ABSTRACT
Branched star polymers offer exciting opportunities in enhancing the efficacy of nanocarriers in delivering biologically active lipophilic agents. It is demonstrated that the star polymeric architecture can be leveraged to yield soft nanoparticles of vesicular morphology with precisely located stimuli-sensitive chemical entities. Amphiphilic stars of AB2 (A = PEG, B = PCL) composition with/without oxidative stress or reduction responsive units at the core junction of A and B arms, are constructed using synthetic articulation. Fisetin, a natural flavonoid with remarkable anti-inflammatory and antioxidant properties, but of limited clinical value due to its poor aqueous solubility, is physically encapsulated into miktoarm star-derived aqueous polymersomes. Polymersomes and fisetin are evaluated separately, and in combination, in human microglia (HMC3), to show if i) polymersomes are toxic; ii) fisetin reduces the abundance of reactive oxygen species (ROS); and iii) fisetin modulates the activation of ERK1/2. These signaling molecules and pathways are implicated in inflammatory processes and cell survival. Fisetin, both incorporated and nonincorporated into polymersomes, reduces ROS and ERK1/2 phosphorylation in lipopolysaccharide-treated human microglia, normalizing excessive oxidative stress and ERK-mediated signaling.
Subject(s)
Microglia , Stimuli Responsive Polymers , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Flavonols/pharmacology , Humans , Lipopolysaccharides/pharmacology , Microglia/metabolism , Polymers/chemistry , Reactive Oxygen Species/metabolismABSTRACT
Self-assembly of amphiphilic macromolecules has provided an advantageous platform to address significant issues in a variety of areas, including biology. Such soft nanoparticles with a hydrophobic core and hydrophilic corona, referred to as micelles, have been extensively investigated for delivering lipophilic therapeutics by physical encapsulation. Polymeric vesicles or polymersomes with similarities in morphology to liposomes continue to play an essential role in understanding the behavior of cell membranes and, in addition, have offered opportunities in designing smart nanoformulations. With the evolution in synthetic methodologies to macromolecular precursors, the construction of such assemblies can now be modulated to tailor their properties to match desired needs. This review brings into focus the current state-of-the-art in the design of polymersomes using amphiphilic miktoarm star polymers through a detailed analysis of the synthesis of miktoarm star polymers with tuned lengths of varied polymeric arms, their self-assembly, and applications in drug delivery.
Subject(s)
Drug Delivery Systems , Nanoparticles , Drug Delivery Systems/methods , Hydrophobic and Hydrophilic Interactions , Micelles , Polymers/chemistryABSTRACT
In this study, the solubility, density and viscosity of sorbitol as a sugar alcohol in the ([mmim](MeO)2PO2) ionic liquid (IL) were measured. The results indicated that sorbitol is highly soluble in this IL. The Flory-Huggins model with an average value for the χ parameter was successfully applied to predict the solubility of sorbitol in IL. The thermodynamic properties such as enthalpy, entropy and Gibbs free energy of dissolution were obtained using experimental solubility data, which demonstrated that the dissolution process is endothermic and non-spontaneous and includes an entropy increase. In addition, the apparent molar volume, apparent molar expansion and thermal expansion coefficient were calculated. The study of the rheological behavior revealed that the sorbitol/IL solution is Newtonian and the Arrhenius, Litovitz, Orrick-Erbar-Type and Vogel-Fulcher-Tamman models were used to correlate the viscosity data.
