Efficient size control of amphiphilic cyclodextrin nanoparticles through a statistical mixture design methodology.

PURPOSE the aim of the study was to investigate size control of amphiphilic beta-cyclodextrin nanoparticles obtained by solvent displacement technique. METHODS An experimental design methodology for mixture design was undertaken using D-optimal approach with the following technique variables: water fraction X1 (40-70% v/v), acetone fraction X2 (0-60% v/v) and ethanol fraction X3 (0-60% v/v). RESULTS The resulting quadratic model obtained after logarithmic transformation of data and partial least-square regression was statistically validated and experimentally checked. Also, the morphology of the colloidal nanoparticles from selected experiments was observed by cryo-transmission electron microscopy. CONCLUSIONS This experimental design approach allowed to produce interesting amphiphilic beta-cyclodextrin nanoparticles with a predicted mean size varying from 60 to 400 nm.

[1]  S. Shapiro,et al.  An Analysis of Variance Test for Normality (Complete Samples) , 1965 .

[2]  Duchêne,et al.  Cyclodextrins in targeting. Application to nanoparticles. , 1999, Advanced drug delivery reviews.

[3]  John A. Nelder,et al.  A Simplex Method for Function Minimization , 1965, Comput. J..

[4]  Dominique Duchêne,et al.  Characterization of amphiphilic β-cyclodextrin nanospheres , 1996 .

[5]  R. Lamartine,et al.  An efficient regio-specific synthetic route to multiply substituted acyl-sulphated β-cyclodextrins , 2001 .

[6]  J. Putaux,et al.  Influence of chemical structure of amphiphilic beta-cyclodextrins on their ability to form stable nanoparticles. , 2002, International journal of pharmaceutics.

[7]  S. Lesieur,et al.  Phase behavior of fully hydrated DMPC-amphiphilic cyclodextrin systems. , 2000, Chemistry and physics of lipids.

[8]  G. Annadurai,et al.  Use of Box-Behnken design of experiments for the adsorption of verofix red using biopolymer , 1998 .

[9]  J. Royston An Extension of Shapiro and Wilk's W Test for Normality to Large Samples , 1982 .

[10]  J. Rieger,et al.  Organic Nanoparticles in the Aqueous Phase-Theory, Experiment, and Use. , 2001, Angewandte Chemie.

[11]  V. Lamer,et al.  Theory, Production and Mechanism of Formation of Monodispersed Hydrosols , 1950 .

[12]  J. Putaux,et al.  Long-term shelf stability of amphiphilic β-cyclodextrin nanosphere suspensions monitored by dynamic light scattering and cryo-transmission electron microscopy , 2004, Journal of microencapsulation.

[13]  A. Blayo,et al.  Preparation of aqueous anionic poly-(urethane-urea) dispersions: Influence of the nature and proportion of the urethane groups on the dispersion and polymer properties , 2004 .

[14]  W. DuMouchel,et al.  A simple Bayesian modification of D-optimal designs to reduce dependence on an assumed model , 1994 .

[15]  G. Ponchel,et al.  Cyclodextrins and carrier systems. , 1999, Journal of controlled release : official journal of the Controlled Release Society.

[16]  D. Cox,et al.  An Analysis of Transformations , 1964 .

[17]  G. Höfle,et al.  4‐Dialkylaminopyridines as Highly Active Acylation Catalysts. [New synthetic method (25)] , 1978 .