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Folate-Functionalized Lipid Nanoemulsion to Deliver Chemo-Radiotherapeutics Together for the Effective Treatment of Nasopharyngeal Carcinoma

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Abstract

Aim of the investigation was to develop folate-functionalized lipid nanoemulsion (LNE) comprising chemo-radiotherapeutics for targeted delivery to nasopharyngeal carcinoma (NPC). Soy lecithin nanoemulsion of doxorubicin (Dox) and yittrium-90 (90Y) was prepared by nanoprecipitation using ultrasonic homogenization technique followed by folic acid conjugation. Nanoemulsion (Dox-LNE) was characterized as positively charged (zeta potential), spherical shape (transmission electron microscopy) nano-droplets of uniform size distribution (polydispersity index). No significant variation in parameters such as particle size, zeta potential, and polydispersity index was observed when the stability of Dox-LNE was assessed during long-term storage at room temperature and at 8000 rpm, 121°C temperature, and 5000 time dilution in water. In vitro release of Dox from Dox-LNE was observed to be controlled for at least 48 h. Folate decoration over Dox-LNE surface (FD-Dox-LNE) and incorporation of 90Y in FD-Dox-LNE (FD-Dox + 90Y-LNE) changed droplet size up to 50 nm; however, surface charge of Dox-LNE did not change significantly. FD-Dox + 90Y-LNE inhibited growth of cancerous cell line like CNE1 (folate receptor rich) in vitro and alleviated tumor volume in NPC-induced nude mice significantly as compared to Dox + 90Y-LNE. Massive necrosis and hemorrhage of CNE1 cells were observed by FD-Dox + 90Y-LNE (89.9%); however, inhibition of growth of nasal epithelial cells (RPMI 2650; folate deficient) by FD-Dox + 90Y-LNE and Dox + 90Y-LNE was observed to be 21.5 and 43.65%, respectively. The investigation highlights the vast utility of folate-decorated lipid emulsion in delivering chemo-radiotherapeutics to the specific NPC site. FD-Dox + 90Y-LNE might offer a cost-effective, safe, efficacious, and clinically pertinent option to the available therapeutics.

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Acknowledgments

This work was supported by a grant from the Natural Science Foundation of Shandong Province (No. ZR2013HM107).

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Authors and Affiliations

  1. Department of Otolaryngology, Qilu Hospital of Shandong University, NO.107, Wenhua West Road, Jinan, 250012, Shandong Province, People’s Republic of China

    Ying Liu & Xin-Liang Pan

  2. Department of Otolaryngology, Qingdao district of Qilu Hospital, Shandong University, Qingdao, China

    Xue-Min Yu & Rui-Jie Sun

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  1. Ying Liu
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  2. Xue-Min Yu
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  4. Xin-Liang Pan
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Correspondence to Xin-Liang Pan.

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Liu, Y., Yu, XM., Sun, RJ. et al. Folate-Functionalized Lipid Nanoemulsion to Deliver Chemo-Radiotherapeutics Together for the Effective Treatment of Nasopharyngeal Carcinoma. AAPS PharmSciTech 18, 1374–1381 (2017). https://doi.org/10.1208/s12249-016-0595-y

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  • DOI: https://doi.org/10.1208/s12249-016-0595-y

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