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  • Title: Optimization of linalool-loaded solid lipid nanoparticles using experimental factorial design and long-term stability studies with a new centrifugal sedimentation method.
    Author: Pereira I, Zielińska A, Ferreira NR, Silva AM, Souto EB.
    Journal: Int J Pharm; 2018 Oct 05; 549(1-2):261-270. PubMed ID: 30075252.
    Abstract:
    Linalool (C10H18O), also known as 3, 7-dimethyl-1, 6-octadien-3-ol, is the most common acyclic monoterpene tertiary alcohol present in essential oils of several aromatic plant species. Previous studies indicate that linalool is a valuable compound with a wide range of therapeutic properties. The promising therapeutic effects of linalool are however limited by its poor water solubility and volatility. Recently, the encapsulation of linalool in drug delivery systems, such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) has demonstrated to overcome linalool physicochemical limitations. The present study aimed the production and optimization of linalool encapsulation in SLN applying the experimental full factorial design. The estimation of the long-term stability of the produced linalool-loaded SLN was carried out using a new centrifugal sedimentation method, LUMiSizer®. SLN dispersions were produced by the hot high pressure homogenization (HPH) method. The influence of the independent variables, surfactant and lipid concentrations on linalool-loaded SLN particle size, polydispersity index (PI) and zeta potential (ZP) was evaluated by a 22 factorial design composed of 2 variables which were set at 2-levels each. For each of the three dependent variables, analysis of the variance (ANOVA) was performed using a 95% confidence interval. The concentration of surfactant, as well as, the interaction between the different concentrations of lipid and surfactant, hada statistically significant effect on the particle size and PI. Experimental factorial design has been successfully employed to develop an optimal SLN dispersion, requiring a minimum of performed experiments. Based on the obtained results, the optimal linalool-loaded SLN dispersion was composed of 1% (w/v) linalool 2% (w/v) of solid lipid and 5% (w/v) of surfactant. Furthermore, the stability analysis revealed that the produced linalool-loaded SLN dispersions have limited storage stability which can be easily overcome through the assembly of a polymeric coating on the SLN surface. LUMiSizer® has been successfully used in the kinetic analysis of linalool-SLN during accelerated storage time.
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