Cited by 89Nanoparticles: synthesis and applicationsNanoparticle-Based Drug DeliveryPharmacology and Nanomedicine Research

The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index; 1 of the 27 sources its claims cite were checked for support.

Novel Green Biosynthesis of 5-Fluorouracil Chromium Nanoparticles Using Harpullia pendula Extract for Treatment of Colorectal Cancer

Open access
Saddik, Mohammed S., Elsayed, Mahmoud M. A., Abdelkader, Mohamed Salaheldin A., El-Mokhtar, Mohamed A., Abdel-Aleem, Jelan A., Abu-Dief, Ahmed M., Al-Hakkani, Mostafa F., Farghaly, Hatem S., Abou-Taleb, Heba A.·2021·Pharmaceutics

Abstract

Colorectal cancer (CRC) is the third highest major cause of morbidity and mortality worldwide. Hence, many strategies and approaches have been widely developed for cancer treatment. This work prepared and evaluated the antitumor activity of 5-Fluorouracil (5-Fu) loaded chromium nanoparticles (5-FuCrNPs). The green biosynthesis approach using Harpullia (H) pendula aqueous extract was used for CrNPs preparation, which was further loaded with 5-Fu. The prepared NPs were characterized for morphology using scanning and transmission electron microscopes (SEM and TEM). The results revealed the formation of uniform, mono-dispersive, and highly stable CrNPs with a mean size of 23 nm. Encapsulation of 5-Fu over CrNPs, with a higher drug loading efficiency, was successful with a mean size of 29 nm being produced. In addition, Fourier transform infrared (FTIR) and X-ray diffraction pattern (XRD) were also used for the investigation. The drug 5-Fu was adsorbed on the surface of biosynthesized CrNPs in order to overcome its clinical resistance and increase its activity against CRC cells. Box–Behnken Design (BBD) and response surface methodology (RSM) were used to characterize and optimize the formulation factors (5-Fu concentration, CrNP weight, and temperature). Furthermore, the antitumor activity of the prepared 5-FuCrNPs was tested against CRC cells (CACO-2). This in vitro antitumor study demonstrated that 5-Fu-loaded CrNPs markedly decreased the IC50 of 5-Fu and exerted more cytotoxicity at nearly all concentrations than 5-Fu alone. In conclusion, 5-FuCrNPs is a promising drug delivery system for the effective treatment of CRC.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

5-Fu-loaded chromium nanoparticles were green-synthesized using Harpullia pendula extract and characterized, with the optimized 5-FuCrNPs showing a mean size of 29 nm and greater cytotoxicity against CACO-2 colorectal cancer cells than 5-Fu alone. The formulation reduced the 5-Fu IC50 from 106 to 19.7 µg/mL and increased late apoptosis at 30 µg/mL.

Key findings

  • CrNPs had a mean size of 23 nm and 5-FuCrNPs 29 nm; particles were spherical, monodispersed, and smooth. XRD peaks at 2θ 25.39°, 53.21°, and 73.30° corresponded to crystalline CrNPs, with crystallite size ~25.5 nm by Scherrer’s formula and 27.45 nm with micro-strain 10.24 × 10−3 by Williamson-Hall analysis.
  • Loading efficiency ranged from 55.87 ± 2.03% to 92.11 ± 3.23%; it increased with higher 5-Fu concentration and CrNP weight, while temperature had a non-significant effect despite LE% decreasing as temperature increased. The optimum formula N10 used 0.75% 5-Fu, 500 mg CrNPs, and 20 ± 1 °C.
  • In vitro release after 1 h ranged from 14.88 ± 1.88% to 24.12 ± 1.77%, and after 3 h from 62.15 ± 1.96% to 92.73 ± 1.33%; release increased with 5-Fu concentration and decreased with CrNP weight, while temperature was non-significant.
  • 5-FuCrNPs decreased the IC50 of 5-Fu from 106 to 19.7 µg/mL. At 30 µg/mL, late apoptotic cells were 42.7% with 5-FuCrNPs versus 20% with 5-Fu and 11.7% with CrNPs alone.

