SLNs were prepared by the method named “cold dilution of microemulsion” [17 (link)]; briefly, a preliminary screening on several compositions was performed, operating at room temperature, to obtain the suitable O/W µE whose disperse phase consisted in a solution of a solid lipid dissolved in a partially water miscible solvent. The solvent and the external phase, consisting of water, were mutually saturated at 25 ± 2 °C for 2 h in order to ensure the initial thermodynamic equilibrium of both liquids, before using them in µE formulation. Lipid nanoparticles were precipitated by quickly adding 5 mL of water into the µE (1 mL) to remove the solvent from the disperse phase and extract it into the continuous phase.
µEs were obtained with biocompatible GRAS ingredients (Generally Recognized As Safe). Among different lipids tested (TL, trimyristin, tristearin, myristic acid, glyceryl dibehenate, and glyceryl monostearate), a TL solution in EA was chosen as oil phase, because of its highest solubility in this partially water-miscible solvent (Table 1 ). EA and water were mutually pre-saturated before using them in µE preparation (EAs and Ws respectively). BenzOH, TA, BL were also tested as partially water-miscible solvents (water saturated) to solubilize the lipid.
Epikuron® 200 was chosen as surfactant together with polysorbate (20, 40, 80) or Cremophor® RH 60 at 3:1 w/w constant ratio.
Na TdC, Na TC, Na GC, Na C were tested as co-surfactants, BenzOH was chosen as a co-solvent.
A formulation study was performed varying the percentages of surfactant and co-surfactant/co-solvent. The optimal µE formulation, in the absence of any drug, called µE1, is reported inTable 2 .
µE1 (1 mL) was then diluted with a 2% w/w polymeric aqueous solution (5 mL) to precipitate SLNs. In order to avoid SLN aggregation [16 (link)], different polymers (Cremophor® RH60, Pluronic® F68, PVA® 9000, PVA® 14000) and different percentages of Pluronic® F68 were tested to check the best conditions to obtain small and non-aggregated SLNs. Probably, the polymer disposition on SLN surface influences surface hydrophilicity and charge. A formulation study was then performed to optimize SLN size.
µEs were obtained with biocompatible GRAS ingredients (Generally Recognized As Safe). Among different lipids tested (TL, trimyristin, tristearin, myristic acid, glyceryl dibehenate, and glyceryl monostearate), a TL solution in EA was chosen as oil phase, because of its highest solubility in this partially water-miscible solvent (
Epikuron® 200 was chosen as surfactant together with polysorbate (20, 40, 80) or Cremophor® RH 60 at 3:1 w/w constant ratio.
Na TdC, Na TC, Na GC, Na C were tested as co-surfactants, BenzOH was chosen as a co-solvent.
A formulation study was performed varying the percentages of surfactant and co-surfactant/co-solvent. The optimal µE formulation, in the absence of any drug, called µE1, is reported in
µE1 (1 mL) was then diluted with a 2% w/w polymeric aqueous solution (5 mL) to precipitate SLNs. In order to avoid SLN aggregation [16 (link)], different polymers (Cremophor® RH60, Pluronic® F68, PVA® 9000, PVA® 14000) and different percentages of Pluronic® F68 were tested to check the best conditions to obtain small and non-aggregated SLNs. Probably, the polymer disposition on SLN surface influences surface hydrophilicity and charge. A formulation study was then performed to optimize SLN size.
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