Efficient co-delivery of immiscible hydrophilic/hydrophobic chemotherapeutics by lipid emulsions for improved treatment of cancer

Abstract

Bo Zhang,1 Yunmei Song,2 Tianqi Wang,1 Shaomei Yang,1 Jing Zhang,1 Yongjun Liu,1 Na Zhang,1 Sanjay Garg2 1Department of Pharmaceutics, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong Province, People’s Republic of China; 2Centre for Pharmaceutical Innovation and Development (CPID), School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia Abstract: 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. Keywords: cancer, combination therapy, co-delivery, lipid emulsions, drug–phospholipid complex

Keywords

• cancer
• combination therapy
• co-delivery
• lipid emulsions
• drug-phospholipid complex