Lactoferrin- and RGD-comodified, temozolomide and vincristine-coloaded nanostructured lipid carriers for gliomatosis cerebri combination therapy

Abstract

Jicai Zhang, Xiang Xiao, Jianming Zhu, Ziyun Gao, Xianliang Lai, Xingen Zhu, Guohua Mao Department of Neurosurgery, Second Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China Purpose: Glioblastoma multiforme (GBM) is the most common malignant brain tumor originating in the central nervous system in adults. Based on nanotechnology such as liposomes, polymeric nanoparticles, and lipid nanoparticles, recent research efforts have been aimed to target drugs to the brain. Methods: In this study, lactoferrin- and arginine–glycine–aspartic acid (RGD) dual-ligand-comodified, temozolomide and vincristine-coloaded nanostructured lipid carriers (L/R-T/V-NLCs) were introduced for GBM combination therapy. The physicochemical properties of L/R-T/V-NLCs such as particle size, zeta potential, and encapsulated efficiency are measured. The drug release profile, cellular uptake, cytotoxicity, tissue distribution, and antitumor activity of L/R-T/V-NLCs are further investigated in vitro and in vivo. Results: L/R-T/V-NLCs were stable with nanosize and high drug encapsulation efficiency. L/R-T/V-NLCs exhibited sustained-release behavior, high cellular uptake, high cytotoxicity and synergy effects, increased drug accumulation in the tumor tissue, and obvious tumor inhibition efficiency with low systemic toxicity. Conclusion: L/R-T/V-NLCs could be a promising drug delivery system for glioblastoma chemotherapy. Keywords: gliomatosis cerebri, combination therapy, nanostructured lipid carriers, lactoferrin, arginine–glycine–aspartic acid peptide, vincristine, temozolomide

Keywords

• Gliomatosis cerebri
• combination therapy
• nanostructured lipid carriers
• lactoferrin
• arginine-glycine-aspartic acid peptide
• vincristine
• temozolomide