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usc This paper reports the oxidation of inulin using varying ratios of sodium periodate and the characterization of the inulin polyaldehyde. The physicochemical properties of the inulin polyaldehyde (oxidized inulin) were characterized using different techniques including 1D NMR spectroscopy, 13C Nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), differential scanning calorimetric (DSC), ultraviolet-visible spectroscopy (UV), and scanning electron microscopy (SEM). The aldehyde peak was not very visible in the FTIR, because the aldehyde functional group exists in a masked form (hemiacetal). The thermal stability of the oxidized inulin decreased with the increasing oxidation degree. The smooth spherical shape of raw inulin was destructed due to the oxidation, as confirmed by the SEM result. The 1HNMR results show some new peaks from 4.8 to 5.0 as well as around 5.63 ppm. However, no aldehyde peak was found around 9.7 ppm. This can be attributed to the hemiacetal. The reaction of oxidized inulin with tert-butyl carbazate produced a carbazone conjugate. There was clear evidence of decreased peak intensity for the proton belonging to the hemiacetal group. This clearly shows that not all of the hemiacetal group can be reverted by carbazate. In conclusion, this work provides vital information as regards changes in the physicochemical properties of the oxidized inulin, which has direct implications when considering the further utilization of this biomaterial. Refereed/Peer-reviewed

The use of particles for monocyte-mediated delivery could be a more efficient strategy and approach to achieve intracellular targeting and delivery of antitubercular drugs to host macrophages. In this study, the potential of inulin microparticles to serve as a drug vehicle in the treatment of chronic tuberculosis using a monocytes-mediated drug targeting approach was evaluated. Isoniazid (INH) was conjugated to inulin via hydrazone linkage in order to obtain a pH-sensitive inulin-INH conjugate. The conjugate was then characterized using proton nuclear magnetic resonance (1HNMR), Fourier transform infrared spectroscopy (FTIR) as well as in vitro, cellular uptake and intracellular Mycobacterium tuberculosis (Mtb) antibacterial efficacy. The acid-labile hydrazone linkage conferred pH sensitivity to the inulin-INH conjugate with ~95, 77 and 65% of the drug released after 5 h at pH 4.5, 5.2, and 6.0 respectively. Cellular uptake studies confirm that RAW 264.7 monocytic cells efficiently internalized the inulin conjugates into endocytic compartments through endocytosis. The intracellular efficacy studies demonstrate that the inulin conjugates possess a dose-dependent targeting effect against Mtb-infected monocytes. This was through efficient internalization and cleavage of the hydrazone bond by the acidic environment of the lysosome, which subsequently released the isoniazid intracellularly to the Mtb reservoir. These results clearly suggest that inulin conjugates can serve as a pH-sensitive intracellular drug delivery system for TB treatment Refereed/Peer-reviewed

Inulin-based hydrogels are useful carriers for the delivery of drugs in the colon-targeted system and in other biomedical applications. In this project, inulin hydrogels were fabricated by crosslinking oxidized inulin with adipic acid dihydrazide (AAD) without the use of a catalyst or initiator. The physicochemical properties of the obtained hydrogels were further characterized using different techniques, such as swelling experiments, in vitro drug release, degradation, and biocompatibility tests. The cross linking was confirmed with Fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), and differential scanning calorimetry (DSC). In vitro releases of 5-fluorouracil (5FU) from the various inulin hydrogels was enhanced in acidic conditions (pH 5) compared with physiological pH (pH 7.4). In addition, blank gels did not show any appreciable cytotoxicity, whereas 5FU-loaded hydrogels demonstrated efficacy against HCT116 colon cancer cells, which further confirms the potential use of these delivery platforms for direct targeting of 5-FU to the colon Refereed/Peer-reviewed

The propensity of monocytes to migrate into sites of mycobacterium tuberculosis (TB) infection and then become infected themselves makes them potential targets for delivery of drugs intracellularly to the tubercle bacilli reservoir. Conventional TB drugs are less effective because of poor intracellular delivery to this bacterial sanctuary. This study highlights the potential of using semicrystalline delta inulin particles that are readily internalised by monocytes for a monocyte-based drug delivery system. Pyrazinoic acid was successfully attached covalently to the delta inulin particles via a labile linker. The formation of new conjugate and amide bond was confirmed using zeta potential, Proton Nuclear Magnetic Resonance (1HNMR) and Fourier transform infrared spectroscopy (FTIR). Scanning electron microscopy (SEM) confirmed that no significant change in size after conjugation which is an important parameter for monocyte targeting. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) were used to establish the change in thermal properties. The analysis of in-vitro release demonstrated pH-triggered drug cleavage off the delta inulin particles that followed a first-order kinetic process. The efficient targeting ability of the conjugate for RAW 264.7 monocytic cells was supported by cellular uptake studies. Overall, our finding confirmed that semicrystalline delta inulin particles (MPI) can be modified covalently with drugs and such conjugates allow intracellular drug delivery and uptake into monocytes, making this system potentially useful for the treatment of TB. Refereed/Peer-reviewed

