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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.