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Gold

nanoparticles targeted treatment for rheumatoid arthritis

question

question

Does GNPs drug delivery system incorporating MTX and folic acid

(FA) have strong efficacies against Rheumatoid arthritis (RA)?

Why we can not use methotrxate and folic acid alone at long term and We need an alternative treatment ?

question

So, Is the use targeting of MTX to inflamed joints is essential to the prevention of potential toxicity and improving therapeutic effects ?

hypothesis

Use a GNPs drug delivery system incorporating MTX and folic acid (FA) given a strong efficacies against RA and prevent toxicity of methotrxate

hypothesis

Introduction

Introduction

Rheumatoid arthritis

and treatment

Rheumatoid arthritis

Rheumatoid arthritis (RA)

A common systemic autoimmune disease that is characterized by symmetric pain and swelling of hands, wrists, feet, and knees, which impairs physical functions and quality of life(1).

It is a disabling and painful condition that, if not adequately treated, can lead to an immense loss of body functioning and mobility (2).

(RA)

(Figure 1) Rheumatoid arthritis causes pain and swelling in the joints; if untreated, the inflammatory disease may damage cartilage and bone.

Treatment of Rheumatoid arthritis (RA)

Methotrxate

Typically, methotrxate (MTX) is the drug of choice for early RA treatment. It can effectively treat RA at low doses (15–25 mg/week) (3).

Adverse reactions of methotrxate:

1)bone marrow suppression

2)gastrointestinal discomfort

3)mucosal skin damage

4)neurotoxicity.

Therefore, regular monitoring during administration is required.

  • 80% of MTX is metabolized in the kidneys, leading to nephrotoxicity, severe neutropenia, sepsis, and finally, advanced renal failure (4).

Currently, targeting drugs to joints is a new trend in RA treatment.

gold nanoparticles

gold nanoparticles

Gold as a therapeutic agent

  • Gold has been used as a therapeutic agent to treat a wide variety of rheumatic diseases including psoriatic arthritis, juvenile arthritis, and discoid lupus erythematosus(5).

  • Although the use of gold has been largely superseded by newer drugs, gold nanoparticles are being used effectively in laboratory based clinical diagnostic methods while concurrently showing great promise in vivo either as a diagnostic imaging agent or a therapeutic agent(5).

Gold as a therapeutic agent

Targeting methotrxate

Targeting of MTX to inflamed joints is essential to the prevention of potential toxicity and improving therapeutic effects(6).

Gold nanoparticles (GNPs) are characterized by controllable particle sizes and good biocompatibilities, therefore, they are promising drug delivery systems(6).

To to do the targeting methotrxate, designed a novel nanoparticle drug carrier system (GNPs/MTX-Cys-FA) nanoconjugate exhibited a spherical appearance .

  • Cys is the most common amino acid with a sulfhydryl group. Therefore, Cys is usually used as a linker to perform the solid-phase organic synthesis of MTX and FA.

  • Add folic acid to do drug to be more selective

  • It is suitable particle sizes, good stabilities, and excellent drug-carrying capacities.

  • The nanoconjugates were approximately 103.6 nm in size and were stable at a pH of 7.4, which is suitable for selective passive accumulation in inflammatory joints through the EPR effect. (6)

Fig. 2. Particle size, zeta potential and morphological observation

(Figure. 2). Particle size, zeta potential and morphological observation. (A) Particle size of GNPs. (B) Particle size of GNPs/MTX-Cys-FA. (C) Zeta potential of GNPs and

GNPs/MTX-Cys-FA. (D) TEM images of GNPs. (E) TEM images of GNPs/MTX-Cys-FA. (F) SEM images of GNPs. (G) SEM images of GNPs/MTX-Cys-FA. Scale 100 nm.

conclusion

& discussion

conclusion

&

discussion

conclusion

conclusion

This presentation focuses on gold nanoparticles as important area as targeting treatment of rheumatoid arthritis .

  • compared to free MTX, in vivo pharmacokinetic behaviors of the nanoconjugate were enhanced.
  • Accumulation levels of GNPs/MTX-Cys-FA in inflamed joints were elevated while their therapeutic effects were enhanced.

Side effects of conventional drugs have been minimized by conjugation with

gold nanoparticles and they increase the quality life of patients

**GNPs/MTX-Cys-FA nanoconjugates provide effective approaches for RA targeted therapeutic strategies.

discussion

Nanomaterials have achieved good therapeutic effects in the treatment of rheumatoid arthritis, their potential therapeutic mechanisms are still unclear, and there are still certain limitations in application.

We need to further explore and research the biocompatibility of the nanometer carrier and metabolic pathways in the body. Precise control of drug release rate and retention time is the direction that we should strive for next.

At present, most researches are only for single-targeted therapy.

We can consider targeting multiple targets to treat arthritis, using multiple drugs to synergistically block multiple pathways in the pathogenesis of RA, alleviate the disease process, and improve the therapeutic effect.

Perhaps it can become a new direction for the treatment of RA in the future.

We believe that with the development of nanotechnology, advanced nanomaterials will definitely play a key role in the treatment of rheumatoid arthritis in the future.

discussion

references

references

(1)Tateiwa, D., Yoshikawa, H., Kaito, T., 2019. Cartilage and Bone Destruction in Arthritis: pathogenesis and Treatment Strategy: a Literature Review. Cells 8.

(2)Madav, Y., Barve, K., Prabhakar, B., 2020. Current trends in theranostics for rheumatoid arthritis. Eur. J. Pharm. Sci. 145, 105240.

(3)Friedman, B., Cronstein, B., 2019. Methotrexate mechanism in treatment of rheumatoid arthritis. Joint Bone Spine 86 (3), 301–307.

(4)Abbasi, M., Mousavi, M.J., Jamalzehi, S., Alimohammadi, R., Bezvan, M.H., Mohammadi, H., Aslani, S., 2019. Strategies toward rheumatoid arthritis therapy; the old and the new. J. Cell. Physiol. 234 (7), 10018–10031.

(5)A. S. Thakor, J. Jokerst, C. Zavaleta, T. F. Massoud, and S. S. Gambhir ,2011. Gold Nanoparticles: A Revival in Precious Metal Administration to Patients, 4029–4036.

(6)Xuena Li , Huanhui Wang , Xiaotong Zou, Hui Su, Cheng Li, 2021. Methotrexate-loaded folic acid of solid-phase synthesis conjugated gold nanoparticles targeted treatment for rheumatoid arthritis, 0928-0987.

thank you

THANK YOU

Dania Raed Ali Obeidat

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