Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Dec;28(12):1548-1557.
doi: 10.1016/j.jsps.2020.10.003. Epub 2020 Oct 22.

Targeted drug delivery of Methotrexate in situ gels for the treatment of Rheumatoid Arthritis

Madhugiri Prakash Venkatesh  1 , Tegginmat Pramod Kumar  1 , Deeksha Ramananda Pai  1
Affiliations

Targeted drug delivery of Methotrexate in situ gels for the treatment of Rheumatoid Arthritis

Madhugiri Prakash Venkatesh et al. Saudi Pharm J. 2020 Dec.

Abstract

Rheumatoid arthritis (RA) is considered a debilitating disease that increases the risk of significant morbidity and premature mortality. To circumvent drug-related toxicity and ineffectiveness of anti-inflammatory drugs, there is a significant need for an advanced delivery system that increases bioavailability. The feasibility of in situ gel of methotrexate sodium (MTS) as an effective management for Rheumatoid arthritis was investigated. It was formulated with pluronic F-127 (PLF-127) as primary polymer, hydroxypropyl methylcellulose K4M (HK4M), and polycarbophil (PCL) as a copolymer and characterized by various parameters. The efficacy evaluation by Freund's complete adjuvant (FCA) model, biocompatibility assessment by histopathological studies conducted. The optimized in situ gel (M4) was thermoresponsive, released 93.26 ± 2.39% MTS at 96 hours. In addition, distribution of MTS was even in the optimized sterile and syringeable in situ gel. In vivo studies on wistar rats demonstrated a substantial reduction in paw oedema during the 28-day study period and were biocompatible with the tissues at the injection site. The study was successful in formulating, optimizing MTS in situ gel for effective management of RA.

Keywords: Drug targeting; In situ gel; Methotrexate sodium; Rheumatoid arthritis.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
FT-IR spectrum (A- Methotrexate, B- Formulation M4, C- Formulation M7).
Fig. 2
Fig. 2
Formulation of Methotrexate in-situ gels.
Fig. 3
Fig. 3
DSC thermogram of Methotrexate.
Fig. 4
Fig. 4
Effect of polymer (HK4M and PCL) concentration on gelation time (Sec) and gelation temperature (°C).
Fig. 5
Fig. 5
Effect of polymers (HK4M and PCL) concentration on syringeability (Sec), in vitro drug release studies (cumulative % drug release).
Fig. 6
Fig. 6
Effect of polymers (HK4M and PCL) concentration on viscosity (cps) at two different temperature i.e. 8 °C & 37 °C.
Fig. 7
Fig. 7
Comparative in vitro release profile of MTS in situ gels (Formulation- M2, M3 & M4).
Fig. 8
Fig. 8
Comparative in vitro release profile of MTS in situ gels (Formulation- M5, M6 & M7).
Fig. 9
Fig. 9
The anti-inflammatory effect of MTS in situ gels as assessed by a reduction in paw volume in rats with adjuvant arthritis model. (One day after treatment).
Fig. 10
Fig. 10
Representative H and E (hematoxylin and eosin) stained histological slides of joint tissues from healthy rat knees after injection with (A) 100 µL of saline and (B) 100 µL of MTS in situ gels (magnification: 100×).
Supplementary figure 1
Supplementary figure 1
See this image and copyright information in PMC

References

    1. Abdel-Nasser A.M., Rasker J.J., Vaikenburg H.A. Epidemiological and clinical aspects relating to the variability of rheumatoid arthritis. Semin. Arthritis. Rheum. 1997;27:123–140. - PubMed
    1. Albert C., Brocq O., Gerard D., Roux C., Euller-Ziegler L. Septic knee arthritis after intra-articular hyaluronate injection. Joint. Bone. Spine. 2006;73:205–207. - PubMed
    1. Avina-Zubieta J.A., Choi H.K., Sadatsafavi M., Etminan M., Esdaile J.M., Lacaille D. Risk of cardiovascular mortality in patients with rheumatoid arthritis: A meta-analysis of observational studies. Arthritis. Rheum. 2008;59:1690–1697. - PubMed
    1. Bozdag S., Dillen K., Vandervoort J., Ludwig A. The effect of freeze-drying with different cryoprotectants and gamma-irradiation sterilization on the characteristics of ciprofloxacin HCl-loaded poly(D, L-lactide-glycolide) nanoparticles. J. Pharm. Pharmacol. 2005;57:699–707. - PubMed
    1. Butoescu N., Jordan O., Doelker E. Intra-articular drug delivery systems for the treatment of rheumatic diseases: A review of the factors influencing their performance. Eur. J. Pharm. Biopharm. 2009;73:205–218. - PubMed

LinkOut - more resources