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      Cubic and Hexagonal Liquid Crystals as Drug Delivery Systems


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          Lipids have been widely used as main constituents in various drug delivery systems, such as liposomes, solid lipid nanoparticles, nanostructured lipid carriers, and lipid-based lyotropic liquid crystals. Among them, lipid-based lyotropic liquid crystals have highly ordered, thermodynamically stable internal nanostructure, thereby offering the potential as a sustained drug release matrix. The intricate nanostructures of the cubic phase and hexagonal phase have been shown to provide diffusion controlled release of active pharmaceutical ingredients with a wide range of molecular weights and polarities. In addition, the biodegradable and biocompatible nature of lipids demonstrates the minimum toxicity and thus they are used for various routes of administration. Therefore, the research on lipid-based lyotropic liquid crystalline phases has attracted a lot of attention in recent years. This review will provide an overview of the lipids used to prepare cubic phase and hexagonal phase at physiological temperature, as well as the influencing factors on the phase transition of liquid crystals. In particular, the most current research progresses on cubic and hexagonal phases as drug delivery systems will be discussed.

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          Most cited references102

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          Cubic lipid-water phases: structures and biomembrane aspects

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            Cubic phase gels as drug delivery systems.

            J. Shah (2001)
            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.
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              Surfactant self-assembly objects as novel drug delivery vehicles


                Author and article information

                Biomed Res Int
                Biomed Res Int
                BioMed Research International
                Hindawi Publishing Corporation
                5 June 2014
                : 2014
                1Department of Pharmaceutics, College of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui 230031, China
                2Global Pharmaceutical Research and Development, Hospira Inc., 1776 North Centennial Drive, McPherson, KS 67460, USA
                3Anhui Key Laboratory of Modern Chinese Medicine & Materia, Hefei, Anhui 230031, China
                4Anhui “115” Xin'an Traditional Chinese Medicine Research & Development Innovation Team, Hefei, Anhui 230031, China
                Author notes

                Academic Editor: Sergio Murgia

                Copyright © 2014 Yulin Chen et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Funded by: http://dx.doi.org/10.13039/501100001809 National Natural Science Foundation of China
                Award ID: 81274099
                Funded by: Natural Science Foundation of Anhui Province
                Award ID: 11040606M219
                Funded by: Natural Science Foundation of the Anhui Higher Education Institutions of China
                Award ID: KJ2012A184
                Funded by: Foundation of Anhui University of Chinese Medicine
                Award ID: 201303
                Review Article


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