Gold-thiol-beaded albumin nanoparticles for chemo-combined pulsatile plasmonic laser therapy of Rheumatoid arthritis in rat model

Anuradha Gadeval; Neelima Anup; Bhakti Pawar; Shubham Mule; Shivam Otavi; Rakesh Sahu; Rakesh Kumar Tekade

doi:10.1016/j.ijpharm.2024.124882

Gold-thiol-beaded albumin nanoparticles for chemo-combined pulsatile plasmonic laser therapy of Rheumatoid arthritis in rat model

Int J Pharm. 2024 Dec 25;667(Pt A):124882. doi: 10.1016/j.ijpharm.2024.124882. Epub 2024 Oct 28.

Authors

Anuradha Gadeval¹, Neelima Anup¹, Bhakti Pawar¹, Shubham Mule¹, Shivam Otavi¹, Rakesh Sahu¹, Rakesh Kumar Tekade²

Affiliations

¹ National Institute of Pharmaceutical Education and Research (NIPER) Ahmedabad, An Institute of National Importance, Government of India, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Palaj, Opp. Air Force Station, Gandhinagar 382355, Gujarat, India.
² National Institute of Pharmaceutical Education and Research (NIPER) Ahmedabad, An Institute of National Importance, Government of India, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Palaj, Opp. Air Force Station, Gandhinagar 382355, Gujarat, India. Electronic address: [email protected].

PMID: 39471886
DOI: 10.1016/j.ijpharm.2024.124882

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory immune disease that causes synovial membrane inflammation and destruction of articular cartilage. Traditionally, methotrexate is a first-line drug for RA treatment. However, its therapeutic benefits are insufficient. Pulsatile Plasmonic laser therapy (PPLT) has recently emerged as a localized and new-generation intervention for RA. This investigation reports the development of nanoGold-thiol-beaded albumin nanoparticles containing Leflunomide (GTBA-NP-L; 54 nm, PDI: 0.15 and entrapment efficiency: >90 %) for treating RA in an arthritic rat model. Upon irradiation of the plasmonic laser, the nanoGold component of GTBA-NP-L showed a local thermogenic effect (1.5 W/cm² for 5 mins: ∼45 °C). This local thermal effect enhances drug release (1.5-fold) while co-delivering heat and antiarthritic leflunomide at inflamed RA joints site. In vitro and in vivo studies demonstrated significant antiarthritic effects of GTBA-NP-L, accompanied by reduced inflammatory stress in lipopolysaccharide (LPS)-activated RAW 264.7 macrophage cells and antigen-induced arthritis (AIA) rat model. GTBA-NP-L treatment significantly reduced the cell viability (49.66 ± 2.46 %), apoptosis (83.36 ± 4.30 %), cell cycle arrest (38.28 ± 2.85 %), ROS and Nitrite stress levels (178.92 ± 19.79 %), and suppressed pro-inflammatory cytokines (TNF-α: 4.81, IL-6: 3.07 and IL-1β: 4.46-fold). In the arthritic rat, GTBA-NP-L treatment reduced inflammation, paw edema (1.89-fold), pain perception (45-48 %), and impacted hematological (Hb and RBCs: 12-15 %, WBCs: 30-32 %), serological (RF: 50-54 %, CRP: 40-47 %), and radiological parameters. Conclusively, the study demonstrates that the chemo-combined Pulsatile Plasmonic laser therapy showed superior efficacy as compared to individual treatments, suggesting GTBA-NP-L as a potential therapeutic candidate for rheumatoid arthritis.

Keywords: AIA rat model; Leflunomide; Plasmonic laser therapy; Pulsatile thermogenic effect; Rheumatoid arthritis; nanoGold.

MeSH terms

Albumins / administration & dosage
Albumins / chemistry
Animals
Antirheumatic Agents / administration & dosage
Antirheumatic Agents / chemistry
Antirheumatic Agents / pharmacokinetics
Antirheumatic Agents / pharmacology
Arthritis, Experimental* / drug therapy
Arthritis, Rheumatoid* / drug therapy
Disease Models, Animal
Drug Liberation
Gold* / administration & dosage
Gold* / chemistry
Laser Therapy / methods
Leflunomide* / administration & dosage
Male
Mice
Nanoparticles
RAW 264.7 Cells
Rats
Rats, Sprague-Dawley
Sulfhydryl Compounds* / administration & dosage
Sulfhydryl Compounds* / chemistry

Substances

Gold
Leflunomide
Sulfhydryl Compounds
Albumins
Antirheumatic Agents