Application of smart solid lipid nanoparticles to enhance the efficacy of 5-fluorouracil in the treatment of colorectal cancer

Abstract

5-Fluorouracil (5-FU) is a standard treatment option for colorectal cancer (CRC) but its rapid metabolism and systemic instability (short half-life) has hindered its therapeutic efficacy. The objective of this study was to develop a novel drug delivery system, solid lipid nanoparticle (SLN), capable of delivering high payload of 5-FU to treat CRC. The rational was to improve 5FU-nanocarrier compatibility and therapeutic efficacy. The SLN-loaded 5-FU was developed by utilizing a Strategic and unique Method to Advance and Refine the Treatment (SMART) of CRC through hot and cold homogenization approach. The SLN was made of unique PEGylated lipids and combination of the surfactants. Cytotoxicity studies, clonogenic assay, flow cytometry and confocal imaging were conducted to evaluate the effectiveness and cellular uptake of 5FU-SLN4 in HCT-116 cancer cells. Pharmacokinetic (PK) parameters and receptor expressions were determined while tumor efficacy studies were conducted on mouse bearing subcutaneous HCT-116 cancer. Among the all the formulations, 5FU-SLN4 was the most effective with particle size of was 263 ± 3 nm, zeta potential was 0.1 ± 0.02 and entrapment efficiency of 81 ± 10%. The IC50 value of 5FU-SLN4 (7.4 ± 0.02 µM) was 2.3 fold low compared with 5-FU (17.7 ± 0.03 µM). For tumor efficacy studies, 5FU-SLN4 significantly inhibited tumor growth in comparison to 5-FU while area-under plasma concentration-time curve (AUC) of 5FU-SLN4 was 3.6 fold high compared with 5-FU. HER2 receptors expression were markedly reduced in 5-FU-SLN4 treated mice compared with 5FU and liver and kidney tissues showed no toxicity at dose of 20 mg/kg. 5FU-SLN4 was highly cytotoxic against HCT-116 cells and significantly inhibited subcutaneous tumor growth in mice compared with 5-FU. This emphasizes the significance of developing a smart nano-delivery system to optimize the delivery efficiency of anticancer drugs to tumors.

CS/Au/MWCNT nanohybrid as an efficient carrier for the sustained release of 5-FU and a study of its cytotoxicity on MCF-7

“…Similarly, the zeta potential is seen to further decrease on the addition of 5-FU, having a negative zeta potential. 42 The zeta potential of all the prepared systems still remains high indicating the high stability of the prepared nanocomposites. The results clearly show the presence of two absorption peaks one in the wavelength range 540-545 nm and the other at $265 nm.…”

Current Landscape in Organic Nanosized Materials Advances for Improved Management of Colorectal Cancer Patients

“…The selected 5-FU PEGylated solid lipid nanoparticles show promising in vitro effects on HCT-116 cells and prolong plasma circulation of 5-FU. This 5-FU nanosystem triggered tumor growth suppression in tumor-bearing mice, with superior efficiency, compared to free 5-FU, by modulation of HER-2 expression, and further protected liver and kidney from 5-FU damage [163].…”

Antifungal Nano-Therapy in Veterinary Medicine: Current Status and Future Prospects

“…Polymeric nanoparticles such as solid lipid nanoparticles and dendrimers are also potent smart nanovehicles ensuring the targeted delivery of drug molecules in cancer tissues. Nanoencapsulation of 5-fluorouracil in solid lipid nanoparticles improved the specific problems associated with rapid metabolism and shorter life time [118]. This nanovehicle therefore improved the use of the 5-fluorouracil for treatment of colorectal cancer conditions.…”