Nano Methotrexate versus Methotrexate in Targeting Rheumatoid Arthritis

Heba F Salem¹, Marwa Mohamed Abd El-Maboud², Amira S A Said^{2

3}, Mohamed Nabil Salem⁴, Dina Sabry^{5

6}, Nadia Hussain⁷, Omnia A M Abd El-Ghafar⁸, Raghda R S Hussein^{2

9}

Affiliations

¹ Department of Pharmaceutics & Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62521, Egypt.
² Department of Clinical Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62521, Egypt.
³ Department of Clinical Pharmacy, College of Pharmacy, Al Ain University, Al Ain P.O. Box 112612, United Arab Emirates.
⁴ Department of Internal Medicine, Faculty of Medicine, Beni-Suef University, Beni-Suef 62521, Egypt.
⁵ Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Badr University in Cairo, Cairo 11562, Egypt.
⁶ Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Giza 12613, Egypt.
⁷ Department of Pharmaceutical Sciences, College of Pharmacy, Al Ain University, Al Ain P.O. Box 112612, United Arab Emirates.
⁸ Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni Suef 62511, Egypt.
⁹ Department of Clinical Pharmacy, Faculty of Pharmacy, October 6 University, Giza 12585, Egypt.

PMID: 36678557
PMCID: PMC9866098
DOI: 10.3390/ph16010060

Nano Methotrexate versus Methotrexate in Targeting Rheumatoid Arthritis

Heba F Salem et al. Pharmaceuticals (Basel). 2022.

. 2022 Dec 31;16(1):60.

doi: 10.3390/ph16010060.

Authors

Heba F Salem¹, Marwa Mohamed Abd El-Maboud², Amira S A Said^{2

3}, Mohamed Nabil Salem⁴, Dina Sabry^{5

6}, Nadia Hussain⁷, Omnia A M Abd El-Ghafar⁸, Raghda R S Hussein^{2

9}

Affiliations

¹ Department of Pharmaceutics & Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62521, Egypt.
² Department of Clinical Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62521, Egypt.
³ Department of Clinical Pharmacy, College of Pharmacy, Al Ain University, Al Ain P.O. Box 112612, United Arab Emirates.
⁴ Department of Internal Medicine, Faculty of Medicine, Beni-Suef University, Beni-Suef 62521, Egypt.
⁵ Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Badr University in Cairo, Cairo 11562, Egypt.
⁶ Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Giza 12613, Egypt.
⁷ Department of Pharmaceutical Sciences, College of Pharmacy, Al Ain University, Al Ain P.O. Box 112612, United Arab Emirates.
⁸ Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni Suef 62511, Egypt.
⁹ Department of Clinical Pharmacy, Faculty of Pharmacy, October 6 University, Giza 12585, Egypt.

PMID: 36678557
PMCID: PMC9866098
DOI: 10.3390/ph16010060

Abstract

Nanomedicine has emerged as an important approach for targeting RA medication. Rheumatoid arthritis (RA) is a widespread autoimmune disorder marked by multiple inflamed joints. Gold nanoparticles (GNPs) have been demonstrated as efficacious nanocarriers due to their unique characteristics and the relative simplicity of their synthesis in varied sizes; moreover, they have the capability to alleviate several inflammatory markers. The current objective was to combine methotrexate (MTX) with GNPs to overcome MTX restrictions. GNPs were fabricated by a chemical reduction technique, utilizing sodium citrate and tween 20. The MTX-GNPs formulations were characterized in vitro by % entrapment efficiency (%EE), particle size, polydispersity index (PDI) zeta potential, and % release. The MTX-GNPs formulation was administrated as an intra-articular solution, and additionally, incorporated into a Carbopol gel to investigate its anti-arthritic effectiveness and bioavailability in vivo. The results indicated that a %EE of 87.53 ± 1.10%, and a particle size of 60.62 ± 2.41 nm with a PDI of 0.31 ± 0.03, and a zeta potential of −27.80 ± 0.36 mV were optimal. The in vitro release of MTX from the MTX-GNPs formulation demonstrated that the MTX-GNPs formulation’s release was 34.91 ± 1.96% and considerably (p < 0.05) lower than that of free MTX, showing a significant difference in dissolution patterns (p < 0.05). In vivo, MTX-GNPs formulations inhibited IL-6 by 36.52%, ACCP (63.25 %), COMP (28.16%), and RANKL (63.67%), as well as elevated IL-10 by 190.18%. Transdermal MTX-GNPs decreased IL-6 by 22.52%, ACCP (56.63%), COMP (52.64%), and RANKL (79.5%), as well as increased IL-10 by 168.37%. Histological investigation supported these recent findings. Conclusions: Marked improvements in MTX anti-arthritic effects are seen when it is conjugated to GNPs.

