Small Molecular Weight Substances Research Articles

PS-C09-13: NEW COMPREHENSIVE THERAPEUTIC STRATEGY FOR HYPERTENSION AND UREMIA USING INORGANIC SUBSTANCES WITH SPECIAL ADSORPTION PROPERTIES

Background: In order to remove uremic toxins accumulated in patients with chronic kidney disease (CKD), removal of uremic toxin-causing substances from the intestinal tract by administration of spherical adsorbed charcoal and removal of uremic toxins from the blood by hemodialysis are being performed. However, existing treatment methods are still inadequate for the removal of protein-bound uremic toxins (PBUT) and other medium- to large-sized uremic toxins, which leads to a decreased quality of life and worse prognosis in CKD patients. In order to solve this remaining problem, we are currently investigating the use of inorganic materials for the treatment of uremia. Methods: To evaluate the adsorption performance of our inorganic material, we compared the adsorption performance of various uremic substances in solution, healthy subjects’ plasma, and hemodialysis patients’ plasma, using Kremezin® as a control. Results: Kremezin® was able to adsorb small molecular weight substances in each solution and plasma, while medium to large molecules were poorly adsorbed. On the other hand, the inorganic material we are developing has high adsorption performance not only for small molecules but also for medium to large molecules including inflammatory cytokines and PBUT, and selectively adsorbs cations such as sodium, potassium, and inorganic phosphorus. Conclusion: Inorganic substances with special adsorption performance adsorbed not only uremic substances but also cations, whose accumulation is a problem in CKD patients. Therefore, the inorganic adsorbent may contribute not only to the treatment of uremia but also to the comprehensive treatment of hypertension, hyperkalemia, and CKD-MBD, which are common complications in CKD patients.

Self-Blowing Non-Isocyanate Polyurethane Foams Based on Hydrolysable Tannins

Non-isocyanate polyurethane (NIPU) foams using a hydrolysable tannin, also vulgarly called tannic acid, namely here commercial chestnut wood tannin extract was prepared. Compression strength did not appear to depend on the foam apparent density while the formulation composition of the NIPU foams has been shown to be more determinant. These NIPU foams appeared to be self-extinguishing once the high temperature flame is removed. The ignition time gave encouraging results but for improved fire resistance the foams may need some fire-retardant addition. FTIR spectrometry showed the formation of non-isocyanate urethane linkages. Thermogravimetric analysis indicated a good thermal resistance of these foams, with thermal degradation following four phases. First in the interval 25°C–120°C range, mainly evaporation of water occurs with a maximal loss of 10% weight. In the 150°C–450°C temperature range foams mass loss is of almost 70%. In particular in the 125°C–275°C range occurs the degradation of some small molecular weight substances. In the 500°C–790°C temperature range the foams do not present any further large degradation.

Upcycling glycerin and vinasse by means of microalgae cultivation.

In 2019, the biodiesel / ethanol biofuels sector generated glycerol and vinasse by-products in significant quantities (476 million and 466 billion liters, respectively). Therefore, it is necessary to reuse or treat these products to reduce their environmental impacts. Using them to support the cultivation of microalgae is a sustainable way of valuing and treating these residues. The objective of this work is to systematize the scientific articles that report their use for the cultivation of microalgae and, consequently, the type of algal bioproducts commonly obtained. Glycerol can be used as a source of carbon in algal mixotrophic growth and, therefore, it can increase algal biomass production. The same process can happen with several small molecular weight substances present in the vinasse, but the concentration of nitrogen and phosphorus is what makes such effluent attractive for the algal cultivation process. Although there are scientific studies describing the use of these substances for algal growth, this work highlights that they vary significantly according to the reports regarding the operation of such culturing system.

