Liesbeth Vervoort

Colonic drug targeting

Specific targeting of drugs to the colon is recognized to have several therapeutic advantages. Drugs which are destroyed by the stomach acid and/or metabolized by pancreatic enzymes are slightly affected in the colon, and sustained colonic release of drugs can be useful in the treatment of nocturnal asthma, angina and arthritis. Treatment of colonic diseases such as ulcerative colitis, colorectal cancer and Crohns disease is more effective with direct delivery of drugs to the affected area. Likewise, colonic delivery of vermicides and colonic diagnostic agents require smaller doses. This article is aimed at providing insight into the design considerations and evaluation of colonic drug delivery systems. For this purpose, the anatomy and physiology of the lower gastrointestinal tract are surveyed. Furthermore, the biopharmaceutical aspects are considered in relation to drug absorption in the colon and hence various approaches to colon-specific drug delivery are discussed.

Inulin hydrogels as carriers for colonic drug targeting: I. Synthesis and characterization of methacrylated inulin and hydrogel formation

AbstractPurpose. Vinyl groups were introduced in inulin chains in order to form hydrogels of this sugar polymer by free radical polymerization. Methods. Inulin was reacted with glycidyl methacrylate in N,N-dimethylformamide in the presence of 4-dimethylaminopyridine as catalyst. 1H and 13C NMR spectroscopy were used for the characterization of the obtained reaction product. Solid state 13C NMR spectroscopy revealed the conversion of the incorporated vinyl groups into covalent cross-links upon free radical polymerization of aqueous solutions of the derivatized inulin. Results. During reaction of inulin with glycidyl methacrylate, transesterification occurred, leading to the direct attachment of the methacryloyl group to inulin. Consequently, the obtained reaction product is methacrylated inulin. The extent of chemical modification of inulin could be tuned by varying the molar ratio of glycidyl methacrylate to inulin in the reaction mixture. Aqueous solutions of methacrylated inulin were converted into cross-linked hydrogels by free radical polymerization using ammonium persulphate and N,N,N′,N′-tetramethylethylenediamine as initiating system. Conclusions. Inulin hydrogels can be formed by free radical polymerization of aqueous solutions of methacrylated inulin.

In vitro degradation by colonic bacteria of inulinHP incorporated in Eudragit RS films

Inulin is a naturally-occurring gluco-fructan, which can resist hydrolysis and digestion in the upper gastro-intestinal tract. In the colon it is fermented by the colonic microflora. Therefore inulinHP (inulin with a high degree of polymerization) was formulated as a biodegradable colon-specific coating by suspending it in Eudragit RS films. The in vitro degradability of the prepared isolated films was studied by incubating them in a faecal degradation medium. Measurements of the pH of the degradation medium and determination of the permeability coefficients of the incubated films as a function of time, indicated that inulinHP was indeed degraded by the faecal bacteria, even when it was suspended in Eudragit RS films. Films with different amounts of incorporated inulinHP and with different plasticizers were evaluated. The isolated films could also withstand gastric and intestinal fluid.

Inulin hydrogels. I. Dynamic and equilibrium swelling properties

Inulin hydrogels were developed as potential new carriers for colonic drug targeting. This work describes the dynamic and equilibrium swelling properties of the prepared inulin hydrogels. The influence of various parameters on these properties were assessed, in particular the degree of substitution and feed concentration of methacrylated inulin and varying concentrations of the initiators of the polymerisation reaction. As these hydrogels were developed as colon-specific drug delivery systems, also the effect of pH, ionic strength and esterases were investigated. The results suggest that the rate of water transport into the inulin hydrogels is quite high (mean swelling time <1.2 h) and that the hydrogels exhibit anomalous dynamic swelling behaviour. The equilibrium swelling of the hydrogels is influenced by the degree of substitution and feed concentration of methacrylated inulin, by the initiator concentration, and by the ionic strength and an acidic pH of the swelling solvent. Esterase activity and pH values of the swelling solvent commonly encountered in the small intestine and the colon on the contrary do not affect equilibrium swelling. By means of differential scanning calorimetry, the glass transition temperature of dry methacrylated inulin hydrogel samples was determined. The mobility of the hydrogel chains seemed to be affected by both the degree of substitution and the feed concentration of methacrylated inulin.

Quality changes of pasteurised orange juice during storage: A kinetic study of specific parameters and their relation to colour instability.

In view of understanding colour instability of pasteurised orange juice during storage, to the best of our knowledge, this study reports for the first time in a systematic and quantitative way on a range of changes in specific quality parameters as a function of time and as well as temperature (20-42 °C). A zero-order (°Brix, fructose, glucose), a first-order (vitamin C), a second-order (sucrose) and a fractional conversion model (oxygen) were selected to model the evolution of the parameters between parentheses. Activation energies ranged from 22 to 136 kJ mol(-1), HMF formation being the most temperature sensitive. High correlations were found between sugars, ascorbic acid, their degradation products (furfural and HMF) and total colour difference (ΔE(∗)). Based on PLS regression, the importance of the quality parameters for colour degradation was ranked relatively among each other: the acid-catalysed degradation of sugars and ascorbic acid degradation reactions appeared to be important for browning development in pasteurised orange juice during ambient storage.

