title: The effect of oral administration of iron saturated-bovine lactoferrin encapsulated chitosan-nanocarriers on osteoarthritis.
abstract: Osteoarthritis (OA) treatments have major limitations which include systemic toxicity, reduced joint retention and inability to inhibit disease progression. In this study, the therapeutic potentials of 100% iron saturated-bovine lactoferrin encapsulated in alginate-chitosan polymeric nanocarriers (AEC-CP-Fe-bLf-NCs) were examined in in vitro inflammatory OA model and in collagen-induced arthritis (CIA) mice. By diminishing IL-1β induced apoptotic and oxidative stress, chondrocyte protection and proliferation was up-regulated with C-CP-Fe-bLf-NCs as compared to void and C-CP-Apo(metal free)-bLf-NCs. Oral administration of nanocarriers in mice was non-toxic and it significantly induced disease modifying activity by reducing joint inflammation and significantly downregulating the expression of catabolic genes, IL-1β, NO, JNK and MAPK. In addition, up-regulation of type II collagen, aggrecan and inflammation depleted iron and calcium metabolisms via inhibition of miRNA of iron transporting receptors was shown in AEC-CP-Fe-bLf-NCs treated mice. In addition, AEC-CP-Fe-bLf-NCs dissoluted calcium pyrophosphate crystals found in mice joints indicating the significantly important therapeutic ability of nanoformulated Fe-bLf to be utilized in the treatment of chronic inflammatory rheumatic diseases such as OA.
authors.affiliation: Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), School of Medicine (SoM), Molecular and Medical Research (MMR) Strategic Research Centre, Faculty of Health, Technology Precinct (GTP), Deakin University, Waurn Ponds, Victoria 3216, Australia.
authors.forename: Rasika M
authors.initials: RM
authors.lastname: Samarasinghe
authors.affiliation: Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), School of Medicine (SoM), Molecular and Medical Research (MMR) Strategic Research Centre, Faculty of Health, Technology Precinct (GTP), Deakin University, Waurn Ponds, Victoria 3216, Australia.
authors.forename: Rupinder K
authors.initials: RK
authors.lastname: Kanwar
authors.affiliation: Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), School of Medicine (SoM), Molecular and Medical Research (MMR) Strategic Research Centre, Faculty of Health, Technology Precinct (GTP), Deakin University, Waurn Ponds, Victoria 3216, Australia. Electronic address: jagat.kanwar@deakin.edu.au.
authors.forename: Jagat R
authors.initials: JR
authors.lastname: Kanwar
mesh_terms: D000284:Administration, Oral; D000464:Alginates / Q000737:chemistry; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002417:Cattle; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D005786:Gene Expression Regulation / Q000187:drug effects; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D053583:Interleukin-1beta / Q000276:immunology; D007501:Iron / Q000008:administration & dosage* / Q000627:therapeutic use; D007596:Joints / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007781:Lactoferrin / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D049329:Nanostructures / Q000737:chemistry; D010003:Osteoarthritis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D000464:Alginates; D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D006603:Hexuronic Acids; D053583:Interleukin-1beta; D035683:MicroRNAs; D020723:Glucuronic Acid; D048271:Chitosan; D007501:Iron; D007781:Lactoferrin
keywords: Chitosan; Iron metabolism; Lactoferrin; Nanocarriers; Osteoarthritis; miRNA