Improved Efficacy and Reduced Toxicity of Doxorubicin Encapsulated in Sulfatide-Containing Nanoliposome in a Glioma Model

Abstract

As a glycosphingolipid that can bind to several extracellular matrix proteins, sulfatide has the potential to become an effective targeting agent for tumors overexpressing tenasin-C in their microenvironment. To overcome the dose-limiting toxicity of doxorubicin (DOX), a sulfatide-containing nanoliposome (SCN) encapsulation approach was employed to improve treatment efficacy and reduce side effects of free DOX. This study analysed in vitro characteristics of sulfatide-containing nanoliposomal DOX (SCN-DOX) and assessed its cytotoxicity in vitro, as well as biodistribution, therapeutic efficacy, and systemic toxicity in a human glioblastoma U-118MG xenograft model. SCN-DOX was shown to achieve highest drug to lipid ratio (0.5∶1) and a remarkable in vitro stability. Moreover, DOX encapsulated in SCN was shown to be delivered into the nuclei and displayed prolonged retention over free DOX in U-118MG cells. This simple two-lipid SCN-DOX nanodrug has favourable pharmacokinetic attributes in terms of prolonged circulation time, reduced volume of distribution and enhanced bioavailability in healthy rats. As a result of the improved biodistribution, an enhanced treatment efficacy of SCN-DOX was found in glioma-bearing mice compared to the free drug. Finally, a reduction in the accumulation of DOX in the drug's principal toxicity organs achieved by SCN-DOX led to the diminished systemic toxicity as evident from the plasma biochemical analyses. Thus, SCN has the potential to be an effective and safer nano-carrier for targeted delivery of therapeutic agents to tumors with elevated expression of tenascin-C in their microenvironment.

Development of antiproliferative long-circulating liposomes co-encapsulating doxorubicin and curcumin, through the use of a quality-by-design approach

“…Moreover, this effect was visible at concentrations approximately two- to threefold lower than that of the free drug. This is in agreement with previous studies that demonstrated a remarkable enhancement of the cytotoxic actions of DOX when included in liposomes, nanoparticles or other lipid-based formulations 66–70. To enhance the efficacy of DOX for further in vivo studies, we designed two liposomal formulations based on the co-encapsulation of DOX and CUR.…”

“…This is in agreement with previous studies that demonstrated a remarkable enhancement of the cytotoxic actions of DOX when included in liposomes, nanoparticles or other lipid-based formulations. 66 – 70 To enhance the efficacy of DOX for further in vivo studies, we designed two liposomal formulations based on the co-encapsulation of DOX and CUR. The composition of these formulations was established using the Optimizer function in Modde 11 Pro software.…”

Transferrin and octaarginine modified dual-functional liposomes with improved cancer cell targeting and enhanced intracellular delivery for the treatment of ovarian cancer

“…The tumor growth inhibition study was initiated at an early stage of tumor growth, to test the therapeutic potential of the liposomes. With the help of literature survey a 2 mg/kg DOX dose was chosen (Gao et al., 2005 ; Biswas et al., 2013 ; Zhao et al., 2013 ; Apte et al., 2014 ; Lin et al., 2014 ; Sriraman et al., 2016 ; Zahmatkeshan et al., 2016 ). Compared to the control and free DOX-treated tumors, all the liposomal DOX groups showed effective control of tumor growth in vivo .…”

Multi-stimuli responsive Cu2S nanocrystals as trimodal imaging and synergistic chemo-photothermal therapy agents

“…Moreover the drug-facilitated toxicity is dependent on the release rate of DOX from the NCs at cellular level. 43 Though the IC 50 value of PEG-Cu 2 S-Fol-DOX is higher than that of free DOX, the favored targeting of cancer cells achieved by PEG-Cu 2 S-Fol-DOX is extremely beneficial for a drug delivery system. The PEG-Cu 2 S-Fol-DOX were found to preferentially accumulate in glioma cells (Figure.…”