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Liposomes and Vesicles

   Vesicles are closed amphiphile membrane capsules consisting of single or multiple lamellae (which are usually bilayers, but are sometimes monolayers of bipolar or bolaform amphiphiles) of non-covalently assembled amphiphilic molecules in aqueous media.  When composed of natural phospholipids, vesicles are oftentimes called liposomes.  Liposomes have been used extensively as models for the study of biological membrane structure and function.  In addition, both natural and synthetic amphiphile vesicles have been investigated for use in drug and gene delivery and targeting, medical imaging, catalysis, energy conversion  and separations.  Vesicle or liposome technology is a rapidly evolving field of inquiry in both the basic and applied sciences and engineering.  In addition, there are now several industrial organizations engaged in researching and developing processes and products derived from vesicular materials.

    Owing to their utilization in many scientific inquiries and technological applications there has been a strong driving force for the development of non invasive, accurate and economical methods for the characterization of liposome dispersions, and, more generally, polymer, surfactant and biomolecular fluids.  For the analysis of experimental data and potential applications of these systems, a minimum of size, shape, polydispersity and dynamic properties is needed to determine the total surface area, encapsulated volume and stability of the vesicular dispersion or complex fluid.

    Suspensions of self-assembled surfactant aggregates, such as micelles, vesicles, microemulsions and lamellar or sponge phases, can be characterized by a variety of techniques such as: electron microscopy, force microscopy, analytical ultracentrifugation, sedimentation flow field fractionation, viscometry, NMR spectroscopy, gel chromatography and various scattering techniques.  Microscopies offer the advantage of visualization in real space, as opposed to Fourier space in the case of scattering techniques, and therefore are of greatest value when it is suspected that the suspension consists of surfactant aggregates of unusual shape and widely varying size.  These techniques, however, require the surfactant aggregates to be analyzed outside of their true aqueous environment and sample preparation protocols may lead to artifacts.  The other characterization techniques, including those based on scattering methods, are best applied when the surfactant aggregates are somewhat homogeneous in size and shape or when the dynamics of the system are under investigation.

    Our research group has worked extensively on developing static light scattering or multiangle laser light scattering (MALLS) techniques for liposome/vesicle characterization.  MALLS measurements indicate that liposomes scatter light  within the Rayleigh-Gans-Debye (RGD) approximation, which greatly facilitates the analysis of MALLS spectra [van Zanten & Monbouquette (1991); van Zanten and Monbouquette (1994)]. [Insert Figure]  MALLS is particularly powerful in that one can determine both a geometric size as well as a molar mass.  Owing to the essentially insoluble nature of double-tailed phospholipids (CMCs < 10^-9 M), liposome dispersions can be diluted within a fairly broad concentration range (several factors) with very little, if any, change in the mass distribution of the phospholipids.  Serial dilutions allow the application Zimm's graphical technique for determining the mean-square radius, molar mass and second virial coefficient of phospholipid dispersions [van Zanten & Monbouquette (1991)].  [insert figure]  One can also utilize simple geometric modeling to estimate liposome wall thickness from light scattering measurements for the case of near size monodisperse liposome size dispersions [van Zanten (1994)].  Owing to its sensitivity to different moments of the size distribution, Zimm's (Debye's) graphical technique can also be used to determine the degree of size polydispersity present in liposome dispersions [van Zanten (1995)].  However, when it is expected that the liposome size distribution is very broad, it is best that such size distributions are determined from a coupled fractionation-MALLS scheme [Korgel, van Zanten & Monbouquette (1998)].  Our current efforts in the liposome/vesicle area focus on monitoring liposome-liposome aggregation and fusion.

Current and Past Group Members

    K. Wang, E. Lai, ('96-'01), R.M. Konecny ('95-'97), S.K. Murthy ('96-'99), D.C. Nevoret ('96-'98), D.E. Ortelli ('96-'98), V.A. Pferdeort ('97-'99)

Current and Past Collaborators

    A. Singh, A. Annapragada ('96-'98), M. Kennedy ('98), B.A. Korgel ('97-'98), H.G. Monbouquette ('87-'92, '97-'98), J.A.N. Zasadzinski ('98)

Publications to Date

• B.A. Korgel, J.H. van Zanten & H.G. Monbouquette, "Measurement of Vesicle Size Distributions Using Field Flow Fractionation Coupled with On-Line Static Light Scattering", Biophys. J.74, 3264-3272 (1998).
• J.H. van Zanten, "Characterization of Vesicles and Vesicular Dispersions via Scattering Techniques", In Vesicles (edited by Morton Rosoff), Surfactant Science Series Volume 62 (Marcel-Dekker, New York, 1996), pages 239-294.
• J.H. van Zanten, "The Zimm Plot and Its Analogues as Indicators of Vesicle and Micelle Size Polydispersity", J. Chem. Phys.102, 9121-9128 (1995).
• J.H. van Zanten, D.S.-W. Chang, I. Stanish & H.G. Monbouquette, "Selective Extraction of Pb²⁺ by Metal-Sorbing Vesicles Bearing Ionophores of a New Class", J. Membrane Sci.99, 49-56 (1995).
• J.H. van Zanten, "Unilamellar Vesicle Radii and Wall Thicknesses Determined by Zimm's Light Scattering Technique", Langmuir10, 4391-4393 (1994).
• J.H. van Zanten & H.G. Monbouquette, "Phosphatidylcholine Vesicle Diameter, Molecular Weight and Wall Thickness Determined by Static Light Scattering", J. Coll. Interface Sci.165, 512-518 (1994).
• J.H. van Zanten & H.G. Monbouquette, "Biomimetic Metal-Sorbing Vesicles: Cd²⁺ Uptake by Phosphatidylcholine Vesicles Doped with Ionophore A23187", Biotech. Prog.8, 546-552 (1992).
• J.H. van Zanten & H.G. Monbouquette, "Characterization of Vesicles by Classical Light Scattering", J. Coll. Interface Sci.146, 330-336 (1991).

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