title: Chitosan nanoparticles for siRNA delivery: optimization of processing/formulation parameters.
abstract: Chitosan nanoparticles were prepared using ultrasonication methodology at specific amplitudes and times of sonication. Subsequently, small interfering RNA (siRNA) was added to the solution at predetermined values of nitrogen to phosphorous ratio (N/P), and stirring time. Employing response surfaces generated from a statistical model, the effect of sonication time and amplitude, stirring time, and N/P ratio was studied on the particle size, polydispersity, and loading efficiency of prepared siRNA/chitosan nanoparticles. It was found that to obtain the smallest size, amplitude and time of sonication as well as stirring time should be kept at ∼45%, 165 seconds, and 50 minutes, respectively. Minimum polydispersity values were also obtained at similar values of sonication time/amplitude and stirring time in addition to N/P values of ∼28. Also, the maximum proportion of siRNA loading was observed at approximate values of 300 seconds, 80% and 280 for sonication time, amplitude, and N/P ratio, respectively. The optimum conditions (i.e., to prepare a sample with minimum values of particle size and polydispersity index and maximum values of loading efficiency) were determined as 60.6, 30.0 (seconds), 28.0, and 12.5 (minutes) for amplitude, time of sonication, N/P, and stirring time, respectively. In this scrutiny, the predicted values of optimum formulation were 456 nm size, 89.6% loading efficiency, and 0.4 polydispersity index.
authors.affiliation: 1 Biotechnology Research Center, Tehran University of Medical Sciences , Tehran, Iran .
authors.forename: Elina
authors.initials: E
authors.lastname: Esmaeilzadeh Gharehdaghi
authors.forename: Amir
authors.initials: A
authors.lastname: Amani
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Khoshayand
authors.forename: Mehdi
authors.initials: M
authors.lastname: Banan
authors.forename: Elika
authors.initials: E
authors.lastname: Esmaeilzadeh Gharehdaghi
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Amini
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Faramarzi
mesh_terms: D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D055785:Gene Knockdown Techniques / Q000379:methods*; D057809:HEK293 Cells; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry; D013010:Sonication
chemical_list: D004337:Drug Carriers; D034741:RNA, Small Interfering; D048271:Chitosan