title: Methylprednisolone acetate-loaded hydroxyapatite nanoparticles as a potential drug delivery system for treatment of rheumatoid arthritis: In vitro and in vivo evaluations.
abstract: The objective of this study was to improve the therapeutic efficacy of methylprednisolone acetate (MPA) in the treatment of rheumatoid arthritis (RA) by incorporating the drug into the hydroxyapatite (HAp) nanoparticles. The nanoparticles were synthesized using a chemical precipitation technique and their size and morphology were evaluated by dynamic light scattering and scanning electron microscopy (SEM). The solid-state behavior of the nanoparticles was also characterized by operating X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). The Brunauer-Emmett-Teller and Barrett-Joyner-Halenda N2 adsorption/desorption analyses were also performed to determine the surface area, Vm (the volume of the N2 adsorbed on the one gram of the HAp when the monolayer is complete) and the pore size of the samples. Furthermore, the therapeutic efficacy of the prepared nanoformulation on the adjuvant induced arthritic rats was assessed. HAp mesoporous nanoparticles with a particle size of 70.45nm, pore size of 2.71nm and drug loading of 44.53% were obtained. The specific surface area of HAp as well as the Vm values were decreased after the drug loading process. The nanoformulation revealed the slower drug release profile compared to the pure drug. The MTT assay indicated that the MPA-loaded nanoparticles had a lower cytotoxic effect on NIH-3T3 and CAOV-4 cell lines compared to the pure drug. Interestingly, the in vivo study confirmed that the drug-loaded nanoparticles could considerably decrease the paw volume and normalize the hematological abnormalities in the arthritic rats.
authors.affiliation: Research Center for Pharmaceutical Nanotechnology and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Samira
authors.initials: S
authors.lastname: Jafari
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Nasrin
authors.initials: N
authors.lastname: Maleki-Dizaji
authors.affiliation: Research Center for Pharmaceutical Nanotechnology and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Jaleh
authors.initials: J
authors.lastname: Barar
authors.affiliation: Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Barzegar-Jalali
authors.affiliation: Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Rameshrad
authors.affiliation: Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: adibkia@tbzmed.ac.ir.
authors.forename: Khosro
authors.initials: K
authors.lastname: Adibkia
mesh_terms: D000327:Adsorption; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D065546:Drug Liberation; D017886:Durapatite / Q000737:chemistry*; D006801:Humans; D007596:Joints / Q000187:drug effects / Q000473:pathology; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000077555:Methylprednisolone Acetate; D051379:Mice; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D011142:Polyvinyl Alcohol / Q000737:chemistry; D017208:Rats, Wistar
chemical_list: D000893:Anti-Inflammatory Agents; D000077555:Methylprednisolone Acetate; D011142:Polyvinyl Alcohol; D017886:Durapatite; D008775:Methylprednisolone
keywords: Cytotoxicity; Histopathological evaluation; Hydroxyapatite; Methylprednisolone acetate; Nanoparticles; Rheumatoid arthritis