ABSTRACT
Despite intense research, methods for controlling soft matter's spontaneous self-assembly into well-defined layers remain a significant challenge. We observed ion-induced structural discontinuities of phospholipid vesicles that can be exploited for controlled self-assembly of soft materials, using DOPC and NaCl as a model system. The observations were made for the 0.25 wt % lipid concentration. We used dynamic light scattering, zeta-potential measurement, cryo-electron microscopy, small-angle X-ray, and small-angle neutron scattering to understand the reason for the discontinuities. For salt concentrations below 8 mM, we observed a decrease in the liposome diameter with increased NaCl concentration. Above 8 mM, we measured a discontinuity; the radius increases within a very narrow salt concentration range within less than 0.1 mM and then decreases for values greater than 8 mM. At 75 mM, the radius becomes constant until it grows again at around 500 mM. Microscopy and scattering experiments show a transition from unilamellar to bilamellar at 8 mM and to trilamellar at 75 mM. At 500 mM, we found a heterogeneous liposome system with many different bilayer numbers. All the experimental observations indicate that declining solvent quality and increasing osmotic pressure direct lipids to expel preferentially to the inner compartment. Upon reaching a critical concentration, excess lipids can form a new bilayer. This spontaneous self-assembly process causes simultaneous shrinkage of the aqueous core and expansion of the vesicle. This approach opens an intriguing path for controlling the self-assembly of bioinspired colloids.
ABSTRACT
Despite decades of research, our understanding of the molecular interactions between drugs and polymers in drug-loaded polymer micelles does not extend much beyond concepts such as "like-dissolves-like" or hydrophilic/hydrophobic. However, polymer-drug compatibility strongly affects formulation properties and therefore the translation of a formulation into the clinics. Specific interactions such as hydrogen-bonding, π-π stacking, or coordination interactions can be utilized to increase drug loading. This is commonly based on trial and error and eventually leads to an optimized drug carrier. Unfortunately, due to the unique characteristics of each drug, the deduction of advanced general concepts remains challenging. Furthermore, the introduction of complex moieties or specifically modified polymers hampers systematic investigations regarding polymer-drug compatibility as well as clinical translation. In this study, we reduced the complexity to isolate the crucial factors determining drug loading. Therefore, the compatibility of 18 different amphiphilic polymers for five different hydrophobic drugs was determined empirically. Subsequently, the obtained specificities were compared to theoretical compatibilities derived from either the Flory-Huggins interaction parameters or the Hansen solubility parameters. In general, the Flory-Huggins interaction parameters were less suited to correctly estimate the experimental drug solubilization compared to the Hansen solubility parameters. The latter were able to correctly predict some trend regarding good and poor solubilizers, yet the overall predictive strength of Hansen solubility parameters is clearly unsatisfactory.
