Analysis of Liquid Crystalline Nanoparticles by Small Angle X-Ray Diffraction: Evaluation of Drug and Pharmaceutical Additives Influence on the Internal Structure
Section snippets
INTRODUCTION
Liquid crystals belong to a state of matter with properties between those of an atomic ordered solid and an isotropic liquid. A liquid crystal phase may have structural similarities found in crystalline solids, as well as some disorder, evidenced by the ease of flow, as found in liquids. The transition between different phases corresponds to the breaking of some symmetry and can be described in terms of the so-called order parameter. This parameter represents the extent to which the
Materials
Monoolein (Myverol® 18–99K), with 94.5% minimum monoglyceride, and 1.2% maximum of free glycerine and fatty acid was supplied by Quest (Norwich, New York). OA, PpIX, ClAlPc, ZnPc, and N-methyl-pyrrolidone (NMP) were obtained from Sigma (St. Louis, Missouri). Poloxamer 407, a polyoxyethylene (101 units)–polyoxypropylene (56 units) copolymer, was obtained from BASF (Florham Park, New Jersey). Merguard® 1200 (∼20% purified 1,2-dibromo-2,4-dicyanobutane in 2-phenoxyethanol) was obtained from Nalco)
Polarized Light Microscopy
The MO/OA/poloxamer 407/H2O system (8:2:1.35:88.65, w/w/w/w), MO/OA/NMP/poloxamer 407/H2O system (8:2:5.5:1.35:83.15, w/w/w/w), and the previous system containing PSs were characterized under a polarized light microscope (Axioplan 2 Image Pol microscope; Carl Zeiss, Oberkochen, Germany) before and after the sonication process used to disperse the bulk phase.
Dynamic Light Scattering
The unloaded and drug-loaded nanodispersions, with or without the thickening polymer, were analyzed by light scattering at 25°C using a
RESULTS
The bulk phase composed of the MO/OA/poloxamer 407/H2O system presented a fanlike structure, typical of a hexagonal phase, as observed by polarized light microscopy (Fig. 1a). The addition of NMP and the PSs to this bulk phase did not change the characteristics of the hexagonal phase, as observed in Figures 1b–1e. Macroscopically, the addition of the hydrophilic solvent (NMP) led to a gel with low viscosity and microscopically a hexagonal structure in equilibrium with excess water. The
DISCUSSION
Liquid crystalline nanodispersions have many important characteristics for drug delivery due to their controlled release property 21,22 improved skin penetration,7,8,23 stabilization,9 and solubilization capacity.21,24 However, these phases can suffer phase transitions1 and the development of such drug delivery systems must include considerations of their internal structure after the addition of drugs and additives commonly used by the pharmaceutical industries, such as preservatives and
CONCLUSION
The presence of PSs, preservative and thickening polymer in the HPNs proposed in this work, did not change the liquid crystalline structure of this drug delivery system. This is an important finding relating to the influence of drugs and additive on the structure of the liquid crystalline phase because their stability, ability to load drugs, and to interact with biomembranes is intimately related to the phase. Finally, the formulation studies were strongly supported by the characterization of
ACKNOWLEDGEMENTS
This study was funded by the Conselho Nacional de Pesquisa (Brazil) and the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Brazil; project #04/09465-7). Fábia C. Rossetti was the recipient of a FAPESP fellowship (project #04/05280-2).
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