title: Fabrication and efficacy evaluation of chloroquine nanoparticles in CFA-induced arthritic rats using TNF-α ELISA.
abstract: Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, stimulates various immune cells especially macrophages, causing release of various proinflammatory cytokines such as TNF-α leading to persistent synovitis. Chloroquine, an anti-malarial drug inhibits the production of TNF-α, thus, halting the disease progression. The aim of the present study was fabrication, characterization and demonstration of kinetic and dynamic efficacy of chloroquine loaded solid lipid nanoparticles (CQ-SLNs) in arthritic rats and in lowering TNF-α levels. CQ-SLNs were prepared using melt homogenization method and subjected to lyophilization. The particle size, zeta potential, PDI and entrapment efficiency were found to be 113.6±0.15nm, -27.8±1.21mV, 0.125±0.03 and 93.45±0.43% respectively. Ex vivo endocytic uptake studies revealed engrossment of endocytic pathways in the uptake of SLN from intestine. Plasma drug profile upon pharmacokinetic evaluation demonstrated increased AUC, half-life and decreased elimination rate of the drug. Pharmacodynamic studies revealed reduction in the paw volume, bone erosion and cartilage destruction, the same was also reflected in histopathological studies. The TNF-α ELISA concluded that the TNF-α level was significantly reduced in the synovial fluid upon treatment with CQ-SLN, thus, leading to the conclusion that CQ-SLN could be used as a potential in reducing inflammatory TNF-α at the arthritic site and halting the disease progression.
authors.affiliation: Department of Pharmaceutics, AISSMS College of Pharmacy, Kennedy Road, Near RTO, Pune 411001, India. Electronic address: mrbhalekar@gmail.com.
authors.forename: Mangesh R
authors.initials: MR
authors.lastname: Bhalekar
authors.affiliation: Department of Pharmaceutics, AISSMS College of Pharmacy, Kennedy Road, Near RTO, Pune 411001, India.
authors.forename: Prashant G
authors.initials: PG
authors.lastname: Upadhaya
authors.affiliation: Department of Pharmaceutics, AISSMS College of Pharmacy, Kennedy Road, Near RTO, Pune 411001, India.
authors.forename: Ashwini R
authors.initials: AR
authors.lastname: Madgulkar
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001842:Bone and Bones / Q000473:pathology; D002358:Cartilage, Articular / Q000473:pathology; D002738:Chloroquine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D005528:Foot / Q000473:pathology; D007421:Intestine, Small / Q000378:metabolism; D007719:Knee Joint / Q000473:pathology; D008055:Lipids / Q000737:chemistry; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013582:Synovial Fluid / Q000276:immunology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D018501:Antirheumatic Agents; D008055:Lipids; D014409:Tumor Necrosis Factor-alpha; D002738:Chloroquine
keywords: Chloroquine; Rheumatoid arthritis; Solid lipid nanoparticles; TNF ELISA assay