Cubosomes and hexosomes have generated great attention as they are the first to have molecular, multilevel, mesophasic, and nanoparticle observed structural compounds. They can be administrated through various routes thus providing versatility in the administration of various drugs. Internal structure defined before dispersion by liquid crystal mesophases of amphiphiles offers complex topologies; they can carry a higher volume of drug with long-term release [75]. Size ranges vary in the nanometer range, which allows similar surfactant to uniformly distribute and prevent aggregation. Since it possesses the curvature in the internal structure of crystalline mesophases, large volume of the drug can be loaded, which increases the potential for drug targeting [76, 77]. Due to the amphiphilic nature of liquid crystal forming lipid (polar head and lipophilic tail), they arrange themselves into a cubic or hexagonal phase, which is thermodynamically stable. Therapeutic applications of liquid crystal nanoparticles (cubosomes and hexagonal) are associated with the drug, route of delivery, formulation, and physiochemical properties such as increased molecular weight, the different polarity of drug molecule, compatibility issue, enzymatic degradation, and reduced toxicity.
1.4 Methods of Preparation of Lipid Nanocarriers
There are various high energy input and low energy input methods available for the preparation of lipid-based nanocarriers. The methods presented here include physical ones like homogenization and chemical ones like co-acervation. The choice of methods and energy input depends on the thermal stability of lipid molecules as well as drug molecule. Several important methods utilized for the preparation of lipid nanocarriers are given in Table 1.3.
1.5 Challenges and Hurdles
1.5.1 Scale Up and Stability Issues
The development of the lipid-based nanocarrier system can easily be scaled using the reported approach for preparation. Several issues of stability can, however, be associated with lipid carriers and can be a hurdle in the process of the scale-up. Polymorphism must first be taken into account. The colloidal size and particularly their high volume-to-surface ratio can result in the decrease in melting points. This effect may also be caused by impurities, agents, and stabilizers [86, 87]. For example, the co-acervation and hot homogenization method of fatty acids and triglycerides results in polymorphism [88]. Due to rapid solvent evaporation, polymorphic forms have been obtained during spray drying.
Table 1.3 Different types of techniques used in the preparation of lipid nanocarriers.
| Preparation techniques | Description | References | |
| High-pressure homogenizationPressure: 100–2000 bar | Hot homogenization | Drug melted in hot lipid Pressure: 500–1500 bar Production of nanoemulsion | [78, 79] |
| Cold homogenization | Suitable for thermosensitive drug.Formulation rapidly cooled in dry ice. | ||
| Ultrasonication | Probe ultrasonication | Use for oral drug delivery systems.Diameter range: 80–800 nmReduce shear stress. | [80] |
| Bath ultrasonication | |||
| Solvent emulsification–diffusion method | Lipid dissolved in organic solvents (chloroform, ethyl acetate, methylene chloride, cyclohexane).Use for hydrophilic drug (w/o/w emulsion).Diameter range: 30–100 nm. | [81] | |
| Supercritical fluid method | Lipophilic substances dissolved in organic solvent.Nanoparticle range 25 nm.Solvent removal by evaporation (pressure 40–60 mbar). | [82] | |
| Microemulsion-based method | Two-phase system inner and outer (o/w microemulsion)Lower mechanical energy.Increased drug loading capacity, range of 200–250 nm. | [82] | |
| Spray drying method | |||