Liquid crystalline mesophase spacing as a quantitative predictor of release kinetics for co-loaded hydrophilic and hydrophobic payloads
TL;DR
Synchrotron SAXS establishes characteristic repeat spacing as a quantitative structural metric directly governing hydrophilic release kinetics, providing a rational design framework linking mesophase architecture to functional performance across a range of payload structures.
Abstract
Liquid crystalline mesophases exhibit structurally programmable internal architectures that enable co-loading of chemically orthogonal molecules within a single composite material. Realizing the potential of these materials for drug delivery requires a quantitative understanding of how tuning the composition affects internal mesophase architecture and consequently performance metrics such as payload release. Here, Flash NanoPrecipitation with hydrophobic ion pairing is used to prepare nanocarriers containing liquid crystalline mesophases co-encapsulating two compounds from widely different chemical classes: hydrophilic polymyxin B (logP –6) with one of four hydrophobic co-core materials (logP 7-11), achieving >75% encapsulation efficiency and up to 32% and 50% mass loadings for polymyxin and co-core. Synchrotron SAXS is used to quantify characteristic mesophase repeat spacing, which is found to be tunable as a function of composition. A strong correlation between d-spacing and polymyxin release rate is presented. Co-core chemistry and weight fraction jointly govern mesophase architecture, and repeat distance emerges as a structural metric linking these to the hydrophilic payload release kinetics. Mucus diffusivity and antibacterial efficacy are assessed as independent performance metrics, and results corroborate the release behavior. These findings establish a quantitative framework connecting material composition, mesophase architecture, and functional performance that can be applied toward rational co-formulation design. ToC Graphic Text Flash NanoPrecipitation yields liquid crystalline nanocarriers co-encapsulating with high efficiency payloads with widely distinct physicochemical properties. Synchrotron SAXS establishes characteristic repeat spacing as a quantitative structural metric directly governing hydrophilic release kinetics, providing a rational design framework linking mesophase architecture to functional performance across a range of payload structures.