title: Preparation and optimization of surface-treated methotrexate-loaded nanogels intended for brain delivery.
abstract: Nanogels loaded with methotrexate (MTX) were prepared via an ionic gelation process using chitosan and sodium tripolyphosphate (TPP). The preparation process was optimized by a systematic multi-objective-optimization approach in terms of the size, poly-dispersity index (PDI), loading efficiency (LE) and loading capacity (LC) of the resulting nanocarriers. A combination of the pH of the chitosan solution, the addition time of the TPP solution and temperature effects accounted for nearly 75% of the variation in nanogel size; the TPP initial concentration had a very significant effect on LE (p<0.0001). The final particle size (Z-average (r nm)), PDI, LE and LC corresponding to the optimal conditions were 59.27 nm, 0.34, 61.82% and 53.68%, respectively. As the ultimate goal, the surfaces of the MTX-loaded nanogels were modified by polysorbate 80 for the purpose of brain targeting. The cumulative in vitro release profiles of surfactant-coated and uncoated nanogels were almost identical and showed acceptable performance.
authors.affiliation: Biopharmaceutics and Pharmacokinetic Division, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Azadi
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Zanjan University of Medical Sciences, P.O. Box 45139-56184, Zanjan, Iran.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Hamidi
authors.affiliation: Department of Drug and Food Control, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran.
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Khoshayand
authors.affiliation: Department of Medicinal Chemistry and Drug Design and Development Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Amini
authors.affiliation: Biopharmaceutics and Pharmacokinetic Division, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran.
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Rouini
mesh_terms: D001921:Brain / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D008727:Methotrexate / Q000008:administration & dosage / Q000138:chemical synthesis*; D000080385:Nanogels; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000138:chemical synthesis*; D011094:Polyethyleneimine / Q000008:administration & dosage / Q000138:chemical synthesis*; D013499:Surface Properties
chemical_list: D000080385:Nanogels; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D008727:Methotrexate