Methods

  • CrNPs were biosynthesized by mixing H. pendula aqueous leaf extract with CrCl3·6H2O at 35 °C, stirring for 2 h, leaving in the dark for 24 h, then centrifuging, washing, and drying. 5-Fu loading was optimized with a Box–Behnken design of 15 formulae using three factors: 5-Fu concentration (0.25, 0.5, 0.75%), CrNP weight (250, 500, 750 mg), and temperature (20 ± 1, 25 ± 1, 30 ± 1 °C); 5-FuCrNPs were separated by 50 kDa ultrafiltration.
  • Characterization used SEM, TEM, XRD, and FTIR; loading efficiency was determined spectrophotometrically from unbound 5-Fu at 265 nm. In vitro release used a paddle apparatus at 50 rpm with pH 1.2 for 1 h followed by pH 7.4 for 2 h.
  • Antitumor activity was tested on the CACO-2 colorectal adenocarcinoma cell line using the MTT assay for viability and IC50, and annexin V/propidium iodide flow cytometry for apoptosis.

Limitations

  • The paper has no dedicated limitations section. It states that 5-Fu has clinical limitations including acquired resistance, a short half-life of 10–20 min, and harmful side effects on bone marrow and the gastrointestinal tract; it also notes that studies on CrNPs are still lacking.
  • Evident from the text: the antitumor evaluation is in vitro only, uses a single CACO-2 cell line, and reports no in vivo animal or clinical data, pharmacokinetics, biodistribution, or long-term toxicity.
  • Evident from the text: the fitted LE% models explain only 36.23% and 37.87% of variability for 5-Fu concentration and CrNP weight, respectively, and significance was assessed at p < 0.1 (90% confidence), with temperature effects non-significant.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3390/pharmaceutics13020226

Cites

66 of 66 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Figures

Figure 1 Schematic diagram showing the details of green biosynthesis preparation method, where, (CrNPs) is Chromium nanoparticles, (5-Fu) 5-Fluorouracil, and (5-FuCrNPs) 5-Fluorouracil chromium nanoparticles.
Figure 1 Schematic diagram showing the details of green biosynthesis preparation method, where, (CrNPs) is Chromium nanoparticles, (5-Fu) 5-Fluorouracil, and (5-FuCrNPs) 5-Fluorouracil chromium nanoparticles.CC BY · PubMed Central
Figure 2 (a). X-ray powder diffraction (XRD) patterns of the prepared CrNPs. (b). The Williamson-Hall (W-H) plots for CrNPs. The calculations of (βcorrect) were carried out according to Psd-Voigt distribution functions.
Figure 2 (a). X-ray powder diffraction (XRD) patterns of the prepared CrNPs. (b). The Williamson-Hall (W-H) plots for CrNPs. The calculations of (βcorrect) were carried out according to Psd-Voigt distribution functions.CC BY · PubMed Central
Figure 3 Scanning electron micrographs of the prepared (a) CrNPs, (b) 5-FuCrNPs N1 and (c) N10.
Figure 3 Scanning electron micrographs of the prepared (a) CrNPs, (b) 5-FuCrNPs N1 and (c) N10.CC BY · PubMed Central
Figure 4 Transmission electron microscope analysis of the prepared CrNPs with a diameter distribution histogram.
Figure 4 Transmission electron microscope analysis of the prepared CrNPs with a diameter distribution histogram.CC BY · PubMed Central
Figure 5 Transmission electron microscope analysis of the prepared 5-FuCrNPs with a diameter distribution histogram.
Figure 5 Transmission electron microscope analysis of the prepared 5-FuCrNPs with a diameter distribution histogram.CC BY · PubMed Central
Figure 6 Fourier transform infrared spectra of the prepared CrNPs, 5-FuCrNPs, H. pendula extract, and 5-Fu.
Figure 6 Fourier transform infrared spectra of the prepared CrNPs, 5-FuCrNPs, H. pendula extract, and 5-Fu.CC BY · PubMed Central
Figure 7 Surface plots effects of different formulation factors on LE%.
Figure 7 Surface plots effects of different formulation factors on LE%.CC BY · PubMed Central
Figure 8 Surface plots effects of different formulation factors on Release after one h.
Figure 8 Surface plots effects of different formulation factors on Release after one h.CC BY · PubMed Central
Figure 9 Surface plots effects of different formulation factors on release after 1 h.
Figure 9 Surface plots effects of different formulation factors on release after 1 h.CC BY · PubMed Central
Figure 10 Viability of the CACO cells treated with different concentrations of 5-Fu and 5-FuCrNPs determined by the MTT assay (a). Flow cytometry analysis showing the frequency of apoptotic cells treated with 5-Fu (b), CrNPs (c), and 5-FuCrNPs (d).
Figure 10 Viability of the CACO cells treated with different concentrations of 5-Fu and 5-FuCrNPs determined by the MTT assay (a). Flow cytometry analysis showing the frequency of apoptotic cells treated with 5-Fu (b), CrNPs (c), and 5-FuCrNPs (d).CC BY · PubMed Central

