Biology

Dr. Chandra Haas
Department of Chemical Engineering Nanotechnology Lab (#220/222) Indian Institute of Technology Bombay Powai, Mumbai

Abstract:

Liposomes (or vesicles), which are spherical lipid bilayers, are used for drug delivery. Especially, monodisperse unilamellar vesicles of size less than 200 nm are preferred for a predictable pharmacokinetic/ pharmacodynamic drug release profile. The size and size distribution of liposomes are the crucial parameters in determining the amount of encapsulant that can be delivered. Preparing liposomes by changing the organic solvent (containing the lipids) conditions with the contact of water is a popular class of technique.
This technique has several variations and among them, alcohol injection is one of the simplest ways to produce SUVs. However, a poor control on the size distribution is a major issue with this method. Recently, a new principle, termed Stationary phase interdiffusion (SPI), was introduced by which it is possible to obtain monodisperse unilamellar vesicles in a single step without requiring any size-reduction or other processing. In this work, we extend the application of this method and further the fundamental understanding on an observed
anomalous phenomenon.

To overcome a long time of several hours ( 6 h) taken for liposomes formation in the earlier proposed device and method (studies done in vertical cuvette setup), we introduce an alternate horizontal capillary setup that significantly reduces the liposome preparation time to about 10 min. The stationary interface between a lipid-ethanol phase and an aqueous phase is created by a density difference induced convective flow in a horizontal capillary. The average size of the liposomes is modulated only by the temperature and the type of lipids. This simple methodology provides a rapid production tool for researchers requiring reproducible liposome suspensions.

In the vertical cuvette setup, certain reproducible but anomalous finger-like patterns (made of vesicles) are observed. Finger-like patterns by a phenomenon known as viscous fingering, generally occur in an interface when a lower viscous or higher dense fluid is pushed through another miscible or immiscible fluid having higher viscous or lower dense one, and such phenomena are well described by the Saffman-Taylor instability theory. Unlike in the well-defined viscous fingering case, the lipids have a lower bulk density and higher viscosity
as compared to the aqueous phase. We test various hypotheses to explain this behavior: (a) diffusiophoretic velocity driven particles in a viscosity stratified medium, and (b) aggregation followed by gravity driven settling. We show by carefully selected systems that the fingers formation occurs mainly by the particle aggregation not by diffusiophoresis phenomena.