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Thomas Mavromoustakos et al. (eds.), Supramolecules in Drug Discovery and Drug Delivery: Methods and Protocols,
Methods in Molecular Biology, vol. 2207, https://doi.org/10.1007/978-1-0716-0920-0_4,
© Springer Science+Business Media, LLC, part of Springer Nature 2021
Chapter 4
Aggregate Determination by Permeation Technique
Phennapha Saokham and Thorsteinn Loftsson
Abstract
Permeation technique is used to study molecular aggregation in aqueous solutions including formation of
cyclodextrin guest/host aggregates. Since only guest molecules, host molecules and guest/host aggregates that are smaller than the pore size of a given semipermeable membrane are able to permeate through
the membrane, negative deviation of permeation profiles indicates formation of guest/host aggregates or
self-aggregates. This chapter describes how the method is used to detect formation of nano-sized aggregates and to determine the critical aggregation concentration (cac) from permeation profiles of a guest
molecule.
Key words Inclusion complexes, Critical aggregation concentration (cac), Permeation, Aggregates
1 Introduction
Clear aqueous solutions can contain molecular aggregates with
diameter below the wavelength of visible light. Frequently these
aggregates and clusters are transient; that is, they are constantly
being formed and dissembled [1]. Thus, it can be difficult to detect
them through conventional methods like dynamic light scattering
(DLS). Molecular membrane permeation is a passive diffusion process as described by Fick’s law [2]. Herein, we demonstrate how
the permeation technique through semipermeable membranes is
used to study the formation of transient guest/host aggregates
(e.g., drug/cyclodextrin complex aggregates) and clusters (i.e.,
loosely connected molecular structures). This method is based on
permeation of aggregating molecules through semipermeable
membranes of different molecular weight cutoffs (MWCOs) [3–
9]. Donor solutions (i.e., the test solutions) containing various
concentrations of, for example, guest/host aggregates or selfaggregates are placed in the donor chamber of Franz diffusion cells
(Fig. 1) [3–8] or miniature dialysis devices such as microequilibrium dialysis device (Fig. 2) [10] or cuplike MINI dialysis
Thomas Mavromoustakos et al. (eds.), Supramolecules in Drug Discovery and Drug Delivery: Methods and Protocols,
Methods in Molecular Biology, vol. 2207, https://doi.org/10.1007/978-1-0716-0920-0_4,
© Springer Science+Business Media, LLC, part of Springer Nature 2021
Chapter 4
Aggregate Determination by Permeation Technique
Phennapha Saokham and Thorsteinn Loftsson
Abstract
Permeation technique is used to study molecular aggregation in aqueous solutions including formation of
cyclodextrin guest/host aggregates. Since only guest molecules, host molecules and guest/host aggregates that are smaller than the pore size of a given semipermeable membrane are able to permeate through
the membrane, negative deviation of permeation profiles indicates formation of guest/host aggregates or
self-aggregates. This chapter describes how the method is used to detect formation of nano-sized aggregates and to determine the critical aggregation concentration (cac) from permeation profiles of a guest
molecule.
Key words Inclusion complexes, Critical aggregation concentration (cac), Permeation, Aggregates
1 Introduction
Clear aqueous solutions can contain molecular aggregates with
diameter below the wavelength of visible light. Frequently these
aggregates and clusters are transient; that is, they are constantly
being formed and dissembled [1]. Thus, it can be difficult to detect
them through conventional methods like dynamic light scattering
(DLS). Molecular membrane permeation is a passive diffusion process as described by Fick’s law [2]. Herein, we demonstrate how
the permeation technique through semipermeable membranes is
used to study the formation of transient guest/host aggregates
(e.g., drug/cyclodextrin complex aggregates) and clusters (i.e.,
loosely connected molecular structures). This method is based on
permeation of aggregating molecules through semipermeable
membranes of different molecular weight cutoffs (MWCOs) [3–
9]. Donor solutions (i.e., the test solutions) containing various
concentrations of, for example, guest/host aggregates or selfaggregates are placed in the donor chamber of Franz diffusion cells
(Fig. 1) [3–8] or miniature dialysis devices such as microequilibrium dialysis device (Fig. 2) [10] or cuplike MINI dialysis