Smectic nanoparticles

Liquid crystalline phases, also called mesophases, bear a high potential in drug delivery which may be further extended by their use in nanoparticulate form. This chapter describes the different types of nanoparticles based on lyotropic and thermotropic mesophases, like cubosomes, hexosomes and supiercooled smectic nanoparticles. 

The high supercooling tendency of the smectic phase of cholesterol esters is the basis for the development of smectic nanoparticles from cholesterol esters that are crystalline solids in the bulk at... 

Figure 10.9. DSC heating and cooling curves (5°C/min) of cholesteryl myristate in the bulk and in colloidal dispersion (5% CM, 2% PVA PCS z-average 172 nm, PDI 0.09). With kind permission from Springer Science + Business Media Fharm. Res. Supercooled smectic nanoparticles A potential novel carrier system for poorly water soluble drugs, 21, (2004), 1834-1843, J Kuntsche et al. Abbreviations DSC differential scanning calorimetry, PVA polyvinyl alcohol, PCS Photon correlation spectroscopy, PDI Polydispersity index.

However, high pressure melt homogenization presents a distinct thermal stress for the formulation and thermally sensitive compounds and drugs may be degraded. If thermal stress is an issue for the respective formulation, the so-called solvent-evaporation method can be used as an alternative. The whole preparation process is carried out at room or slightly lower temperature. By this preparation method, smectic nanoparticles with a mean size distinctly below 100 nm can be obtained. A disadvantage of this method are potential residues of the organic solvent in the final formulations. 

Electron microscopic investigations (cryo-TEM and freeze-fracture ) indicate that supercooled smectic nanoparticles have a nearly cylindrical particle shape in most cases. This is in agreement with the cylindrical shape of LDL when studied at room temperature where the LDL are in a liquid crystalline state. ... 

In dispersions stabilized on the basis of phospholipids, an additional fraction of very unstable particles was detected in the cryo-preparation. These particles possibly have a spherical shape as particles with an onion-like structure were detected in the freeze-fracture preparations. Due to the layered structure of the smectic phase, a cylindrical particle shape should be energetically more favorable than a spherical one. This may also be the reason for the higher sensitivity of spherical particles towards the electron beam. In formulations with polymeric stabilizers (e.g. poloxamer, polyvinyl alcohol and Tween 80), such highly unstable particles have not been detected yet. Polymer-stabilized smectic nanoparticles possess a more round, paving-stone-like particle shape. In dependence on the stabilizer system, additional colloidal structures (e.g. vesicles and micelles) formed by the excess of emulsifiers could be detected as well (Fig. 10.11). 

Smectic nanoparticles that do not crystallize upon long-term storage at 23°C and retain the smectic state at body temperature could be prepared by admixtures of cholesterol esters with a lower... 

Compared to lyotropic LCNP the thermotropic mesophase-based supercooled smectic nanoparticles are in a still much more early stage of development. Although structural aspects of these nanoparticles are not quite as complex as with lyotropic LCNP and the physicochemical properties of these nanoparticles as well as the influencing parameters on the phase behavior have been studied in some detail yet much remains to be done for further optimization of the formulations in particular with regard to the stability of the nanoparticles against recrystallization. Furthermore, application related studies have to be performed, especially with a focus on parenteral drug delivery which was the main driving force for the development of these particles. 

Several other nanomaterials (e.g., silica nanoparticles) have been studied predominantly as dopants for nematic or smectic liquid crystal phases [278-287], but we decided to limit the discussion above to the major types receiving significantly more attention over the last few... 

Zero-Dimensional Nanoparticle Additives in Smectic Phases... 

In comparison to nematic liquid crystals, examples of smectic liquid crystals doped with quasi-spherical nanoparticles became more elusive over the last few years. This is surprising especially considering recent work by Smalyukh et al., who found that nanoscale dispersion (based on /V-vinyl-2-pyrrolidone-capped gold nanoparticles with 14 nm diameter) in a thermotropic smectic liquid crystal (8CB) are potentially much more stable than dispersions of nanoparticles in nematics [367]. 

Earlier work on nanoparticle-doped chiral smectic-A (SmA ) and chiral smec-tic-C (SmC ) phases including some intriguing electro-optic effects in ferroelectric SmC phases were summarized in two earlier reviews [1, 2],... 

Finally, an area that will most likely see an explosive growth over the next few years is the self-assembly of nanoparticles covered with mesogenic and pro-mesogenic capping agents. A number of different approaches have been summarized in this review, and the formation of nematic, smectic-like, cubic, and columnar phases and/or superstructures have been demonstrated. Once more, the possibilities to produce such metamaterials using nanoparticles and liquid crystal motifs are endless, and future research will surely discover other, in part, more complex phase morphologies as well as uniquely tunable nanoscale properties as a result of liquid crystal phase formation. 

Three different ways have been developed to produce nanoparticle of PE-surfs. The most simple one is the mixing of polyelectrolytes and surfactants in non-stoichiometric quantities. An example for this is the complexation of poly(ethylene imine) with dodecanoic acid (PEI-C12). It forms a solid-state complex that is water-insoluble when the number of complexable amino functions is equal to the number of carboxylic acid groups [128]. Its structure is smectic A-like. The same complex forms nanoparticles when the polymer is used in an excess of 50% [129]. The particles exhibit hydrodynamic diameters in the range of 80-150 nm, which depend on the preparation conditions, i.e., the particle formation is kinetically controlled. Each particle consists of a relatively compact core surrounded by a diffuse corona. PEI-C12 forms the core, while non-complexed PEI acts as a cationic-active dispersing agent. It was found that the nanoparticles show high zeta potentials (approximate to +40 mV) and are stable in NaCl solutions at concentrations of up to 0.3 mol l-1. The stabilization of the nanoparticles results from a combination of ionic and steric contributions. A variation of the pH value was used to activate the dissolution of the particles. 

A parameter that cannot be over looked is the dispersity in size of the particles. Indeed, polydispersity usually prevents long range positional ordering. For example, it is crucial in order to obtain (i) smectic phases to have nanoparticles of fairly homogeneous length and (ii) hexagonal phases to have nanoparticles with diameters as monodisperse as possible. 

Furthermore, this smectic nanoporous network could be used as reaction medium, for instance for the formation of silver nanoparticles (NPs) [78]. The pores were first filled with silver ions and subsequently the ions were reduced to form Ag nanoparticles. The NPs are monodisperse (Fig. 2.20) [78], and interestingly, the size... 

Fig. 2.20 TEM image along with the particle size distribution of an ultramicrotomed section of a planar Ag nanoparticle smectic hybrid film as shown in Fig. 2.18. Adapted with the permission from Ref [78]. Cop5uight 2013 American Chemical Society...

Because the layers of LCs transmit elastic energy, they can be used to do mechanical work, such as to assemble nanomaterials and induce topological defects in LCs. The feasibility of this scheme has been illustrated in the lab scale. For instance, linear and hexagonal arrays of nanoparticles were elastically trapped at various sites of smectic defects. Single wall carbon nanotubes could be organized into 2D parallel sheets between smectic layers due to specific interactions between n and n interactions between the hexagonal rings of the carbon nanotubes and the aromatic moieties of LC molecules [62, 67, 71]. 

R. Pratibha, W. Park, LI. Smalyukh, Colloidal gold nanosphere dispersions in smectic liquid crystals and thin nanoparticle-decorated smectic films. J. Appl. Phys. 107, 63511 (2010)... 

---