Cubic phase gels as drug delivery systems
Introduction
Lipids of various types have been extensively studied for drug delivery by different routes of administration. Relatively hydrophobic lipids in the solid state have been used primarily as matrix material as carriers of hydrophilic drugs to provide sustained release orally and as a drug delivery carrier in solid implants. Amphiphilic polar lipids such as phospholipids when placed in water spontaneously forms thermodynamically stable lipid bilayers, which can assume various geometric shapes and structures. Liposome is one such example in which, amphiphilic lipids reorganize into closed circular lipid bilayers enclosing an aqueous phase, and they have been extensively studied for drug, protein and gene delivery. However, the spontaneous reorganization of amphiphilic lipids in aqueous environment can result in other three-dimensional structures such as the lamellar phase, the cubic phase, and transferosomes, which can be used for, drug delivery [1], [2], [3]. The structure of cubic phase has generated a lot of interest and is yet another exciting lipid-based system beginning to be explored for drug, protein and vaccine delivery [1], [2], [3], [4]. We will attempt to briefly review the origin, structure and phase behavior of cubic phase, followed by common techniques used to study cubic phases. The introduction to cubic phase will be followed by examining studies on drug delivery attempts using cubic phases and critically evaluate the potential of cubic phase as delivery system.
Section snippets
Phase behavior of amphiphilic lipids forming cubic phase
Polar amphiphilic lipids such as glyceryl monooleate (GMO) when placed in water reorganize into lipid bilayers forming a reversed micellar phase (L2) and three types of liquid crystalline phases (lamellar, reversed hexagonal and the cubic phase) depending upon the temperature and water content as shown in the phase diagram shown in Fig. 1 [1], [2], [4], [5]. The lamellar (Lα) phase has a long-range order in one dimension. Its structure consists of a linear arrangement of alternating lipid
Structure of cubic phases
The schematic structure of the cubic phase mentioned in the phase diagram is shown in Fig. 2 [1], [2], [4], [5]. Structure of the cubic phase is unique and consists of a curved bicontinuous lipid bilayer extending in three dimensions, separating two congruent networks of water channels. The water pore diameter of the fully swelled phase is about 5 nm and the phase is very viscous. The unique curvature of the bilayer as in the cubic phase is associated with an energy known as the curvature
Cubic phase as drug delivery system
As seen from above novel applications of cubic phase in recent articles, its unique structure has generated a lot of interest and is being studied as a model for physiological lipid membrane and how that influences the structure and activity of incorporated proteins. In contrast, very few researchers have shown interest in cubic phase gel for drug delivery, in spite of cubic phase possessing desirable physico-chemical properties for drug delivery [4], [29], [38], [39]. Almost all of the reports
Chemical stability enhancement in cubic phase gel
Ericsson et al. [4] in their first article on delivery of oligopeptides from cubic phase gel observed that the cubic phase protected the peptides from enzymatic degradation. The rate of enzymatic degradation of the renin inhibitor H214/03 in the cubic phase was 5.7% of that in a homogeneous solution representing intestinal fluids. The degradation rates were mainly dependent on the release rate of the peptide from the cubic phase to the surface during the experiment. H214/03, being a hydrophobic
Phase behavior and release characteristics of cubic phase gel
Very little is known about the degrees of freedom in cubic phase systems with respect to release duration, phase transformations, drug–bilayer interactions and rheological property and its impact on practical issues such as injectability. For the cubic phase system to be developed as an effective arsenal in drug delivery field, more research on the physical chemistry of cubic phase, and a basic understanding of the phase diagram and release kinetics and mechanism is required. Furthermore,
Potential of cubic phases as delivery systems and future direction
The unique structure and physicochemical properties of liquid crystalline cubic phase gel makes it suitable as a drug delivery matrix. The ability to incorporate and slowly release a variety of drugs with different physicochemical properties by a variety of routes of administration has been demonstrated. The similarity of cubic phase to physiological lipid membranes and its ability to incorporate and maintain protein in their native bioactive conformation is a unique attribute, extremely
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- 1
Present address: Pentech Pharmaceuticals, 417 Harvester Court, Wheeling, IL 60090, USA.
- 2
Present address: Genzyme Corporation, 45 New York Avenue, P.O. Box 9322, Framingham, MA 01701-9322, USA.