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  • Title: Preparation and characterization of PLGA-PEG-PLGA polymeric nanoparticles for co-delivery of 5-Fluorouracil and Chrysin.
    Author: Khaledi S, Jafari S, Hamidi S, Molavi O, Davaran S.
    Journal: J Biomater Sci Polym Ed; 2020 Jun; 31(9):1107-1126. PubMed ID: 32249693.
    Abstract:
    Despite significant advances in cancer therapy, chemotherapeutic agents are still the main types of drugs used to treat cancer patients. 5-Fluorouracil (5-FU) is the first-line treatment in several types of human cancers, however, nonspecific function, low plasma half-life, and high doses toxicity are the important barrier to achieve efficient response in cancer patients. The use of polymeric nanoparticles (NPs) for tumor targeted delivery of 5-FU in combination with other potent anticancer agent is considered an important strategy to enhance the therapeutic efficacy of 5-FU. In this study, we proposed to use PLGA-PEG-PLGA NPs to co-encapsulate 5-FU and Chrysin, a natural compound known to enhance the therapeutic efficacy of chemotherapy. NPs were prepared by double emulsion method and characterized for size and drug encapsulation efficacy. The cell growth inhibitory effect of prepared NPs was assessed by MTT assay in HT29 human colon cancer cell line. The analysis of NPs by dynamic light scattering showed that the developed NPs have average size of 40 nm. The encapsulation efficiency of NPs was 81.3% and 97.5% for 5-FU and Chrysin, respectively. Furthermore, the NPs showed a remarkable uptake in HT29 cells. NPs loaded with both 5-FU and Chrysin (5-FU@Chrysin loaded NPs) were found to have significantly higher growth inhibitory effects compared with NPs loaded with each drug alone in HT29 cell line. The synergistic anticancer effects of 5-FU and Chrysin loaded in NPs were confirmed with the combination index (CI) being 0.35. CI for combination therapy with free 5-FU and Chrysin was found to be 0.73, indicating weaker synergistic anticancer effects of these two drugs in free forms as compared with 5-FU@Chrysin loaded NPs. These finding indicates that co-delivery of 5-FU and Chrysin with PLGA-PEG-PLGA copolymer can be used to improve the therapeutic and functional delivery efficacy of 5-FU and Chrysin in cancer.
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