Chitosan is a unique biopolymer in the respect that it is abundant, cationic, low-toxic, non-immunogenic and biodegradable. The relative occurrence of the two monomeric building units ...(N-acetyl-glucosamine and d-glucosamine) is crucial to whether chitosan is predominantly an ampholyte or predominantly a polyelectrolyte at acidic pH-values. The chemical composition is not only crucial to its surface activity properties, but also to whether and why chitosan can undergo a sol-gel transition. This review gives an overview of chitosan hydrogels and their biomedical applications, e.g., in tissue engineering and drug delivery, as well as the chitosan's surface activity and its role in emulsion formation, stabilization and destabilization. Previously unpublished original data where chitosan acts as an emulsifier and flocculant are presented and discussed, showing that highly-acetylated chitosans can act both as an emulsifier and as a flocculant.
The blood-brain barrier (BBB), composed of tightly organized endothelial cells, limits the availability of drugs to therapeutic targets in the central nervous system. The barrier is maintained by ...membrane bound efflux pumps efficiently transporting specific xenobiotics back into the blood. The efflux pump P-glycoprotein (P-gp), expressed at high levels in brain endothelial cells, has several drug substrates. Consequently, siRNA mediated silencing of the P-gp gene is one possible strategy how to improve the delivery of drugs to the brain. Herein, we investigated the potential of siRNA-chitosan nanoparticles in silencing P-gp in a BBB model. We show that the transfection of rat brain endothelial cells mediated effective knockdown of P-gp with subsequent decrease in P-gp substrate efflux. This resulted in increased cellular delivery and efficacy of the model drug doxorubicin.
In this report, the Commission provides updated guidance on radiological protection against radon exposure. The report has been developed considering the latest ICRP recommendations for the system of ...radiological protection, all available scientific knowledge about the risks of radon, and the experience gained by many organisations and countries in the control of radon exposure. The report describes the characteristics of radon exposure, covering sources and transfer mechanisms, the health risks associated with radon, and the challenges of managing radon exposure. The Commission recommends an integrated approach for controlling radon exposure, relying as far as possible on the management of buildings or locations in which radon exposure occurs, whatever the use of the building. This approach is based on the optimisation principle, and is graded reflecting the responsibilities of key stakeholders, notably in workplaces, and the intent of the national authorities to control radon exposure. The report also provides recommendations on managing radon exposure when workers’ exposures are considered as occupational, and the appropriate requirements of the Commission should be applied.
The interactions between DNA and chitosans varying in fractional content of acetylated units (FA), degree of polymerization (DP), and degree of ionization were investigated by several techniques, ...including an ethidium bromide (EtBr) fluorescence assay, gel retardation, atomic force microscopy, and dynamic and electrophoretic light scattering. The charge density of the chitosan and the number of charges per chain were found to be the dominating factors for the structure and stability of DNA-chitosan complexes. All high molecular weight chitosans condensed DNA into physically stable polyplexes; however, the properties of the complexes were strongly dependent on FA, and thereby the charge density of chitosan. By employing fully charged oligomers of constant charge density, it was shown that the complexation of DNA and stability of the polyplexes is governed by the number of cationic residues per chain. A minimum of 6-9 positive charges appeared necessary to provide interaction strength comparable to that of polycations. In contrast, further increase in the number of charges above 9 did not increase the apparent binding affinity as judged from the EtBr displacement assay. The chitosan oligomers exhibited a pH-dependent interaction with DNA, reflecting the number of ionized amino groups. The complexation of DNA and the stability of oligomer-based polyplexes became reduced above pH 7.4. Such pH-dependent dissociation of polyplexes around the physiological pH is highly relevant in gene delivery applications and might be one of the reasons for the high transfection activity of oligomer-based polyplexes observed.
Chitosan possesses many characteristics of an ideal gene delivery system. However, the transfection efficiency of conventional chitosans is generally found to be low. In this study, we investigated ...the self-branching of chitosans as a strategy to improve its gene transfer properties without compromising its safety profile. Self-branched (SB) and self-branched trisaccharide-substituted (SBTCO) chitosans with molecular weights of 11-71 kDa were synthesized, characterized, and compared with their linear counterparts with respect to transfection efficiency, cellular uptake, formulation stability, and cytotoxicity. Our studies show that in contrast with unmodified linear chitosans that were unable to transfect HeLa cells, self-branched chitosans mediated high transfection efficiencies. The most efficient chitosan, SBTCO30, yielded gene expression levels two and five times higher than those of Lipofectamine and Exgen, respectively, and was nontoxic to cells. Nanoparticles formed with SBTCO chitosans exhibited a higher colloidal stability of formulation, efficient internalization without excessive cell surface binding, and low cytotoxicity.
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