Headspace components that discriminate between thermal and high pressure high temperature treated green vegetables: Identification and linkage to possible process-induced chemical changes

For the first time in literature, this study compares the process-induced chemical reactions in three industrially relevant green vegetables: broccoli, green pepper and spinach treated with thermal and high pressure high temperature (HPHT) processing. Aiming for a fair comparison, the processing conditions were selected based on the principle of equivalence. A comprehensive integration of MS-based metabolic fingerprinting techniques, advanced data preprocessing and statistical data analysis has been implemented as untargeted/unbiased multiresponse screening tool to uncover changes in the volatile fraction. For all vegetables, thermal processing, compared to HPHT, seems to enhance Maillard and Strecker degradation reaction, triggering the formation of furanic compounds and Strecker aldehydes. In most cases, high pressure seems to accelerate (an)aerobic thermal degradation of unsaturated fatty acids leading to the formation of aliphatic aldehydes and ketones. In addition, both thermal and HPHT processing accelerated the formation of sulfur-containing compounds. This work demonstrated that the approach is effective in identifying and comparing different process-induced chemical changes, adding depth to our perspective in terms of studying a highly complex chemical changes occurring during food processing.

Inulin hydrogels. II. In vitro degradation study

Inulin hydrogels have been developed as potential new carriers for colonic drug targeting. Since site-specific drug release of this delivery system is based on its bacterial degradation in the colon, the enzymatic digestibility of the prepared inulin hydrogels was assessed by performing an in vitro study using an inulinase preparation derived from Aspergillus niger. The amount of fructose liberated from the inulin hydrogels by the action of inulinase was quantified using the anthrone method. The equilibrium swelling ratio as well as the mechanical strength of the hydrogels were studied before and after incubation in inulinase solutions. The data obtained by these different methods indicate that enzymatic digestion of the inulin hydrogels appeared to be enhanced by a prolonged degradation time, a higher inulinase concentration and a lower degree of substitution and feed concentration of the hydrogel polymer. The inulin hydrogels exhibited an increase in equilibrium swelling after degradation compared to the swelling before degradation, suggesting that inulinase enzymes are able to diffuse into the inulin hydrogel networks causing bulk degradation.

Headspace fingerprinting as an untargeted approach to compare novel and traditional processing technologies: a case-study on orange juice pasteurisation

As a rule, previous studies have generally addressed the comparison of novel and traditional processing technologies by a targeted approach, in the sense that only the impact on specific quality attributes is investigated. By contrast, this work focused on an untargeted strategy, in order to take into account unexpected and unintended effects of (novel) processing, and to possibly uncover unknown compounds resulting from alternative processing. The potential of headspace GC-MS fingerprinting was explored as a tool to compare the impact of thermal, high pressure (HP) and pulsed electric field (PEF) processing for mild pasteurisation of orange juice. This study demonstrated that when processing conditions are selected based on equivalent microbial safety, the impact of heat, HP and PEF pasteurisation on the volatile profile of orange juice can be considered comparable. During refrigerated storage, however, indirect impact differences were revealed, which were attributed to differences in degree of enzyme inactivation.

Colour and carotenoid changes of pasteurised orange juice during storage.

The correlation of carotenoid changes with colour degradation of pasteurised single strength orange juice was investigated at 20, 28, 35 and 42°C for a total of 32 weeks of storage. Changes in colour were assessed using the CIELAB system and were kinetically described by a zero-order model. L(∗), a(∗), b(∗), ΔE(∗), Cab(∗) and hab were significantly changed during storage (p<0.05). Activation energies for all colour parameters were 64-73 kJ mol(-1). Several carotenoids showed important changes and appeared to have different susceptibilities to storage. A decrease of β-cryptoxanthin was observed at higher temperatures, whereas antheraxanthin started to decrease at lower temperatures. Depending on the time and temperature, changes in carotenoids could be due to isomerisation reactions, which may lead to a perceptible colour change. Although the contribution of carotenoids was recognised to some extent, other reactions seem of major importance for colour degradation of orange juice during storage.

From fingerprinting to kinetics in evaluating food quality changes

Historically, the study of food quality changes during processing, preservation, and storage has evolved from targeted, single-response studies towards studies relying on both targeted and untargeted approaches analyzing multiple responses. In our opinion, future studies should be based on a zoom-in approach in which fingerprinting is used as a multivariate, hypothesis-free starting point to screen for key quality differences in food extracts of differently processed, preserved, and stored foods. By interpreting the identity of selected fingerprint markers in terms of their relevance and consequences for application or connecting the markers to particular food reactions, in a subsequent kinetic study mechanistic as well as quantitative insight into the effect of extrinsic processing variables on quality changes can be obtained.