Verification

Claims the paper makes

35 Own result · 16 Own interpretation · 9 No full text of the sources · 9 No basis given · 6 Check pending · 1 Not checked yet · accuracy not yet measured

Verify all 8 references — free account

Show all 47 claims

  • It may state two separate claims as one. 23
  • Probably not a substantial claim. 6
  • The quote only partly states this claim. 1
29 of 29
  • The authors state this as an assumption.

    This is the first study to report the formulation of 5-Fu-loaded CrNPs for possible use in the treatment of colorectal cancer.

    “As far as we know, this is the first study that has reported on the formulation of 5-Fu-loaded CrNPs for possible use in the treatment of CRC.”
  • The paper relies on this without support.

    The CACO-2 cell line is a valid model for colorectal cancer treatment response.

    “In addition, the in vitro anti-tumor activity of 5-FuCrNPs against a colorectal cell line (CACO-2) was investigated.”
  • The paper relies on this without support.

    The green biosynthesis of CrNPs decreases Cr toxicity and enhances its clearance from the body by conjugation with bile salts.

    “In addition to increasing drug bioavailability at absorption sites in the intestine, the green biosynthesis of CrNPs decreases Cr toxicity and enhances its clearance from the body by conjugation with bile salts.”
  • The paper relies on this without support.

    An increase in CrNP surface area with increasing NP weight allows more drug to be adsorbed on the surface in a monolayer pattern.

    “These results are in accordance with the fact that an increase in CrNP surface area with increasing NP weight allows more drug to be adsorbed on the surface on the monolayer pattern.”
  • The paper relies on this without support.

    The prepared 5-FuCrNP system is still intact at pH 1.2.

    “These results may be due to the difficulty of desorption of 5-Fu from CrNPs in the acidic environment and the nature of the prepared 5-FuCrNP system, which is still intact at a pH of 1.2.”
5 of 5

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

6 of 6

Citations

Cites

Show all 66 references

Research works printed but not linked: 2

  1. Saddik, 2020, Preparation and Characterization of Niosomal Carrier System of Hydrophilic Drug (Methylene Blue) for Photodynamic Therapy, Lat. Americ J. Pharm., 39, 561
  2. Muthukumran, 2011, Anti-diabetic activity of Dodonaea viscosa (L) leaf extracts, Int. J. Pharm. Tech. Res., 3, 136

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Metadata

Authors
Saddik, M. S., Elsayed, M. M. A., Abdelkader, M. S. A., El-Mokhtar, M. A., Abdel-Aleem, J. A., Abu-Dief, A. M., Al-Hakkani, M. F., Farghaly, H. S., & Abou-Taleb, H. A.
Affiliations
  • Sohag University (EG)
  • Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71516, Egypt
  • Assiut University (EG)
  • Chemistry Department, College of Science, Taibah University, Madinah 42353, Saudi Arabia
  • New Valley University (EG)
  • Nahda University (EG)
  • Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Nahda University (NUB), Beni-Suef 62511, Egypt
Corresponding author
Elsayed, Mahmoud M. A.
Venue
Pharmaceutics
Publisher
MDPI AG
Published
2021-02-06
Volume
13
Issue
2
Pages
226
ISSN
1999-4923 (ISSN-L)
OpenAlex
W3127644344
Cited by
89
References
66
Citations by year
2026: 7 · 2025: 16 · 2024: 21 · 2023: 16 · 2022: 24 · 2021: 5
FWCI
4.70
Type
journal article
Language
en
Open access
Locations
  • Pharmaceutics (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Physical Sciences › Materials Science › Materials Chemistry › Nanoparticles: synthesis and applications
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Pharmacology and Nanomedicine Research
Keywords
5-fluorouracil, chromium nanoparticles, green synthesis, plant extracts, drug delivery systems, colorectal cancer, Caco-2 cells, anticancer activity, drug loading, nanoparticle drug loading, cytotoxicity, Box-Behnken design, response surface methodology

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