Effect of hyperthermia and acidosis on equine skeletal muscle mitochondrial oxygen consumption

The skeletal muscle of exercising horses develops pronounced hyperthermia and acidosis during strenuous or prolonged exercise, with very high tissue temperature and low pH associated with muscle fatigue or damage. The purpose of this study was to evaluate the individual effects of physiologically relevant hyperthermia and acidosis on equine skeletal muscle mitochondrial function, using ex vivo measurement of oxygen consumption to assess the function of different mitochondrial elements. Fresh triceps muscle biopsies from 6 healthy unfit Thoroughbred geldings were permeabilised to permit diffusion of small molecular weight substrates through the sarcolemma and analysed in a high resolution respirometer at 38, 40, 42, and 44 °C, and pH=7.1, 6.5, and 6.1. Oxygen consumption was measured under conditions of non-phosphorylating (leak) respiration and phosphorylating respiration through Complex I and Complex II. Data were analysed using a one-way repeated measures ANOVA and data are expressed as mean ± standard deviation. Leak respiration was ~3-fold higher at 44 °C compared to 38 °C regardless of electron source (Complex I: 22.88±3.05 vs 8.08±1.92 pmol O2/mg/s), P=0.002; Complex II: 79.14±23.72 vs 21.43±11.08 pmol O2/mg/s, P=0.022), resulting in a decrease in efficiency of oxidative phosphorylation. Acidosis had minimal effect on mitochondrial respiration at pH=6.5, but pH=6.1 resulted in a 50% decrease in mitochondrial oxygen consumption. These results suggest that skeletal muscle hyperthermia decreases the efficiency of oxidative phosphorylation through increased leak respiration, thus providing a specific biochemical basis for hyperthermia-induced muscle fatigue. The effect of myocellular acidosis on mitochondrial respiration was minimal under typical levels of acidosis, but atypically severe acidosis can lead to impairment of mitochondrial function.

A real-time in vitro assay to evaluate the release of macromolecules from liposomes.

The availability of a real-time assay to experimentally investigate the release of encapsulated proteins would be beneficial given the interest in the use of liposomes as a drug delivery vehicle. Although simple assays for small molecular weight substances exist, assays to evaluate macromolecules do not. Here we describe a method that detects the release of model macromolecules from liposomes in real time. The assay employs the intermolecular distance-dependent phenomenon of fluorescence resonance energy transfer (FRET) between the fluorophore donor, fluorescein (FITC), and fluorescent quencher, QSY® 9. The macromolecular species were conjugated to the markers fluorescein (44kDa dextran) and QSY® 9 (67kDa bovine serum albumin, BSA). Following confirmation of quenching between FITC-Dex and QSY® 9-BSA, liposomes were loaded with the macromolecular markers and subjected to various treatments (high-pressure extrusion and Triton X solubilisation) to cause release from liposomes. An increase in FITC fluorescence was observed when liposomes were subjected to extrusion cycles. Surprisingly, the addition of Triton X did not cause an increase in fluorescence probably because the FRET pair became associated with mixed micelles. This assay method should be useful in studies to investigate the mechanisms by which macromolecules are released from liposomes, particularly when liposomes are exposed to release-triggers (eg, temperature change, pH change, ultrasound). Such understanding will underpin the formulation of triggered liposomal delivery systems for macromolecules.

SPR Biosensing MUA/Poly-L-lysine Platform for the Detection of 2,4-Dinitrophenol as Small Molecule Model System

Surface Plasmon Resonance assays are being developed as alternative biodetection methods for a great number of pesticides and toxins. These substances typically have low molecular weight, making it necessary to perform competitive inhibition immunoassays. In most of the cases, the strategy is to immobilize a protein derivative of the analyte, which usually involves the appearance of nonspecific protein binding which limits the detection range of the assay. In this work we present results of a poly-L-lysine (Au-MUA-PLL) based sensor platform for quantitative determination of 2,4-dinitrophenol as model system for small molecular weight substances detection. The prepared sensor chip was characterized by means of Atomic Force Microscopy, Surface Plasmon Resonance, and Surface Enhanced Raman Spectroscopy. Experiments verified the absence of nonspecific protein adsorption to Au-MUA-PLL surfaces and the improvement of the competitive inhibition assays performance in comparison with single and mixed thiol self-assembled monolayers. The possibility of directly immobilizing 2,4-dinitrophenol to the poly-L-lysine containing platforms leads to an improvement in the detection of the soluble analyte by the competitive inhibition assay avoiding undesirable nonspecific protein adsorption. Therefore, Au-MUA-PLL surfaces constitute a suitable alternative for quantitative detection of small molecules when nonspecific adsorption cannot be avoided.

