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

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.

Green synthesis of methoxy-poly(ethylene glycol)-block-poly(l-lactide-co-glycolide) copolymer using zinc proline as a biocompatible initiator for irinotecan delivery to colon cancer in vivo

“…37 Zhang et al developed liposomes co-loaded with oxaliplatin and irinotecan for combinational chemotherapy against colorectal cancer. 38 Giarra et al have observed the spontaneous arrangement of a tumor-targeting hyaluronic acid shell on irinotecan loaded PLGA nanoparticles. This led to improved CD44-expressing breast carcinoma cells targeting and cytotoxicity.…”

PNA-Modified Liposomes Improve the Delivery Efficacy of CAPIRI for the Synergistic Treatment of Colorectal Cancer

“…By Western blotting, we found that the molecular weight of MUC1 in HT29 and SW620 cells was not consistent, which was consistent with other studies showing that the different degrees of extracellular glycosylation of MUC1 cause the molecular weight to range from 240 to 500 kDa ( Nath and Mukherjee, 2014 ; Apostolopoulos et al, 2015 ). Subsequently, cellular uptake experiments showed that the coloaded liposomes achieved same-time and same-place drug delivery, which was beneficial in improving the synergistic drug efficacy ( Zhang et al, 2017 ; Du et al, 2020 ). Meanwhile, the fluorescence signals of FITC/Rhb-PNA-Lips were significantly higher than those of the FITC/Rhb-Lip group due to the specific binding of PNA-modified liposomes to MUC1, which enhanced the cellular uptake of liposomes, and the in vivo targeting analyses were consistent with the results in vitro ( Tang et al, 2020 ).…”

Chimeric Stimuli-Responsive Liposomes as Nanocarriers for the Delivery of the Anti-Glioma Agent TRAM-34

“…The interactions between 1,2-dipalmitoyl-sn-glycero-3phosphocholine (DPPC), TRAM-34 and PDMAEMA-b-PLMA 1 and 2 in physiological (phosphate buffer saline, PBS) and acidic environment (citrate buffer) were studied by means of differential scanning calorimetry (DSC) analysis and the diagrams are presented in Figure 3 for heating and Figure S1 for cooling, whereas the calorimetric parameter values are listed collectively in Table S1. Since EPC is a phospholipid mixture and does not exhibit a distinct transition curve, we chose DPPC for this study, which has a T m around 41 • C [29].…”