Solution-Spinning of a Collection of Micro- and Nanocarrier-Functionalized Polysaccharide Fibers

Continuous polysaccharide fibers and nonwovens—based on cellulose, hydroxypropyl cellulose, chitosan, or alginate—containing biopolymeric microcapsules (MC) or mesoporous silica nanoparticles (MSN) are prepared using a wet-spinning or solution blowing technique. The MCs are homogeneously distributed in the fiber matrices whereas the MSNs form discrete micron-sized aggregates as demonstrated using scanning electron-, fluorescence-, and confocal microscopy. By encapsulating the model compound pyrene, it is shown that 95% of the substance remains in the fiber during the formation process as compared to only 7% for the nonencapsulated substance. The material comprising the MC has a strong impact on the release behavior of the encapsulated pyrene as investigated using methanol extraction. MCs based on poly(l-lactic acid) prove to be practically impermeable with no pyrene released in contrast to MCs based on poly(lactic-co-glycolic acid) which allow for diffusion of pyrene through the MC and fiber as visualized using fluorescence microscopy

Enhancing the cellular uptake and antibacterial activity of rifampicin through encapsulation in mesoporous silica nanoparticles

An urgent demand exists for the development of novel delivery systems that efficiently transport antibacterial agents across cellular membranes for the eradication of intracellular pathogens. In this study, the clinically relevant poorly water-soluble antibiotic, rifampicin, was confined within mesoporous silica nanoparticles (MSN) to investigate their ability to serve as an efficacious nanocarrier system against small colony variants of Staphylococcus aureus (SCV S. aureus) hosted within Caco-2 cells. The surface chemistry and particle size of MSN were varied through modifications during synthesis, where 40 nm particles with high silanol group densities promoted enhanced cellular uptake. Extensive biophysical analysis was performed, using quartz crystal microbalance with dissipation (QCM-D) and total internal reflection fluorescence (TIRF) microscopy, to elucidate the mechanism of MSN adsorption onto semi-native supported lipid bilayers (snSLB) and, thus, uncover potential cellular uptake mechanisms of MSN into Caco-2 cells. Such studies revealed that MSN with reduced silanol group densities were prone to greater particle aggregation on snSLB, which was expected to restrict endocytosis. MSN adsorption and uptake into Caco-2 cells correlated well with antibacterial efficacy against SCV S. aureus, with 40 nm hydrophilic particles triggering a ~2.5-log greater reduction in colony forming units, compared to the pure rifampicin. Thus, this study provides evidence for the potential to design silica nanocarrier systems with controlled surface chemistries that can be used to re-sensitise intracellular bacteria to antibiotics by delivering them to the site of infection

Formation of Supported Lipid Bilayers Derived from Vesicles of Various Compositional Complexity on Conducting Polymer/Silica Substrates

Supported lipid bilayers (SLBs) serve important roles as minimalistic models of cellular membranes in multiple diagnostic and pharmaceutical applications as well as in the strive to gain fundamental insights about their complex biological function. To further expand the utility of SLBs, there is a need to go beyond simple lipid compositions to thereby better mimic the complexity of native cell membranes, while simultaneously retaining their compatibility with a versatile range of analytical platforms. To meet this demand, we have in this work explored SLB formation on PEDOT:PSS/silica nanoparticle composite films and mesoporous silica films, both capable of transporting ions to an underlying conducting PEDOT:PSS film. The SLB formation process was evaluated by using the quartz crystal microbalance with dissipation (QCM-D) monitoring, total internal reflection fluorescence (TIRF) microscopy, and fluorescence recovery after photobleaching (FRAP) for membranes made of pure synthetic lipids with or without the reconstituted membrane protein β-secretase 1 (BACE1) as well as cell-derived native lipid vesicles containing overexpressed BACE1. The mesoporous silica thin film was superior to the PEDOT:PSS/silica nanoparticle composite, providing successful formation of bilayers with high lateral mobility and low defect density even for the most complex native cell membranes.Funding: Swedish Foundation for Strategic Research (SSF)Swedish Foundation for Strategic Research [RMA11-0104]; Knut and Alice Wallenberg FoundationKnut &amp; Alice Wallenberg Foundation; SSFSwedish Foundation for Strategic Research [RIT15-0119]; Onnesjo Foundation</p