Integrating the drug, disulfiram into the vitamin E-TPGS-modified PEGylated nanostructured lipid carriers to synergize its repurposing for anti-cancer therapy of solid tumors
| Autor: | Parikshit Banerjee, Li Zong, Arpan Mahanty, Tiantian Li, Bo Wang, Tianjiao Geng |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Vitamin
Drug media_common.quotation_subject Pharmaceutical Science Antineoplastic Agents 02 engineering and technology Polyethylene glycol Pharmacology 030226 pharmacology & pharmacy Polyethylene Glycols Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo Cell Line Tumor Neoplasms Disulfiram medicine Animals Humans Vitamin E Cytotoxicity IC50 media_common Drug Carriers Mice Inbred BALB C Drug Repositioning Drug Synergism Blood Proteins 021001 nanoscience & nanotechnology Lipids Nanostructures Drug Liberation chemistry PEGylation Female 0210 nano-technology medicine.drug |
| Zdroj: | International Journal of Pharmaceutics. 557:374-389 |
| ISSN: | 0378-5173 |
| DOI: | 10.1016/j.ijpharm.2018.12.051 |
| Popis: | The 'repurposed drug,' disulfiram (DSF), is an inexpensive FDA-approved anti-alcoholism drug with multi-target anti-cancer effect. However, the use of DSF in clinical settings remains limited due to its high instability in blood. In the present study, we created nanostructured lipid carriers (NLC) encapsulated DSF modified with d-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E-TPGS). A spherical shape, superior drug encapsulation (80.7%), and decreased crystallinity of DSF were confirmed with results obtained from TEM, XRD, and DSC analysis. Addition of TPGS considerably improved the physicochemical stability profile of NLC-encapsulated DSF under the different conditions tested here. Furthermore, TPGS-DSF-NLCs outperformed unmodified DSF-NLCs and the free DSF solution by having significantly higher cytotoxicity, lower IC50 value (4T1: 263.2 nM and MCF-7: 279.9 nM), and an enhanced cellular uptake in MCF7 and 4T1 cell lines. In vivo anti-tumor analysis in 4T1 murine xenograft model mice revealed a significant (p-value 0.05) decrease in tumor volume and higher tumor growth inhibition rate (48.24%) with TPGS-DSF-NLC treatment as compared to both the free DSF solution (8.49%) and DSF-NLC formulations (29.2%). Histopathology analysis of tumor tissues further confirmed a noticeably higher anti-tumor activity of TPGS-DSF-NLC through augmented cell necrosis in solid tumors. Hence, the present study established that addition of TPGS can synergize the anti-cancer activity of NLC-encapsulated DSF formulations, and thus, offer a promising anti-cancer delivery system for DSF. |
| Databáze: | OpenAIRE |
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