title: Preparation and evaluation of biopolymeric nanoparticles as drug delivery system in effective treatment of rheumatoid arthritis.
abstract: The study purposes to evaluate nanocrystalline biopolymeric nanoparticles encapsulating methotrexate and dexamethasone with high biocompatibility, enhanced therapeutic efficacy and reduced toxicity.
  
  
  
  Chitosan nanoparticles were prepared by ionic gelation, and Methotrexate (MTX) and Dexamethasone (DEX) were loaded during the preparation and screened for their in vitro efficacy in HEK and RAW264.7 cells, ex vivo and in vivo efficacy.
  
  
  
  FTIR confirmed the involvement of phosphoric group of sTPP with amine groups of chitosan and also role of hydrogen bonding involved in the preparation of MTXCHNP and DEXCHNP. Controlled release patterns coupled with diffusion of drug were observed in two different buffers (PBS) at pH 7.4 and pH 5.8. The IC50 for MTXCHNP for HEK was 26.1 μg/ml and 7.7 μg/ml for RAW 264.7 cells. In DEXCHNP, the IC50 was 20.12 μg/ml for HEK and 7.37 μg/ml for RAW264.7 cells. Enhanced uptake of FITC-CHNP by RAW cells indicated internalization of nanoparticles by phagocytosis. The enhanced release of drug at lower pH justified increased cytotoxicity. Negligible ex-vivo hemolysis indicated the higher biocompatibility of the nanoparticles.99mTc-CHNP exhibited maximum absorption in blood circulation in 3 h, followed by hepatic metabolism and renal clearance. Higher in-vivo anti-arthritic activity and antioxidant activity was observed post-intraperitoneal (i.p.) injections by both MTXCHNP and DEXCHNP when compared to MTX (0.75 mg/Kg by i.p. route) and DEX (0.2 mg/Kg/i.p./daily) per se.
  
  
  
  The nanocrystalline biopolymeric nanoparticles were stable, biocompatible and have potential to be administered through i.p. route with minimal toxicity and high efficacy.
authors.affiliation: Nano Biotech Lab, Department of Zoology, Kirori Mal College, University of Delhi, Delhi, 110007, India.
authors.forename: Vijay
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Nano Biotech Lab, Department of Zoology, Kirori Mal College, University of Delhi, Delhi, 110007, India.
authors.forename: Ankita
authors.initials: A
authors.lastname: Leekha
authors.affiliation: Nano Biotech Lab, Department of Zoology, Kirori Mal College, University of Delhi, Delhi, 110007, India.
authors.forename: Aakriti
authors.initials: A
authors.lastname: Tyagi
authors.affiliation: Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Delhi, 110054, India.
authors.forename: Ankur
authors.initials: A
authors.lastname: Kaul
authors.affiliation: Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Delhi, 110054, India.
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Mishra
authors.affiliation: Nano Biotech Lab, Department of Zoology, Kirori Mal College, University of Delhi, Delhi, 110007, India. akamra23@hotmail.com.
authors.forename: Anita Kamra
authors.initials: AK
authors.lastname: Verma
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001672:Biocompatible Materials; D018929:Cell Culture Techniques; D002460:Cell Line; D048271:Chitosan / Q000737:chemistry*; D003907:Dexamethasone / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008727:Methotrexate / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D017208:Rats, Wistar; D013499:Surface Properties; D014018:Tissue Distribution
chemical_list: D000975:Antioxidants; D018501:Antirheumatic Agents; D001672:Biocompatible Materials; D005079:Excipients; D003907:Dexamethasone; D048271:Chitosan; D008727:Methotrexate
keywords: antioxidants; arthritis; biodistribution; chitosan nanoparticles; inflammation