5-Fluorouracil-Loaded PLGA Nanoparticles: Formulation, Physicochemical Characterisation, and In Vitro Anti-Cancer Activity

by Selleckchem | Oct 03 2023

The major goal of this investigation was to prepare a drug delivery of polymeric nanoparticles (NPs) from 5-fluorouracil (FU) that could be delivered intravenously and improve the therapeutic index of the FU. In order to achieve this, interfacial deposition method was used to prepare FU entrapped poly-(lactic-co-glycolic acid) nanoparticles (FU-PLGA-NPs). The influence of various experimental settings on the effectiveness of FU integration into the NPs was assessed. Our findings show that the technique used to prepare the organic phase and the ratio of the organic phase to the aqueous phase had the greatest impact on the effectiveness of FU integration into NPs. The results show that the preparation process produced spherical, homogenous, negatively charged particles with a nanometric size of 200 nm that are acceptable for intravenous delivery. A quick initial release over 24 h and then slow and steady release of FU from the formed NPs, exhibiting a biphasic pattern. Through the human small cell lung cancer cell line (NCI-H69), the in vitro anti-cancer potential of the FU-PLGA-NPs was evaluated. It was then associated to the in vitro anti-cancer potential of the marketed formulation Fluracil®. Investigations were also conducted into Cremophor-EL (Cre-EL) potential activity on live cells. The viability of NCI-H69 cells was drastically reduced when they were exposed to 50 µg·mL-1 Fluracil®. Our findings show that the integration of FU in NPs significantly increases the drug cytotoxic effect in comparison to Fluracil®, with this potential effect being particularly important for extended incubation durations.

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The main objective of this study was to develop a drug delivery system using polymeric nanoparticles (NPs) to enhance the therapeutic efficacy of 5-fluorouracil (FU) when administered intravenously. The researchers employed the interfacial deposition method to fabricate FU-entrapped nanoparticles using poly-(lactic-co-glycolic acid) (PLGA). They investigated the influence of various experimental parameters on the efficient integration of FU into the nanoparticles.

The results revealed that the technique utilized for the organic phase preparation and the ratio of the organic phase to the aqueous phase had the most significant impact on the successful incorporation of FU into the nanoparticles. The nanoparticles generated through this process exhibited desirable characteristics, including a spherical shape, homogeneous distribution, negative surface charge, and a nanometric size of approximately 200 nm, making them suitable for intravenous administration.

In terms of drug release kinetics, the FU-PLGA-NPs exhibited an initial burst release over a 24-hour period, followed by a sustained and gradual release of FU, demonstrating a biphasic pattern. This controlled release profile is advantageous for maintaining therapeutic drug levels over an extended period.

To assess the anticancer potential of FU-PLGA-NPs, the researchers conducted in vitro experiments using the human small cell lung cancer cell line NCI-H69. They compared the cytotoxicity of the FU-PLGA-NPs with that of the commercially available formulation Fluracil®. Additionally, they investigated the potential cytotoxic effects of Cremophor-EL (Cre-EL) on live cells.

The results indicated that the viability of NCI-H69 cells was significantly reduced when exposed to a concentration of 50 µg·mL-1 of Fluracil®. Furthermore, the integration of FU into the nanoparticles substantially enhanced the cytotoxic effect of the drug compared to Fluracil®. This potentiated effect was particularly notable when the cells were incubated for longer durations.

Overall, this investigation successfully developed polymeric nanoparticles loaded with FU using the interfacial deposition method. The prepared nanoparticles exhibited desirable characteristics for intravenous delivery and demonstrated enhanced anticancer activity compared to the marketed formulation Fluracil®. These findings suggest the potential of FU-PLGA-NPs as a promising drug delivery system for improving the therapeutic index of 5-fluorouracil.