title: Antiarthritic and chondroprotective activity of Lakshadi Guggul in novel alginate-enclosed chitosan calcium phosphate nanocarriers.
abstract: OBJECTIVE
  This study aimed to evaluate the antiarthritic and chondroprotective potentials of Lakshadi Guggul (LG) and Cissus quadrangularis encapsulated in novel alginate-enclosed chitosan-calcium phosphate nanocarriers (NCs) both in vitro in primary human chondrocytes and in vivo in mice with collagen-induced arthritis.
  
  
  METHODS
  Chondrocytes exposed to IL-1β and osteoarthritis chondrocytes grown in an ex vivo inflammation-based coculture were incubated with different concentrations of herbals, and cell modulatory activities were determined. For in vivo studies, herbals and their encapsulated nanoformulations were administered orally to DBA/1 mice with collagen-induced arthritis.
  
  
  RESULTS
  C. quadrangularis and LG showed enhanced chondroprotective and proliferative activity in IL-1β-exposed primary chondrocytes, with LG showing the highest therapeutic potency. LG increased viability, proliferative and mitogenic activity, and inhibited cell apoptosis and mitochondrial depolarization. In vivo studies with LG and alginate-enclosed chitosan-calcium phosphate LG NCs revealed cartilage regenerative activity in those administered with the nanoformulation. The NCs were nontoxic to mice, reduced joint swelling and paw volume, and inhibited gene expression of MMPs and cytokines.
  
  
  CONCLUSIONS
  The promising results from this study reveal, for the first time, the novel polymeric NC encapsulating LG as a potential therapeutic for rheumatic diseases.
authors.affiliation: Nanomedicine-Laboratory of Immunology & Molecular Biomedical Research (NLIMBR), School of Medicine (SoM), Molecular & Medical Research (MMR) Strategic Research Centre, Faculty of Health, Technology Precinct (GTP), Deakin University, Waurn Ponds, Victoria 3217, Australia.
authors.forename: Rasika M
authors.initials: RM
authors.lastname: Samarasinghe
authors.forename: Rupinder K
authors.initials: RK
authors.lastname: Kanwar
authors.forename: Kuldeep
authors.initials: K
authors.lastname: Kumar
authors.forename: Jagat R
authors.initials: JR
authors.lastname: Kanwar
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002130:Calcium Phosphates / Q000737:chemistry*; D002460:Cell Line; D048271:Chitosan / Q000031:analogs & derivatives*; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D029744:Commiphora / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology; D008297:Male; D008811:Mice, Inbred DBA; D049329:Nanostructures / Q000737:chemistry; D010936:Plant Extracts / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D053149:Plant Gums / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000464:Alginates; D000893:Anti-Inflammatory Agents; D002130:Calcium Phosphates; D004337:Drug Carriers; D006603:Hexuronic Acids; D053583:Interleukin-1beta; D010936:Plant Extracts; D053149:Plant Gums; C018562:guggulu extract; D020723:Glucuronic Acid; D048271:Chitosan; C020243:calcium phosphate
keywords: Cissus quadrangularis; Lakshadi Guggul; alginate; anti-inflammatory; antiarthritic; chitosan; collagen-induced arthritis; nanocarrier; oral delivery; osteoarthritis