Delivery of hydrophobic molecules and proteins has been an issue due to poor bioavailability following administration. Thus, micelle carrier systems are being investigated to improve drug solubility and stability. Due to problems with toxicity and immunogenicity, natural polysaccharides are being explored as substitutes for synthetic polymers in the development of new micelle systems. By grafting hydrophobic moieties to the polysaccharide backbone, self-assembled micelles can be readily formed in aqueous solution. Many polysaccharides also possess inherent bioactivity that can facilitate mucoadhesion, enhanced targeting of specific tissues, and a reduction in the inflammatory response. Furthermore, the hydrophilic nature of some polysaccharides can be exploited to enhance circulatory stability. This review will highlight the advantages of polysaccharide use in the development of drug delivery systems and will provide an overview of the polysaccharide-based micelles that have been developed to date.
Polyacrylamide-based conditioners have become an essential component of the geotextile tube dewatering processes. These conditioners act as flocculants, binding fine sediments through charge neutralisation and particle bridging, resulting in faster dewatering rates and greater retention of fine sediments. Recently, however, momentum has begun to shift towards the use of sustainable materials. Natural flocculants, such as starch and chitosan, are increasingly being tested as an attractive alternative to synthetic polymers. Researchers have identified a number of natural flocculants, polysaccharides and polysaccharide derivatives in particular, as candidates for dewatering applications. In this study, the dewatering performance of four soils (sand, silt, kaolin, and natural organic soil) was evaluated with synthetic and starch-based flocculants. Dewatering performance of five cationic starch-based polymers with charge densities ranging from 0.38 to 0.94 meq/g and molecular weights ranging from 5 × 104g/mol to 5 × 105g/mol were compared with five cationic acrylamide-based polymers with charge densities that ranged from 1 to 3.05 meq/g and molecular weights that ranged from 10 × 106to 20 × 106/mol. The cationic polyacrylamides and cationic starches were selected with a wide range of charge densities and molecular weights in order to study the effect of flocculant properties on the flocculation and dewatering performance of the used soils. The optimum dose of each flocculant was determined using the jar test. Additionally, pressure filtration tests were performed to determine the dewatering rates and filter cake properties. Test results showed that the flocculants' properties, especially charge density, have a significant effect on the optimum dose. The optimum doses of the cationic starch flocculants were two to four times higher than the cationic polyacrylamide polymers. Additionally, it was found that the cationic starches were more effective in minimising the turbidity of the natural organic soils than the cationic polyacrylamides. Finally, the cationic starches allowed for a 900% increase in dewatering rate in comparison with the soil samples that were tested without flocculants.
The transcription factor nuclear factor-kappa B (NF-κB) is highly involved in regulation of a number of cellular processes, including production of inflammatory mediators. Thus, this transcription factor plays a role in pathology of many diseases, including rheumatoid arthritis, an autoimmune disease hallmarked by an imbalance of pro and anti-inflammatory cytokines. Small nucleic acids with sequences that mimic the native binding site of NF-κB have been proposed as treatment options for RA; however due to low cellular penetration and a high degree of instability, clinical applications of these therapeutics have been limited. Here, we describe the use of N-trimethyl chitosan-polysialic acid (PSA-TMC) nanoparticles coated with decoy oligodeoxynucleotides (ODNs) specific to transcription factor NF-κB (PSA-TMC-ODN) as a method to enhance the stability of the nucleic acids and facilitate increased cellular penetration. In addition to decoy ODN, PSA-TMC nanoparticles were loaded with RA therapeutic methotrexate (MTX), to assess the anti-inflammatory efficacy of a combination therapy approach. Two different in vitro models, a cell line based model as well as a primary RA cell model were used to investigate anti-inflammatory activity. One way ANOVA followed by Holm-Sidak stepdown comparisons was used to determine statistical significance. In general, free ODN did not significantly affect secretion of pro-inflammatory cytokines interleukin-6 (IL-6) and interleukin-8, (IL-8) while free MTX had variable efficacy. However, PSA-TMC-ODN and PSA-TMC-ODN-MTX resulted in significant decreases in the inflammatory mediators IL-6 and IL-8 in both cell models. In addition, PSA-TMC exhibited sufficient cellular uptake, as observed through fluorescence microscopy. These results support our previous findings that PSA-TMC nanoparticles are an effective delivery vehicle for small nucleic acids, and effectively alter the pro-inflammatory state characteristic of RA.