Anales RANF

Nannocannabinoids for brain tumor drug delivery @Real Academia Nacional de Farmacia. Spain 203 evidenced herein that the oily phase/surfactant mass ratio is the major parameter that drives nanocapsule formation for different oil-surfactant combinations (namely, Labrafac ® WL1349-Kolliphor ® HS15, Labrafac ® WL1349-Kolliphor ® ELP, Labrafil ® M 1944 CS- Kolliphor ® HS15). These combinations exhibit distinct oil/surfactant affinities as summarized in Table 3 in terms of HLB. The plot of the average volume diameters versus the oil/surfactant ratio was linear within the ratio range between 0.08 and 3 and this linear trend is consistent through the distinct surfactant-oil affinities. According to the high coefficients of determination observed (R 2 >0.99), these univariate linear mathematical models are well- suited to predict the particle size of the nanocapsules prepared by the PIT method. As hypothesized, particle size increased along with the oil/surfactant ratio: higher ratios represent a decrease in surfactant relative concentration, and ultimately lead to bigger capsules. The estimation of particle size with a univariate mathematical model is of the greatest importance as it will intuitively teach formulators how to tailor particle size of LNCs prepared by the PIT method to the therapeutic needs imposed by a specific disease. Highly monodisperse LNCs were obtained in all cases: the polydispersity indexes (PdI) were maintained under 0.06, regardless the particle size, well below the most broadly used upper limit for monodisperse criteria of 0.1. Figure 1: Univariate linear regression between the average volume diameter and the oil/surfactant mass ratio of LNCs prepared by the PIT method. Table 2: Parameters of the univariate linear regression between the average volume diameter and the oil/surfactant mass ratio for the different combinations tested. Oil/surfactant tandem Y-intercept Slope R 2 Labrafac ® lipophile WL1349- Kolliphor ® HS15 8.83 28.16 0.9983 Labrafac ® lipophile WL1349- Kolliphor ® ELP 9.59 22.13 0.9996 Labrafil ® M 1944 CS- Kolliphor ® HS15 11.23 11.11 0.9939 Table 3: HLB values of the different oily phases and polyethoxylated surfactants as declared by suppliers. Excipient HLB value Labrafac ® lipophile WL1349 1 Labrafil ® M 1944 CS 9 Kolliphor ® ELP 13 Kolliphor ® HS15 15 Importantly, a comparison among the linear plots for the different oil-surfactant tandems can be drawn. On the one hand, there are not statistically significant differences in the Y-intercept (Table 2), which means that there exists a lower limit of particle size to be obtained with the PIT method and this limit equals 10 nm. On the other hand, we