Cubic phases drug delivery

Cubic Phases as Delivery Systems for Peptide Drugs... 

B. Ericsson, P.O. Eriksson, J.E. Lofroth, S. Engstrom, Cubic Phases as Delivery Systems for Peptide Drugs, Polymeric Drugs and Drug Delivery System (American Chemical Society, Washington, DC, 1991), pp. 251-265... 

In this work we will focus on the use of the cubic phase as a delivery system for oligopeptides - Desmopressin, Lysine Vasopressin, Somatostatin and the Renin inhibitor H214/03. The amino acid sequences of these peptides are given in Table I. The work focuses on the cubic phase as a subcutaneous or intramuscular depot for extended release of peptide drugs, and as a vehicle for peptide uptake in the Gl-tract. Several examples of how the peptide drugs interact with this lipid-water system will be given in terms of phase behaviour, peptide self-diffusion, in vitro and in vivo release kinetics, and the ability of the cubic phase to protect peptides from enzymatic degradation in vitro. Part of this work has been described elsewhere (4-6). 

ERICSSON ET AL. Cubic Phases as Drug Delivery Systems... 

The components can be chosen so that the material is biocompatible, opening up possibilities for use in controlled-release drug-delivery and other medical and biological applications that call for nontoxicity. It is known that many biological lipids form bicontinuous cubic phases, and many of these have modifications with polymerizable groups, such as the monolinolein case discussed above. 

A liquid crystal is a general term used to describe a variety of anisotropic structures formed by amphiphilic molecules, typically but not exclusively at high concentrations. Hexagonal, lamellar, and cubic phases are all examples of liquid crystalline phases. These phases have been examined as drug delivery systems because of their stability, broad solubilization potential, ability to delay the release of encapsulated drug, and, in the case of lamellar phases, their ability to form closed, spherical bilayer structures known as vesicles, which can entrap both hydrophobic and hydrophilic drug. This section will review SANS studies performed on all liquid crystalline phases, except vesicles, which will be considered separately. Vesicles will be considered separately because, with a few exceptions, generally mixed systems, vesicles (unlike the other liquid crystalline phases mentioned) do not form spontaneously upon dispersal of the surfactant in water and because there have been many more SANS studies performed on these systems. 

Glyceryl monooleate gels in excess water, forming a highly ordered cubic phase that can be used to sustain the release of various water-soluble drugs.It is also the basis of mucoadhesive drug delivery systems. 

Wyatt DM, Dorschel D. Cubic-phase delivery system composed of glyceryl monooleate and water for sustained release of water-soluble drugs. Pharm Technol 1992 16 116-130. 

Longer M, Tyle P, Mauger JW. A cubic-phase oral drug delivery for controlled release of AG 337. Drug Dev Ind Pharm 1996 22 603-608. 

Chang CM, Bodmeier R. Low viscosity monoglyceride based drug delivery systems transforming into a highly viscous cubic phase. Int Pharm 1998 173 51-60. 

Shah, J.C., Sadhale, Y. and Chilukuri, D.M., Cubic phase gels as drug delivery systems, Advanced Drug Delivery Reviews, 2001, 47, 229-250. 

Chang C-M, Bodmeier R. Effect of dissolution media and additives on the drug release from cubic phase delivery systems. Journal of Controlled Release. 1997 46(3) 215-222. 

J.C. Shah, Y. Sadhale, M.C. Dakshina, Cubic phase gels as dmg delivery systems. Adv. Drug Deliv. Rev. 47, 229-250 (2001)... 

J. Bender, M.B. Ericson, N. Merclin, V. lani, A. Rosen, S. Engstrom, J. Moan, Lipid cubic phases for improved topical drug delivery in photodynamic therapy. J. Control. Rel. 106, 350-360 (2005)... 

There are a number of liquid crystalline phases formed by amphiphilic molecules, notably surfactants, polar lipids and block copolymers, including discrete and bicontinuous cubic phases, hexagonal phases (and their reversed counterparts), lamellar phases, intermediate phases, etc. A number of these phases are interesting from a drug delivery point of view. This is due to the frequently large solubilization capacity of both hydrophilic and hydrophobic substances, possibilities to control the drug release rate, favourable rheological properties, suitable water transport rates, excellent stability, etc. 

Engstrom, S., Drug delivery from cubic and other lipid-water phases. Lipid Technol, 2, 42-45 (1990). 

---