Properties of Water Solutions of Synthetic Polyelectrolytes - Study Questions

Problem 1 (15 marks)

In the last decade, considerable attention has been paid to understand the properties of water solutions of the synthetic polyelectrolytes called x,y-ionenes (Figure 1). Ionene polymers can selectively bind to protoplasts that makes them potential cancer drugs. Besides this, the applicability of ionenes as non-vector gene delivery systems has been reported. Recently, polyelectrolyte multilayers built up using the ionenes as one of the polyelectrolytes have been proposed for controlled drug delivery. This has led the extensive study of ionene polymers.

Figure 1. The repeating unit of an x, y-ionene. In this case, x = y = 3 or 6. 

Q1. Does an x,y-ionene molecule generate a polycation or a polyanion? Weak or strong? (1 Marks)

The thermodynamics of the interaction of 3,3- and 6,6-ionene fluorides with sodium halide salts in water was studied by isothermal titration calorimetry. Table 1 below presents some thermodynamic parameters for the displacement of F^? by Cl^?, Br^?, and I^?, respectively, on mixing 3,3- and 6,6-ionene fluorides with sodium halide salts. Data apply to T₀ = 298 K.

Table 1. K – equilibrium constant, ?G – Gibbs free energy, ?H - enthalpy, ?S – entropy for the interaction of 3,3- and 6,6-ionene fluorides with sodium halide salts.

Q2. Calculate equilibrium constant and the Gibbs free energy for the interaction of 3,3- and 6,6-ionene fluorides with the sodium halide salts in water and add it into Table 1. (3 Marks)

Q3. Is the interaction of the 3,3- and 6,6-ionene fluorides with NaCl an exo- or endothermic process? Is it driven by entropy or enthalpy change? Explain your answer. (2 Marks)

Polyelectrolyte multilayers have been assembled from 3,3-ionene fluoride and poly-styrene sulfonate sodium salt.

Q4. Calculate Gibbs free energy for multilayer formation at the temperatures 20, 25, 30, 35, 40 and 45°C using the data from Table 2. (2 Marks)

Q5. Calculate the enthalpy and the entropy of multilayer formation. Insert the van't Hoff's plot below (as Figure 2). (4 Marks)

Table 2. K – equilibrium constant, ?G – Gibbs free energy for 3,3-ionene/PSS multilayer formation.

Q6. How will the addition of NaCl during the multilayer build up process influence the multilayer growth at 298 K? Make a conclusion based on the thermodynamic parameters. (3 Marks)

Polyelectrolyte multilayer capsules composed from alginic acid and chitosan have been templated on the surface of porous calcium carbonate spherical particles with the average diameters of 5 and 20 µm. Calcium carbonate cores were pre-loaded with the anticancer drug doxorubicin. Entrapment efficiency for doxorubicin is 85%. After the CaCO₃ core dissolution by the addition of 0.1 M citric acid, capsules templated on 5 µm particles were unstable and fused as shown in the scheme below. Capsules templated on 20 µm particles remain stable after core dissolution. In the first case (5 µm cores), 30% of pre-loaded doxorubicin has been released from the capsules and lost during the core dissolution and fusion. In the case of 20 µm CaCO₃ particles, 90% of doxorubicin has been kept inside the capsules.

The treatment of carcinoma requires 10 consecutive injections of 0.5 mg of doxorubicin per kg of a body mass. The patient has a weight of 80 kg.

Q1. Calculate the amount of doxorubicin needed to prepare (a) 5 and (b) 20 µm alginic acid/chitosan capsules for carcinoma treatment. (5 Marks)

Q2. Calculate how many capsules prepared on (a) 5 µm and (b) 20 µm cores will be injected for such a therapy (per 1 injection) if the initial concentration of doxorubicin (before core dissolution) in the capsule (of any type) is 20 mg mL^-1. (5 Marks) 

Capsule fusion: two capsules are fused (merged) and form a new spherical capsule retaining its internal volume.

A biomedical company has developed a novel anionic drug composed of a protein for the treatment of breast cancer. Based on the summary of polyelectrolyte carriers developed for encapsulation of different components (see the Table below) propose the best carrier for the intracellular drug delivery in vivo. Explain your answer.

CHI – chitosan, ALG – alginic acid, PLL – poly-L-lysine, HA – hyaluronic acid. 

Structural formula of natural polymers used.