Keywords: bioavailability; effectiveness; gold nanoparticles; inflamed joints; intra-articular; nanomedicine; transdermal.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
In vitro release profile of MXT from free MXT and MLG formulations (n = 3 ± SD).

**Figure 2**
Comparative UV-Vis absorption spectra of free MTX, GNPs, and MTX-GNPs.

**Figure 3**
Surface morphology of MTX-GNPs by SEM.

**Figure 4**
(a) Effect of MTX, MTX-Nano solution, and MTX-Nano gel on Anti-CCP in CFA induced rheumatoid arthritis; (b) effect of MTX, MTX-Nano solution, and MTX-Nano gel on IL6 in CFA induced rheumatoid arthritis; (c) effect of MTX, MTX-Nano solution, and MTX-Nano gel on IL-10 in CFA induced rheumatoid arthritis; (d) effect of MTX, MTX-Nano solution, and MTX-Nano gel on RANKL in CFA induced rheumatoid arthritis; (e) effect of MTX, MTX-Nano solution, and MTX-Nano gel on COMP in CFA induced rheumatoid arthritis; (f) histopathologic examinations under a light microscope on knee joints by H&E staining (magnification ×200 and ×100).

See this image and copyright information in PMC

References

1. Sadarani B., Majumdar A., Paradkar S., Mathur A., Sachdev S., Mohanty B., Chaudhari P. Enhanced skin permeation of Methotrexate from penetration enhancer containing vesicles: In vitro optimization and in vivo evaluation. Biomed. Pharmacother. 2019;114:108770. doi: 10.1016/j.biopha.2019.108770. - DOI - PubMed
1. Ruaro B., Casabella A., Paolino S., Pizzorni C., Ghio M., Seriolo C., Molfetta L., Odetti P., Smith V., Cutolo M. Dickkopf-1 (Dkk-1) serum levels in systemic sclerosis and rheumatoid arthritis patients: Correlation with the Trabecular Bone Score (TBS) Clin. Rheumatol. 2018;37:3057–3062. doi: 10.1007/s10067-018-4322-9. - DOI - PubMed
1. Guajardo-Jauregui N., Galarza-Delgado D.Á., Azpiri-López J.R., Colunga-Pedraza I.J., Cárdenas A., Garza-Cisneros A.N., Garcia-Heredia A., Balderas-Palacios M.A., Rodriguez-Romero A.B. POS0577 Comparison of the Who and Acc/Aha Cardiovascular Algorithms to Detect Carotid Plaque in Rheumatoid Arthritis. BMJ Ann. Rheum. Dis. 2022;81:555. doi: 10.1136/annrheumdis-2022-eular.5054. - DOI
1. Joshi D.C., Naskar A., Datta K., Sarkar U., Otia M.K., Khatoon T. Rheumatoid Arthrities: Etiology Pathophysiology and Modern Treatments. Int. J. Res. Appl. Sci. Biotechnol. 2022;9:32–39. doi: 10.31033/ijrasb.9.3.7. - DOI
1. Akiyama M., Kaneko Y. Pathogenesis, clinical features, and treatment strategy for rheumatoid arthritis-associated interstitial lung disease. Autoimmun. Rev. 2022;21:103056. doi: 10.1016/j.autrev.2022.103056. - DOI - PubMed

LinkOut - more resources

Full Text Sources
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Nano Methotrexate versus Methotrexate in Targeting Rheumatoid Arthritis

Affiliations

Nano Methotrexate versus Methotrexate in Targeting Rheumatoid Arthritis

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

Full Text Sources

Miscellaneous