Smart hydrogels with pH and enzyme triggered release suitable for colon specific drug delivery were prepared by crosslinking inulin with pyromellitic dianhydride (PMDA) in a simple one pot synthesis. Back titration, Fourier transform infrared spectroscopy (FTIR) and ultraviolet spectrophotometry (UV) demonstrated that the hydrogel crosslinking reaction resulted in ester linkages and carboxylic acid groups and that the amount of the crosslinker in the hydrogel increased with increasing PMDA concentration in the crosslinking reaction. Thermal analysis and scanning electron microscopy (SEM) confirmed the chemical change by illustrating the hydrogels changed thermal properties and appearance compared to inulin. This hydrogel showed excellent swelling in water and the degree of swelling was inversely proportional to the cross-linking density, as determined using Flory-Rehner theory. Due to the presence of the carboxylic acid groups in the structure, the swelling was pH dependent, with significantly reduced swelling as acidity decreased from pH 7.4 to pH 1.2. Refereed/Peer-reviewed

Delta inulin, also known as microparticulate inulin (MPI), was modified by covalently attaching doxorubicin to its nanostructured surface for use as a targeted drug delivery vehicle. MPI is readily endocytosed by monocytes, macrophages, and dendritic cells and in this study, we sought to utilize this property to develop a system to target anti-cancer drugs to lymphoid organs. We investigated, therefore, whether MPI could be used as a vehicle to deliver doxorubicin selectively, thereby reducing the toxicity of this antibiotic anthracycline drug. Doxorubicin was covalently attached to the surface of MPI using an acid&ndash, labile linkage to enable pH-controlled release. The MPI-doxorubicin conjugate was characterized using FTIR and SEM, confirming covalent attachment and indicating doxorubicin coupling had no obvious impact on the physical nanostructure, integrity, and cellular uptake of the MPI particles. To simulate the stability of the MPI-doxorubicin in vivo, it was stored in artificial lysosomal fluid (ALF, pH 4.5). Although the MPI-doxorubicin particles were still visible after 165 days in ALF, 53% of glycosidic bonds in the inulin particles were hydrolyzed within 12 days in ALF, reflected by the release of free glucose into solution. By contrast, the fructosidic bonds were much more stable. Drug release studies of the MPI-doxorubicin in vitro, demonstrated a successful pH-dependent controlled release effect. Confocal laser scanning microscopy studies and flow cytometric analysis confirmed that when incubated with live cells, MPI-doxorubicin was efficiently internalized by immune cells. An assay of cell metabolic activity demonstrated that the MPI carrier alone had no toxic effects on RAW 264.7 murine monocyte/macrophage-like cells, but exhibited anti-cancer effects against HCT116 human colon cancer cells. MPI-doxorubicin had a greater anti-cancer cell effect than free doxorubicin, particularly when at lower concentrations, suggesting a drug-sparing effect. This study establishes that MPI can be successfully modified with doxorubicin for chemotherapeutic drug delivery.

This review investigates the significant role polysaccharide particles play in functional drug delivery. The importance of these systems is due to the wide variety of polysaccharides and their natural source meaning that they can provide biocompatible and biodegradable systems with a range of both biological and chemical functionality valuable for drug delivery. This functionality includes protection and presentation of working therapeutics through avoidance of the reticuloendothelial system, stabilization of biomacromolecules and increasing the bioavailability of incorporated small molecule drugs. Transport of the therapeutic is also key to the utility of polysaccharide particles, moving drugs from the site of administration through mucosal binding and transport and using chemistry, size and receptor mediated drug targeting to specific tissues. This review also scrutinizes the methods of synthesizing and constructing functional polysaccharide particle drug delivery systems that maintain and extend the functionality of the natural polysaccharides. Refereed/Peer-reviewed

Filtration membrane technologies are used extensively in dairy processing and due to the high quantities of both organic and inorganic foulant, membrane fouling is a significant problem in the industry. To address this issue, a polyzwitterionic antifouling coating was applied to polyethersulfone ultrafiltration membranes for reduction of biofouling in skim milk filtration. The novel polyzwitterion was synthesised from a branched polyethyleneimine-based macroinitiator to allow multidentate binding to polydopamine coated membranes. Attachment of polyzwitterion to the polydopamine was confirmed using FTIR-ATR and XPS and the coating proved effective in increasing the wettability and smoothness of the membrane surface as well as reducing its charge. The reduced strength of binding between proteins and the membrane of the coated membrane compared to the control was demonstrated with its positive influence on fouling coefficient and recovery of the membranes while retaining skim milk flux and the rejection characteristics of the control membrane. The improved filtration characteristics of the coated membranes were generally retained through multiple cleaning cycles, though there was evidence of oxidative degradation after sanitation. Refereed/Peer-reviewed

