Abstract
Purpose: Hydroxyurea (HU) is a well-known chemotherapy drug with several side effects which limit its clinical application. This study was conducted to improve its therapeutic efficiency against breast cancer using liposomes as FDA-approved drug carriers. Methods: PEGylated nanoliposomes-containing HU (NL-HU) were made via a thin-film hydration method, and assessed in terms of zeta potential, size, morphology, release, stability, cellular uptake, and cytotoxicity. The particle size and zeta potential of NL-HU were specified by zeta-sizer. The drug release from liposomes was assessed by dialysis diffusion method. Cellular uptake was evaluated by flow cytometry. The cytotoxicity was designated by methyl thiazolyl diphenyl-tetrazolium bromide (MTT) test. Results: The size and zeta value of NL-HU were gotten as 85 nm and -27 mV, respectively. NL-HU were spherical.NL-HU vesicles were detected to be stable for two months. The slow drug release and Weibull kinetic model were obtained. Liposomes considerably enhanced the uptake of HU into BT-474 human breast cancer cells. The cytotoxicity of NL-HU on BT-474 cells was found to be significantly more than that of free HU. Conclusion: The results confirmed these PEGylated nanoliposomes containing drug are potentially suitable against in vitro model of breast cancer.
Highlights
Breast cancer is one of the most prevalent diseases, with a high death rate among women.[1,2] Current methods for breast cancer therapy are chemotherapy, radiotherapy, and surgery, but all three types of treatment cause high toxicity for patients by killing healthy cells beside cancer cells and leading to severe side effects.[3]
Liposomes considerably enhanced the uptake of HU into BT-474 human breast cancer cells
The polydispersity index was equal to 0.12±0.030 for nanoliposomal HU; the mean zeta potential of the nanoliposomes-containing HU (NL-HU) was equal to -27 ± 0.51 mV (Figure 1)
Summary
Breast cancer is one of the most prevalent diseases, with a high death rate among women.[1,2] Current methods for breast cancer therapy are chemotherapy, radiotherapy, and surgery, but all three types of treatment cause high toxicity for patients by killing healthy cells beside cancer cells and leading to severe side effects.[3] only a little quantity of the drug reaches the target tumor, and most of the drug enters healthy tissues or is rapidly removed.[4] Among the chemotherapy agents, hydroxyurea (HU) is a well-known, low cost, effective, and safe drug that is extensively applied in the treatment of human cancers.[5,6] this drug has several defects, such as rapid clearance from circulation, low bioavailability, and side effects in patients.[7] Liposomes are widely used as carriers for delivering anticancer drugs, with multiple approved products for use by patients.[8,9,10,11,12] In recent years, some researchers have focused on the designing nanosize liposomes with a prolonged circulation time in the blood flow that is believed to increase drug delivery to the tumor. HU-loaded PEGylated nanoliposomes were prepared and, first, assessed on BT-474 breast cancer cell
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