RESUMEN
We examine the influence of surface charge on the percolation, gel-point and phase behavior of cellulose nanocrystal (CNC) suspensions in relation to their nonlinear rheological material response. Desulfation decreases CNC surface charge density which leads to an increase in attractive forces between CNCs. Therefore, by considering sulfated and desulfated CNC suspensions, we are comparing CNC systems that differ in their percolation and gel-point concentrations relative to their phase transition concentrations. The results show that independently of whether the gel-point (linear viscoelasticity, LVE) occurs at the biphasic - liquid crystalline transition (sulfated CNC) or at the isotropic - quasi-biphasic transition (desulfated CNC), the nonlinear behavior appears to mark the existence of a weakly percolated network at lower concentrations. Above this percolation threshold, nonlinear material parameters are sensitive to the phase and gelation behavior as determined in static (phase) and LVE conditions (gel-point). However, the change in material response in nonlinear conditions can occur at higher concentrations than identified through polarized optical microscopy, suggesting that the nonlinear deformations could distort the suspensions microstructure such that for example a liquid crystalline phase (static) suspension could show microstructural dynamics similar to a biphasic system.
RESUMEN
The need for long-term treatments of chronic diseases has motivated the widespread development of long-acting parenteral formulations (LAPFs) with the aim of improving drug pharmacokinetics and therapeutic efficacy. LAPFs have been proven to extend the half-life of therapeutics, as well as to improve patient adherence; consequently, this enhances the outcome of therapy positively. Over past decades, considerable progress has been made in designing effective LAPFs in both preclinical and clinical settings. Here we review the latest advances of LAPFs in preclinical and clinical stages, focusing on the strategies and underlying mechanisms for achieving long acting. Existing strategies are classified into manipulation of in vivo clearance and manipulation of drug release from delivery systems, respectively. And the current challenges and prospects of each strategy are discussed. In addition, we also briefly discuss the design principles of LAPFs and provide future perspectives of the rational design of more effective LAPFs for their further clinical translation.
RESUMEN
HYPOTHESIS: In solvent casting, colloidal nanocrystal self-assembly patterns are controlled by a mix of cohesive and repulsive interactions that promote destabilization-induced self-assembly (DISA) or evaporation-induced self-assembly (EISA). Tuning the strength and nature of the stabilization mechanisms may allow repulsive interactions to govern self-assembly during the casting of colloidal cellulose nanocrystal (CNC) suspensions. EXPERIMENTS: We propose a tool to classify the level of electrostatic and solvation-induced stabilizations based on two solvent parameters only: dielectric constant, ε, and chemical affinity for CNCs, in terms of Hansen Solubility Parameters, Ra. These criteria are applied to study CNC self-assembly in solvent casting experiments in various media and binary mixtures. FINDINGS: In solvent casting of suspensions stabilized through a combination of electrostatic and solvation effects, the primarily governing mechanism is EISA, which leads to the formation of chiral nematic domains and optically active thin films. In electrostatically-stabilized suspensions, EISA and DISA are in competition and casting may yield anything from a continuous film to a powder. In other suspensions, DISA prevails and evaporation yields a powder of CNC agglomerates. By classifying media according to their stabilization mechanisms, this work establishes that the behavior of CNC suspensions in solvent casting may be predicted from solvent parameters only.