Cubic phase gels as drug delivery systems

Abstract

Lipids have been used extensively for drug delivery in various forms such as liposomes, and solid-matrices. The focus of this review is evaluation of liquid crystalline cubic phases, spontaneously formed when amphiphilic lipids are placed in aqueous environment, for drug delivery. Cubic phases have an interesting thermodynamically stable structure consisting of curved bicontinuous lipid bilayer in three dimensions, separating two congruent networks of water channels. The unique structure of cubic phase has been extensively 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 release 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 drugs and large proteins by oral and parenteral routes in addition to local delivery in vaginal and periodontal cavity. A number of different proteins in cubic phase appear to retain their native conformation and bioactivity, and are protected from chemical and physical inactivation perhaps due to the reduced activity of water and biomembrane-like structure of cubic phase. Release of drugs from cubic phase typically show diffusion controlled release from a matrix as indicated by Higuchi’s square root of time release kinetics. Incorporation of drug in cubic phase can cause phase transformation to lamellar or reversed hexagonal phase depending on the polarity and concentration 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 incorporated drugs and proteins make the cubic phase gel an excellent candidate for use as a drug delivery matrix. However, shorter release duration and the extremely high viscosity may limit its use to specific applications such as periodontal, mucosal, vaginal and short acting oral and parenteral drug delivery.