title: Development of Molecularly Imprinted Olanzapine Nano-particles: In Vitro Characterization and In Vivo Evaluation.
abstract: Molecularly imprinted nano-particles (MINPs) selective for olanzapine were prepared using methacrylic acid (MA) as monomer, ethylene glycol dimethacrylate (EGDMA) as a cross-linker, and 2,2-azobis (2-isobutyronitrile) (AIBN) as the initiator in 36 different ratios. The reaction runs with considerable fine powder formation were selected for further binding and selectivity studies. The MINP with the best selectivity (MINP-32) was chosen for further structural characterization by Fourier transform infrared spectroscopy (FT-IR), thermal gravimetric analysis (TGA), scanning electron microscopy (SEM), adsorption-desorption isotherm for specific surface area, volume and average pore diameter determination. All characterization methods confirmed the successful formation of MINP. The optimum conditions for maximum template loading on the MINP-32 were found by experimental design using response surface methodology (RSM) and choosing absorbent amount, pH, and time as the main factors. MINPs with maximum template loading also indicated significant selectivity between template and its analog (clozapine). The release profile demonstrated a maximum release of about 95% after 288 h for MINP-32 in comparison with about 94% after 120 h for non-MINP-32. The same slow release of drug from MINP-32 was also observed during animal study of the plasma level of template, 20-28 μg/ml versus 5-10 μg/ml. The MINP-32 of this study represents a desirable ability to keep the memory of the template with significant selectivity and good capability to control the release of template in vitro and in vivo and hence could be a promising drug delivery system.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Nersi
authors.initials: N
authors.lastname: Jafary Omid
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Hoda
authors.initials: H
authors.lastname: Morovati
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Amini
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ahmad-Reza
authors.initials: AR
authors.lastname: Dehpour
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Partoazar
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Morteza
authors.initials: M
authors.lastname: Rafiee-Tehrani
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. dorkoosh@tums.ac.ir.|Pharmaceutical Products Technology Units Incubator, No. 1462, Kargar Ave., Tehran, Iran, 1439804448. dorkoosh@tums.ac.ir.
authors.forename: Farid
authors.initials: F
authors.lastname: Dorkoosh
mesh_terms: D000327:Adsorption; D000818:Animals; D001569:Benzodiazepines / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D008297:Male; D008689:Methacrylates / Q000737:chemistry; D008855:Microscopy, Electron, Scanning / Q000379:methods; D054802:Molecular Imprinting / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism; D009570:Nitriles / Q000737:chemistry; D000077152:Olanzapine; D011108:Polymers / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods
chemical_list: D008689:Methacrylates; D009570:Nitriles; D011108:Polymers; D001569:Benzodiazepines; C008384:methacrylic acid; C004919:ethylene dimethacrylate; C004526:azobis(isobutyronitrile); D000077152:Olanzapine
keywords: experimental design; molecularly imprinted polymers; nano-particles; olanzapine; schizophrenia