Polymer micelles as drug carriers

Block copolymer micelles are composed of polymer chains with sequences of hydrophilic and hydrophobic blocks. In a dilute aqueous solution, they form spherical or cylindrical nano-objects comprised of several chains with a hydrophobic core and extended hydrophilic corona. Lipophilic drugs can be dissolved in the core of these micelles, while the corona will assure solubility of this nano-container in aqueous media. In addition, if the corona is composed of a block which does not induce the immune reaction (for example PEO) the interior of the micelle will be invisible to the immune system. Such systems are extensively studied experimentally.

The questions that can be answered within the SCMFT method include: the critical micellar concentration (CMC) of the aggregates, the region of stability of micelles, the maximal load of drug as a function of a chain architecture, the equilibrium sizes and size distributions of micelles loaded with and without drug. Finally, we can predict the release rate of the active component, modifying the method in line with the Dynamic Density Functional Theory (DDFT) using the local variations of the SCMF free energy as the thermodynamic force causing the material flow. We are constantly looking for practical applications of our theory.

The architecture of the primary sequence of the block copolymer can be altered in order to achieve desired properties. For example, this is the case in the so-called scorpion-like surfactants, where the hydrophobic block is constructed from two stiff units composing a fixed angle. Such a structure allows for more space inside the core of the micelle to carry a lipophilic drug, thus increasing the load of drug per micelle.

The binding of the drug to the micelles described above is not very strong and the micelles normally dissociate when the bulk polymer concentration is below the CMC. This can be viewed as a disadvantage in some applications. If a stronger binding is required, the hydrophobic drug can be chemically attached to a hydrophilic linear polymer, as a side chain. Such a structure is known as a prodrug or polysoap. In an aqueous solution, the side chains containing drug form the core of the micelle, while the hydrophilic main chain forms the corona, mostly comprising loops. Such an aggregate is more stable than the simple micelle and does not release the drug until a chemical signal is given, for example, enzymatic degradation of the main chain at the target site. Since the only existing models are phenomenological models of polysoaps, the SCMFT method provides an important alternative that promises to give new and detailed information out of the reach for current capabilities.

One of the possibilities to form a stable aggregate is the complexation of charges of opposite sign. They are used for the delivery of charged chemicals as well as for specific binding to charged targets on the cell membranes. Usually the drug carrier designed for the delivery of a charged polymer is composed of a diblock copolymer: one block is charged and forms a complex with the drug while the other block is neutral and is devised to form the corona around the aggregate, aiming at shielding the complex from the solution.