Abdelkader E Ashour1,2, Mohammad Badran3, Ashok Kumar4, Tajamul Hussain5, Ibrahim A Alsarra3, Alaa Eldeen B Yassin3,6,7. 1. Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. 2. Department of Basic Medical Sciences, Kulliyyah of Medicine, International Islamic University Malaysia, Kuantan 25200, Pahang Darul Makmur, Malaysia. 3. Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. 4. Vitiligo Research Chair, College of Medicine, King Saud University, Riyadh, Saudi Arabia. 5. Center of Excellence in Biotechnology Research, King Saud University, Riyadh, KSA. 6. Pharmaceutical Sciences Department, College of Pharmacy-3163, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. 7. King Abdullah International Medical Research Center, Ministry of National Guard, Health Affairs, Riyadh, Saudi Arabia.
Abstract
PURPOSE: The main goal of this study is to evaluate the impact of physical incorporation of polyethylene glycol (PEG) into 5-fluorouracil (5-FU)-loaded polymeric nanoparticles (NPs). METHODS: The 5-FU-loaded NPs were prepared utilizing a simple double emulsion method using polycaprolactone (PCL) and polylactic-co-glycolic acid (PLGA) with or without PEG 6000. The surface charge, particle size, and shape of NPs were evaluated by standard procedures. Both Fourier Transform Infrared Spectroscopy and X-ray diffraction spectra of the 5-FU loaded NPs were compared against the pure 5-FU. The in vitro release profile of 5-FU from the NPs was monitored by the dialysis tubing method. Cell death and apoptosis induction in response to 5-FU NP exposure were measured by MTT and Annexin-V/7-amino-actinomycin D (7-AAD) assays, respectively, in Daoy, HepG2, and HT-29 cancer cell lines. RESULTS: The 5-FU loaded NPs were found to be spherical in shape with size ranging between 176±6.7 and 253.9±8.6 nm. The zeta potential varied between -7.13± 0.13 and -27.06±3.18 mV, and the entrapment efficiency was between 31.96% and 74.09%. The in vitro release of the drug followed a two-phase mode characterized by rapid release in the first 8 hrs followed by a period of slow release up to 72 hrs with composition-based variable extents. Cells exposed to NPs demonstrated a significant cell death which correlated with the ratio of PEG in the formulations in Daoy and HepG2 cells but not in HT-29 cells. Formulations (F1-F3) significantly induced early apoptosis in HT-29 cell lines. CONCLUSION: The physical PEGylation significantly enhanced the entrapment and loading efficiencies of 5-FU into NPs formulated with PLGA and PCL. It also fostered the in vitro cytotoxicity of 5-FU-loaded NPs in both Daoy and HepG2 cells. Induction of early apoptosis was confirmed for some of the formulations.
PURPOSE: The main goal of this study is to evaluate the impact of physical incorporation of polyethylene glycol (PEG) into 5-fluorouracil (5-FU)-loaded polymeric nanoparticles (NPs). METHODS: The 5-FU-loaded NPs were prepared utilizing a simple double emulsion method using polycaprolactone (PCL) and polylactic-co-glycolic acid (PLGA) with or without PEG 6000. The surface charge, particle size, and shape of NPs were evaluated by standard procedures. Both Fourier Transform Infrared Spectroscopy and X-ray diffraction spectra of the 5-FU loaded NPs were compared against the pure 5-FU. The in vitro release profile of 5-FU from the NPs was monitored by the dialysis tubing method. Cell death and apoptosis induction in response to 5-FU NP exposure were measured by MTT and Annexin-V/7-amino-actinomycin D (7-AAD) assays, respectively, in Daoy, HepG2, and HT-29 cancer cell lines. RESULTS: The 5-FU loaded NPs were found to be spherical in shape with size ranging between 176±6.7 and 253.9±8.6 nm. The zeta potential varied between -7.13± 0.13 and -27.06±3.18 mV, and the entrapment efficiency was between 31.96% and 74.09%. The in vitro release of the drug followed a two-phase mode characterized by rapid release in the first 8 hrs followed by a period of slow release up to 72 hrs with composition-based variable extents. Cells exposed to NPs demonstrated a significant cell death which correlated with the ratio of PEG in the formulations in Daoy and HepG2 cells but not in HT-29 cells. Formulations (F1-F3) significantly induced early apoptosis in HT-29 cell lines. CONCLUSION: The physical PEGylation significantly enhanced the entrapment and loading efficiencies of 5-FU into NPs formulated with PLGA and PCL. It also fostered the in vitro cytotoxicity of 5-FU-loaded NPs in both Daoy and HepG2 cells. Induction of early apoptosis was confirmed for some of the formulations.
Authors: Raghavendra C Mundargi; S Srirangarajan; Sunil A Agnihotri; Sangamesh A Patil; S Ravindra; Swati B Setty; Tejraj M Aminabhavi Journal: J Control Release Date: 2007-01-24 Impact factor: 9.776
Authors: Abdelkader E Ashour; Mohammad M Badran; Ashok Kumar; Arun K Rishi; Alaa Eldeen Yassin Journal: IEEE Trans Nanobioscience Date: 2016-10 Impact factor: 2.935
Authors: M E Nita; H Nagawa; O Tominaga; N Tsuno; S Fujii; S Sasaki; C G Fu; T Takenoue; T Tsuruo; T Muto Journal: Br J Cancer Date: 1998-10 Impact factor: 7.640