Folate receptor-mediated targeted therapy for rheumatoid arthritis by methotrexate-phospholipid complex...

Area of Science:

• Immunology
• Nanotechnology
• Pharmacology

Background:

• Rheumatoid arthritis (RA) is a prevalent autoimmune and inflammatory condition.
• Activated macrophages in joints are key drivers of RA initiation and progression.
• Current RA treatments, like methotrexate (MTX), face challenges with poor response and systemic toxicity.

Purpose of the Study:

• To develop a targeted drug delivery system for RA treatment.
• To enhance the efficacy and reduce the toxicity of methotrexate (MTX).
• To target activated macrophages in arthritic joints using folate receptor (FR) mediated delivery.

Main Methods:

• Formulation of methotrexate-loaded, macrophage-targeted nano-emulsions (MTX@PC-FA NEs).
• Utilized folate receptor (FR) overexpression on activated macrophages and FR-folate (FA) affinity for targeting.
• In vivo studies using adjuvant-induced arthritis (AIA) mice with DID-labelled NEs for imaging and flow cytometry.
• Therapeutic efficacy and toxicity assessments.

Main Results:

• In vivo imaging and flow cytometry confirmed high targeting of NEs to inflamed joints and macrophages.
• MTX@PC-FA NEs demonstrated significant therapeutic efficacy in a mouse model of RA.
• The targeted delivery strategy successfully reduced systemic toxicity associated with MTX.

Conclusions:

• MTX@PC-FA NEs represent a promising strategy for RA treatment.
• Targeting FR-expressed activated macrophages can enhance therapeutic outcomes.
• This approach offers a potential solution to improve RA treatment by increasing in situ activity and decreasing systemic toxicity.