Cubic phase gels as drug delivery systems

Lipids have been used extensively for drug delivery in various forms such a s liposomes, and solid-matrices. The focus of this review is evaluation of liquid crystalline cubic phases, spontaneously formed when amphiphilic lipi ds are placed in aqueous environment, for drug delivery. Cubic phases have an interesting thermodynamically stable structure consisting of curved bico ntinuous lipid bilayer in three dimensions, separating two congruent networ ks of water channels. The unique structure of cubic phase has been extensiv ely studied using various spectroscopic techniques and their resemblance to biomembranes has prompted many scientists to study behavior of proteins in cubic phases. The ability of cubic phase to incorporate and control releas e of drugs of varying size and polar characteristics, and biodegradability of lipids make it an interesting drug delivery system for various routes of administration. Cubic phases have been shown to deliver small molecule dru gs and large proteins by oral and parenteral routes in addition to local de livery in vaginal and periodontal cavity. A number of different proteins in cubic phase appear to retain their native conformation and bioactivity, an d are protected from chemical and physical inactivation perhaps due to the reduced activity of water and biomembrane-like structure of cubic phase. Re lease of drugs from cubic phase typically show diffusion controlled release from a matrix as indicated by Higuchi's square root of time release kineti cs. Incorporation of drug in cubic phase can cause phase transformation to lamellar or reversed hexagonal phase depending on the polarity and concentr ation of the drug, which may affect the release profile. Biodegradability, phase behavior, ability to deliver drugs of varying sizes and polarity and the ability to enhance the chemical and/or physical stability of incorporat ed drugs and proteins make the cubic phase gel an excellent candidate for u se as a drug delivery matrix. However, shorter release duration and the ext remely high viscosity may limit its use to specific applications such as pe riodontal, mucosal, vaginal and short acting oral and parenteral drug deliv ery. (C) 2001 Elsevier Science B.V, All rights reserved.