Synthesis, Hydrophilicity and Micellization of Coil–Brush Polystyrene-b-(polyglycidol-g-polyglycidol) Copolymer—Comparison with Linear Polystyrene-b-Polyglycidol

In this paper, an original method of synthesis of coil–brush amphiphilic polystyrene-b-(polyglycidol-g-polyglycidol) (PS-b-(PGL-g-PGL)) block copolymers was developed. The hypothesis that their hydrophilicity and micellization can be controlled by polyglycidol blocks architecture was verified. The research enabled comparison of behavior in water of PS-b-PGL copolymers and block–brush copolymers PS-b-(PGL-g-PGL) with similar composition. The coil–brush copolymers were composed of PS-b-PGL linear core with average DPn of polystyrene 29 and 13 of polyglycidol blocks. The DPn of polyglycidol side blocks of coil–b–brush copolymers were 2, 7, and 11, respectively. The copolymers were characterized by 1H and 13C NMR, GPC, and FTIR methods. The hydrophilicity of films from the linear and coil–brush copolymers was determined by water contact angle measurements in static conditions. The behavior of coil–brush copolymers in water and their critical micellization concentration (CMC) were determined by UV-VIS using 1,6-diphenylhexa-1,3,5-trien (DPH) as marker and by DLS. The CMC values for brush copolymers were much higher than for linear species with similar PGL content. The results of the copolymer film wettability and the copolymer self-assembly studies were related to fraction of hydrophilic polyglycidol. The CMC for both types of polymers increased exponentially with increasing content of polyglycidol.

The role of critical micellization concentration in efficacy and toxicity of supramolecular polymers

The inception and development of supramolecular chemistry have provided a vast library of supramolecular structures and materials for improved practice of medicine. In the context of therapeutic delivery, while supramolecular nanostructures offer a wide variety of morphologies as drug carriers for optimized targeting and controlled release, concerns are often raised as to how their morphological stability and structural integrity impact their in vivo performance. After intravenous (i.v.) administration, the intrinsic reversible and dynamic feature of supramolecular assemblies may lead them to dissociate upon plasma dilution to a concentration below their critical micellization concentration (CMC). As such, CMC represents an important characteristic for supramolecular biomaterials design, but its pharmaceutical role remains elusive. Here, we report the design of a series of self-assembling prodrugs (SAPDs) that spontaneously associate in aqueous solution into supramolecular polymers (SPs) with varying CMCs. Two hydrophobic camptothecin (CPT) molecules were conjugated onto oligoethylene-glycol (OEG)-decorated segments with various OEG repeat numbers (2, 4, 6, 8). Our studies show that the lower the CMC, the lower the maximum tolerated dose (MTD) in rodents. When administrated at the same dosage of 10 mg/kg (CPT equivalent), SAPD 1, the one with the lowest CMC, shows the best efficacy in tumor suppression. These observations can be explained by the circulation and dissociation of SAPD SPs and the difference in molecular and supramolecular distribution between excretion and organ uptake. We believe these findings offer important insight into the role of supramolecular stability in determining their therapeutic index and in vivo efficacy.

Study of Micellar Behavior of Crown Ether and Tetraethylammonium Bromide in Aqueous Media

Conductivity measurements have been carried out to study the micellar behavior of tetraethylammonium bromide in presence of 15-crown-5 in aqueous media. The measurements were carried out at 298.15 K as a function of surfactant concentration with varying concentrations of crown ether. The influence of this association on the micellar parameters, such as the cmc (critical micellization concentration) and β (degree of counterion dissociation) have been analyzed. Thermodynamics of the systems were discussed in terms of the change in free energy of micellisation, ΔG0mby applying the charged pseudo-phase separation model. The trend shows that the micellization becomes less spontaneous in presence of crown ether. The influence of the presence of the inclusion complex on the micellization process of the surfactant has been studied.