Polymeric smart materials have a significant role in providing tuneable and sustained release of both hydrophilic and hydrophobic drugs. This chapter is a review on the use of swelling controlled drug delivery systems in the pharmaceutical industry, examining the evolution of swellable polymeric materials into effective delivery systems for therapeutic agents. Within the sub-classes of swelling devices, swellable matrices and superdisintegrants, the discussion of swellable controlled drug delivery devices and systems focus on their structures, properties, and swelling mechanisms. Major factors influencing the manner of drug release will also be investigated, as will mathematical models used to predict drug release characteristics. In the final section, the potential drawbacks of swellable controlled drug delivery systems will be discussed.

A practical fabrication technique is presented to tackle the trade-off between the water flux and salt rejection of thin film composite (TFC) reverse osmosis (RO) membranes through controlled creation of a thinner active selective polyamide (PA) layer. The new thin film nano-composite (TFNC) RO membranes were synthesized with multifunctional poly tannic acid-functionalized graphene oxide nanosheets (pTA-f-GO) embedded in its PA thin active layer, which is produced through interfacial polymerization. The incorporation of pTA-f-GOL into the fabricated TFNC membranes resulted in a thinner PA layer with lower roughness and higher hydrophilicity compared to pristine membrane. These properties enhanced both the membrane water flux (improved by 40%) and salt rejection (increased by 8%) of the TFNC membrane. Furthermore, the incorporation of biocidal pTA-f-GO nanosheets into the PA active layer contributed to improving the antibacterial properties by 80%, compared to pristine membrane. The fabrication of the pTA-f-GO nanosheets embedded in the PA layer presented in this study is a very practical, scalable and generic process that can potentially be applied in different types of separation membranes resulting in less energy consumption, increased cost-efficiency and improved performance.

Polydopamine and related polycatecholamines can be easily deposited onto almost any surface from mild, aqueous solution. This results in durable, nanoscale coatings that exhibit high biocompatibility and have useful chemical and electronic properties. Additionally, these materials can be readily chemically and physically modified, and consequently, they are used extensively for surface modification. This review investigates the formation and modification of polycatecholamines; how they adhere to surfaces; and the chemical, physical, and electronic properties of the resultant materials. There is also an exploration of the extraordinary array of applications in which these fascinating materials are employed. Refereed/Peer-reviewed

Graphene oxide (GO) nanosheets have anti-bacterial properties that have been exploited as a biocidal agent used on desalination membrane surfaces in recent research. Nonetheless, improved strategies for efficient and stable attachment of GO nanosheets onto the membrane surface are still required for this idea to be commercially viable. To address this challenge, we adopted a novel, single-step surface modification approach using tannic acid cross-linked with polyethylene imine as a versatile platform to immobilize GO nanosheets to the surface of polyamide (PA) thin film composite (TFC) forward osmosis (FO) membranes. An experimental design based on Taguchi’s statistical method was applied to optimize the FO processing conditions in terms of water and reverse solute fluxes. Modified membranes were analyzed using water contact angle (WCA), adenosine triphosphate (ATP) bioluminescence, total organic carbon (TOC), Fourier transform infrared spectroscopy (FTIR), zeta potential, X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM) and atomic force microscopy (AFM). These results show that membranes were modified with a nanoscale (< 10 nm), smooth, hydrophilic coating that, compared to pristine membranes, improved filtration and significantly mitigated biofouling by 33% due to its extraordinary, synergistic antibacterial properties (99.9%). Refereed/Peer-reviewed

This study combined physical data from synchrotron SAXS, FTIR and microscopy with in-silico molecular structure predictions and mathematical modeling to examine inulin adjuvant particle formation and structure. The results show that inulin polymer chains adopt swollen random coil in solution. As precipitation occurs from solution, interactions between the glucose end group of one chain and a fructose group of an adjacent chain help drive organized assembly, initially forming inulin ribbons with helical organization of the chains orthogonal to the long-axis of the ribbon. Subsequent aggregation of the ribbons results in the layered semicrystalline particles previously shown to act as potent vaccine adjuvants. γ-Inulin adjuvant particles consist of crystalline layers 8.5 nm thick comprising helically organized inulin chains orthogonal to the plane of the layer. These crystalline layers alternate with amorphous layers 2.4 nm thick, to give overall particle crystallinity of 78%. Refereed/Peer-reviewed