title: Preparation and optimization of PIT solid lipid nanoparticles via statistical factorial design.
abstract: The objective of this study was the preparation, physico-chemical characterization and statistical optimization of cationic solid lipid nanoparticles (SLN) prepared by the PIT method as potential carrier for gene therapy, emphasizing the application of factorial design in such a kind of studies. The preliminary screening from a physico-chemical point of view on three cationic lipids (CTAB, DDAB and DOTAP), selected on the basis of their different chemical structure and increasing lipophilicity, allowed us to select SLN with DOTAP, due to its higher zeta potential and smaller particle size. Afterward, a 2(2) full factorial experimental design was developed in order to study the effects of two independent variables (amount of DOTAP and concentration of lipid matrix) and their interaction on mean particle size and zeta potential values. The factorial planning was validated by ANOVA analysis; the correspondence between the predicted values of size and zeta and those measured experimentally confirmed the validity of the design and the equation applied for its resolution. The factorial design showed a significant influence of the independent variables on the selected parameters; in particular, a higher effect of DOTAP was observed on zeta potential value. Different dilutions of the optimized SLN containing 7% w/w of cutina CP and 1% w/w of DOTAP, with size and zeta potential values respectively of 462.9 nm and 50.8 mV, were in vitro examined to evaluate the possible cytotoxicity on two models of cell cultures: human prostate cancer androgen-non-responsive DU-145 cells and primary cultures of rat astrocytes.
authors.affiliation: Department of Drug Sciences, Faculty of Pharmacy, University of Catania, Catania, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Carbone
authors.forename: B
authors.initials: B
authors.lastname: Tomasello
authors.forename: B
authors.initials: B
authors.lastname: Ruozi
authors.forename: M
authors.initials: M
authors.lastname: Renis
authors.forename: G
authors.initials: G
authors.lastname: Puglisi
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D002412:Cations / Q000737:chemistry / Q000633:toxicity; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000077286:Cetrimonium; D002593:Cetrimonium Compounds / Q000737:chemistry / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D008055:Lipids / Q000737:chemistry* / Q000633:toxicity; D015233:Models, Statistical; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity / Q000648:ultrastructure; D036103:Nanotechnology / Q000379:methods*; D010168:Palmitates / Q000737:chemistry / Q000633:toxicity; D010316:Particle Size; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000633:toxicity; D051381:Rats
chemical_list: D002412:Cations; D002593:Cetrimonium Compounds; D004337:Drug Carriers; D005229:Fatty Acids, Monounsaturated; D008055:Lipids; D010168:Palmitates; D000644:Quaternary Ammonium Compounds; C046112:didodecyldimethylammonium; C006957:cetyl palmitate; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane; D000077286:Cetrimonium