique to efficiently encapsulate both drugs. Co-loaded LEs exhibited uniform particle size distribution, desired stability and synchronous release profiles in both drugs. Co-loaded LEs demonstrated superior anti-tumor activity compared with the simple solution mixture and the mixture of single-loaded LEs. Furthermore, co-loaded nanocarriers could co-deliver both drugs into the same cells more efficiently and exhibited the optimized synergistic effect. These results indicate that co-loaded LEs could be a desired formulation for enhanced cancer therapy with potential application prospects. The comparison between co-loaded LEs and mixture formulation is significant for pharmaceutical designs aimed at co-delivery of multiple drugs.
组合纳米药物正成为癌症治疗中备受关注的一个话题，尽管将其转化为临床应用仍然极具挑战性。主要障碍之一在于难以将互不相溶的亲水性/疏水性药物有效地共同递送至肿瘤部位。本研究的目的是开发共载脂质乳剂（LEs），以共同递送互不相溶的亲水性/疏水性药物，从而改善癌症治疗，并探索共载LEs与混合制剂之间的共同递送能力。制备了多种奥沙利铂/伊立替康药物-磷脂复合物（DPCs）。采用DPC技术制备共载LEs，以有效包封两种药物。共载LEs表现出均匀的粒径分布、所需的稳定性以及两种药物的同步释放曲线。与简单溶液混合物和单载LEs的混合物相比，共载LEs表现出卓越的抗肿瘤活性。此外，共载纳米载体能够更有效地将两种药物共同递送至同一细胞，并展现出优化的协同效应。这些结果表明，共载LEs可能是一种用于增强癌症治疗的理想制剂，具有潜在的应用前景。共载LEs与混合制剂之间的比较对于旨在共同递送多种药物的药物设计具有重要意义。
