Haemocompatibility and ion exchange capability of nanocellulose polypyrrole membranes intended for blood purification

Composites of nanocellulose and the conductive polymer polypyrrole (PPy) are presented as candidates for a new generation of haemodialysis membranes. The composites may combine active ion exchange with passive ultrafiltration, and the large surface area (about 80 m2 g−1) could potentially provide compact dialysers. Herein, the haemocompatibility of the novel membranes and the feasibility of effectively removing small uraemic toxins by potential-controlled ion exchange were studied. The thrombogenic properties of the composites were improved by applying a stable heparin coating. In terms of platelet adhesion and thrombin generation, the composites were comparable with haemocompatible polymer polysulphone, and regarding complement activation, the composites were more biocompatible than commercially available membranes. It was possible to extract phosphate and oxalate ions from solutions with physiological pH and the same tonicity as that of the blood. The exchange capacity of the materials was found to be 600 ± 26 and 706 ± 31 μmol g−1 in a 0.1 M solution (pH 7.4) and in an isotonic solution of phosphate, respectively. The corresponding values with oxalate were 523 ± 5 in a 0.1 M solution (pH 7.4) and 610 ± 1 μmol g−1 in an isotonic solution. The heparinized PPy–cellulose composite is consequently a promising haemodialysis material, with respect to both potential-controlled extraction of small uraemic toxins and haemocompatibility

High-Capacity Conductive Nanocellulose Paper Sheets for Electrochemically Controlled Extraction of DNA Oligomers

Highly porous polypyrrole (PPy)-nanocellulose paper sheets have been evaluated as inexpensive and disposable electrochemically controlled three-dimensional solid phase extraction materials. The composites, which had a total anion exchange capacity of about 1.1 mol kg−1, were used for extraction and subsequent release of negatively charged fluorophore tagged DNA oligomers via galvanostatic oxidation and reduction of a 30–50 nm conformal PPy layer on the cellulose substrate. The ion exchange capacity, which was, at least, two orders of magnitude higher than those previously reached in electrochemically controlled extraction, originated from the high surface area (i.e. 80 m2 g−1) of the porous composites and the thin PPy layer which ensured excellent access to the ion exchange material. This enabled the extractions to be carried out faster and with better control of the PPy charge than with previously employed approaches. Experiments in equimolar mixtures of (dT)6, (dT)20, and (dT)40 DNA oligomers showed that all oligomers could be extracted, and that the smallest oligomer was preferentially released with an efficiency of up to 40% during the reduction of the PPy layer. These results indicate that the present material is very promising for the development of inexpensive and efficient electrochemically controlled ion-exchange membranes for batch-wise extraction of biomolecules

Engineering of Native Cellulose Structure for Pharmaceutical Applications : Influence of Cellulose Crystallinity Index, Surface Area and Pore Volume on Sorption Phenomena

Cellulose powders from various sources were manufactured and characterized to investigate the influence of their crystallinity index, surface area, and pore volume on sorption phenomena and the relevant pharmaceutical functionality. The influence of the cellulose crystallinity index on moisture sorption was important at low and intermediate relative humidities. At high relative humidities, properties such as surface area and pore volume took precedence in governing the moisture sorption process. The theory of physical adsorption of gases onto fractal surfaces was useful for understanding the distribution of water in cellulose and the inner nanoscale structure of cellulose particles. It was found that, as a consequence of swelling, moisture induces a fractal nanopore network in cellulose powders that have a low or intermediate degree of crystallinity. On the other hand, no swelling occurs in highly crystalline cellulose powders and moisture sorption is restricted to the walls of the open pores. No correlation was found between the cellulose crystallinity index and the incorporation and release of nicotine in cellulose mixtures. By loading nicotine in highly porous matrices of the Cladophora sp. algae cellulose, higher stability against oxidative degradation, higher loading capacity, and more steady release into an air-stream was achieved than when commercially available microcrystalline cellulose was loaded. It was also shown that, by manipulating the structure of cellulose, the undesired hydrolysis of acetylsalicylic acid in mixtures with cellulose can be avoided. It was suggested that a broad hysteresis loop between the moisture adsorption and desorption curves of isotherms at low relative humidities could be indicative of an improved compatibility between acetylsalicylic acid and cellulose. In all, this thesis demonstrates how the pharmaceutical functionality of microcrystalline cellulose can be improved via engineering of the structure of native cellulose powders

