Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Co-delivery of combretastatin A4 and docetaxel with pegylated nanostructured lipid carriers in tumor cells

Caifeng Jia¹, Sen Zhang¹, Wenpan Li¹, Chun Chu², Haiyang Hu², Mingxia Wang¹ , Dawei Chen²

¹Department of Clinical Pharmacology, The Fourth Hospital of Hebei Medical University and Hebei Provincial Tumor Hospital, 12 Jiankang Road, Shijiazhuang 050011, China; ²School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110000, China.

For correspondence:- Mingxia Wang Email: chendawei@syphu.edu.cn

Accepted: 7 October 2023 Published: 30 October 2023

Citation: Jia C, Zhang S, Li W, Chu C, Hu H, Wang M, et al. Co-delivery of combretastatin A4 and docetaxel with pegylated nanostructured lipid carriers in tumor cells. Trop J Pharm Res 2023; 22(10):2029-2037 doi: 10.4314/tjpr.v22i10.2

© 2023 The authors.
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Abstract

Purpose: To investigate a novel co-delivery system using nanostructured lipid carriers (NLCs) for simultaneous administration of two potent anti-cancer drugs, combretastatin A-4 (CA-4) and docetaxel (DTX), against tumor cells and vasculature.

Methods: The CA-4 and DTX co-loaded NLCs (C-D-NLC) were formulated and investigated for physical properties, stability, and drug release. Safety and efficacy of C-D-NLC were investigated on Lewis Lung Carcinoma (LLC) tumor cells in vitro and in vivo using cytotoxicity and anti-tumor assays. The pharmacokinetics of CA-4 and DTX in rats after intravenous injection of C-D-NLC were also studied to evaluate potential drug interactions.

Results: The C-D-NLC was successfully prepared with a spherical shape, mean size of 130 nm, negative charge, high encapsulation efficiency and drug loading of 94.89, 88.16, 2.44, and 4.52 for DTX and CA-4, respectively. Also, C-D-NLC had a significant inhibitory effect on LLC cells, superior to a single drug or solution group. Combretastatin A4 did not affect the pharmacokinetics of DTX, but combretastatin–docetaxel nanostructured lipid carriers (C-D-NLC) reduced plasma clearance of CA-4 and DTX, prolonged half-life, mean residence time, and increased area under concentration curves (AUC) values. Furthermore, combretastatin–docetaxel nanostructured lipid carriers (C-D-NLC) inhibited the growth of LLC tumors in mice and reduced drug toxicity.

Conclusion: Combretastatin–docetaxel nanostructured lipid carriers (C-D-NLC) sustain drug release and enhance tumor growth inhibition of CA-4 and DTX by targeting both tumor cells and vasculature. The co-delivery system prolongs drug circulation compared to solution administration. Thus, nanostructured lipid carriers (NLCs) with dual drug loading may be a promising strategy for clinical combination chemotherapy in future.

Keywords: Combination therapy, Angiogenesis, Nanostructured lipid carrier, Combretastatin A-4, Docetaxel