Multivariate analysis for the optimization of polysaccharide-based nanoparticles prepared by self-assembly.
Polysaccharide-based nanoparticles are promising carriers for drug delivery applications. The particle size influences the biodistribution of the nanoparticles; hence size distributions and polydispersity index (PDI) are critical characteristics. However, the preparation of stable particles with a low PDI is a challenging task and is usually based on empirical trials. In this study, we report the use of multivariate evaluation to optimize the formulation factors for the preparation of alginate-zinc nanoparticles by ionotropic gelation. The PDI was selected as the response variable. Particle size, size distributions, zeta potential and pH of the samples were also recorded. Two full factorial (mixed-level) designs were analyzed by partial least squares regression (PLS). In the first design, the influence of the polysaccharide and the crosslinker concentrations were studied. The results revealed that size distributions with a low PDI were obtained by using a low polysaccharide concentrations (0.03-0.05%) and a zinc concentration of 0.03% (w/w). However, a high polysaccharide concentration can be advantageous for drug delivery systems. Therefore, in the second design, a high alginate concentration was used (0.09%) and a reduction in the PDI was obtained by simultaneously increasing the ionic strength of the solvent and the zinc concentration. The multivariate analysis also revealed the interaction between the factors in terms of their effects on the PDI; hence, compared to traditional univariate analyses, the multivariate analysis allowed us to obtain a more complete understanding of the effects of the factors scrutinized. In addition, the results are considered useful in order to avoid extensive empirical tests for future formulation studies.
SiteDel Group, School of Pharmacy, University of Oslo, P. O. Box 1068, Blindern, 0316 Oslo, Norway. Electronic address: sara.pistone@farmasi.uio.no.
Sara
S
Pistone
SiteDel Group, School of Pharmacy, University of Oslo, P. O. Box 1068, Blindern, 0316 Oslo, Norway. Electronic address: ina_790@hotmail.com.
Dafina
D
Qoragllu
SiteDel Group, School of Pharmacy, University of Oslo, P. O. Box 1068, Blindern, 0316 Oslo, Norway. Electronic address: gro.smistad@farmasi.uio.no.
Gro
G
Smistad
SiteDel Group, School of Pharmacy, University of Oslo, P. O. Box 1068, Blindern, 0316 Oslo, Norway. Electronic address: marianne.hiorth@farmasi.uio.no.
Marianne
M
Hiorth
D004337:Drug Carriers / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D015999:Multivariate Analysis; D053758:Nanoparticles / Q000737:chemistry*; D009994:Osmolar Concentration; D011134:Polysaccharides / Q000737:chemistry*
D004337:Drug Carriers; D011134:Polysaccharides
Ionic crosslinking; Monodisperse; Polydispersity index; Polysaccharide nanoparticle; Sodium alginate; Zinc chloride