Dissolution Behavior of Flufenamic Acid in Heated Mixtures with Nanocellulose

Flufenamic acid (FFA) is a problem drug that has up to eight different polymorphs and shows poor solubility. Variability in bioavailability has been reported in the past resulting in limited use of FFA in the oral solid dosage form. The goal of this article was to investigate the polymorphism and amorphization behavior of FFA in non-heated and heated mixtures with high surface area nanocellulose, i.e., Cladophora cellulose (CLAD). As a benchmark, low surface area microcrystalline cellulose (MCC) was used. The solid-state properties of mixtures were characterized with X-ray diffraction, Fourier-transform infrared spectroscopy, and differential scanning calorimetry. The dissolution behavior of mixtures was studied in three biorelevant media, i.e., fasted state simulated gastric fluid, fasted state simulated intestinal fluid, and fed state simulated intestinal fluid. Additional thermal analysis and dissolution tests were carried out following 4 months of storage at 75% RH and room temperature. Heated mixtures of FFA with CLAD resulted in complete amorphization of the drug, whereas that with MCC produced a mixture of up to four different polymorphs. The amorphous FFA mixture with CLAD exhibited rapid and invariable fasted/fed state dissolution in simulated intestinal fluids, whereas that of MCC mixtures was highly dependent on the biorelevant medium. The storage of the heated FFA-CLAD mixture did not result in recrystallization or changes in dissolution profile, whereas heated FFA-MCC mixture showed polymorphic changes. The straightforward dry powder formulation strategy presented here bears great promise for reformulating a number of problem drugs to enhance their dissolution properties and reduce the fasted/fed state variability

Immediate-Release Nifedipine Binary Dry Powder Mixtures with Nanocellulose Featuring Enhanced Solubility and Dissolution Rate

Nifedipine (NIF) is a 1,4-dihydropyridine-based calcium channel blocker with poor solubility, whose bioavailability is highly dependent on the type of formulation. Dry powder mixtures of 20% w/w NIF with microcrystalline cellulose (MCC) and its high surface area nanocellulose analogue, which is namely Cladophora (CLAD) cellulose, were produced by heating at the melting temperature of the drug for 1 h. Non-heated samples were used as a reference. The solid-state properties of the mixtures were characterized by scanning electron microscopy, differential scanning calorimetry and X-ray diffraction. The drug release was studied in biorelevant media, including simulated gastric fluid (SGF), fasted-state simulated intestinal fluid (FaSIF) and fed-state simulated intestinal fluid (FeSIF). An enhanced apparent solubility and faster dissolution rate of NIF were observed in the heated mixture of NIF with CLAD-H in all tested biorelevant media (i.e., SGF, FaSIF and FeSIF), which was due to NIF amorphization in the high surface area nanocellulose powder. Ordinary MCC, which is essentially non-porous, did not produce an enhancement of a similar magnitude. The results of the study suggest that dry powder formulation using high surface area nanocellulose is a facile new strategy for formulating calcium channel blocker drugs, which could potentially be a viable alternative to currently used soft gel liquid capsules

Surface transition on ice induced by the formation of a grain boundary

Interfaces between individual ice crystals, usually referred to as grain boundaries, play an important part in many processes in nature. Grain boundary properties are, for example, governing the sintering processes in snow and ice which transform a snowpack into a glacier. In the case of snow sintering, it has been assumed that there are no variations in surface roughness and surface melting, when considering the ice-air interface of an individual crystal. In contrast to that assumption, the present work suggests that there is an increased probability of molecular surface disorder in the vicinity of a grain boundary. The conclusion is based on the first detailed visualization of the formation of an ice grain boundary. The visualization is enabled by studying ice crystals growing into contact, at temperatures between −20°C and −15°C and pressures of 1–2 Torr, using Environmental Scanning Electron Microscopy. It is observed that the formation of a grain boundary induces a surface transition on the facets in contact. The transition does not propagate across facet edges. The surface transition is interpreted as the spreading of crystal dislocations away from the grain boundary. The observation constitutes a qualitatively new finding, and can potentially increase the understanding of specific processes in nature where ice grain boundaries are involved