Biomimetic collagen I and IV double layer Langmuir–Schaefer films as microenvironment for human pluripotent stem cell derived retinal pigment epithelial cells

The environmental cues received by the cells from synthetic substrates in vitro are very different from those they receive in vivo. In this study, we applied the Langmuir–Schaefer (LS) deposition, a variant of Langmuir–Blodgett technique, to fabricate a biomimetic microenvironment mimicking the structure and organization of native Bruch's membrane for the production of the functional human embryonic stem cell derived retinal pigment epithelial (hESC-RPE) cells. Surface pressure-area isotherms were measured simultaneously with Brewster angle microscopy to investigate the self-assembly of human collagens type I and IV on air-subphase interface. Furthermore, the structure of the prepared collagen LS films was characterized with scanning electron microscopy, atomic force microscopy, surface plasmon resonance measurements and immunofluorescent staining. The integrity of hESC-RPE on double layer LS films was investigated by measuring transepithelial resistance and permeability of small molecular weight substance. Maturation and functionality of hESC-RPE cells on double layer collagen LS films was further assessed by RPE-specific gene and protein expression, growth factor secretion, and phagocytic activity. Here, we demonstrated that the prepared collagen LS films have layered structure with oriented fibers corresponding to architecture of the uppermost layers of Bruch's membrane and result in increased barrier properties and functionality of hESC-RPE cells as compared to the commonly used dip-coated controls.

Self-built microdialysis probes with improved recoveries of ATP and neuropeptides.

Microdialysis is an established technique for collecting small molecular weight substances (e.g. neurotransmitter and energy metabolites) from the extracellular space. The major element of microdialysis is the probe which contains a semi-permeable membrane and is exposed to the interstitial space. As the microdialysis technique has major advantages, e.g. versatility and use in awake animals, commercially produced probes are in great demand. We here present the design of a probe assembly step by step which will enable researchers to build custom-made probes. Probe recoveries of substances with different molecular weight (ranging from 100 to 1600 Da) were compared for three different probes (CMA 12 Elite probe, custom-made 10 kDa and 30 kDa probes). Recoveries of glucose, lactate, acetylcholine, choline, ATP and the neuropeptides angiotensin II, substance P and somatostatin are presented. We found that the 10 kDa probe is only useful for compounds up to 1000 Da while recoveries of the CMA-12 Elite Probe are variable and apparently dependent on ionic charges of analytes. The recovery of the custom-made 30 kDa probe is highest and evidently not influenced by physicochemical parameters of analytes. In a further optimization step, we describe the use of ZipTip(®) μC-18 collection tips to replace the outlet tubing when purifying the dialysate for MALDI-MS measurements of neuropeptides. The results show that self-built microdialysis probes can be equally or more effective than commercially available probes. Self-built microdialysis probes with large pore-membranes are capable of dialyzing ATP and neuropeptides.

Blood brain barrier is impermeable to solutes and permeable to water after experimental pediatric cardiac arrest

Pediatric asphyxial cardiac arrest (CA) results in unfavorable neurological outcome in most survivors. Development of neuroprotective therapies is contingent upon understanding the permeability of intravenously delivered medications through the blood brain barrier (BBB). In a model of pediatric CA we sought to characterize BBB permeability to small and large molecular weight substances. Additionally, we measured the percent brain water after CA. Asphyxia of 9min was induced in 16–18 day-old rats. The rats were resuscitated and the BBB permeability to small (sodium fluorescein and gadoteridol) and large (immunoglobulin G, IgG) molecules was assessed at 1, 4, and 24h after asphyxial CA or sham surgery. Percent brain water was measured post-CA and in shams using wet-to-dry brain weight. Fluorescence, gadoteridol uptake, or IgG staining at 1, 4h and over the entire 24h post-CA did not differ from shams, suggesting absence of BBB permeability to these solutes. Cerebral water content was increased at 3h post-CA vs. sham. In conclusion, after 9min of asphyxial CA there is no BBB permeability over 24h to conventional small or large molecule tracers despite the fact that cerebral water content is increased early post-CA indicating the development of brain edema. Evaluation of novel therapies targeting neuronal death after pediatric CA should include their capacity to cross the BBB.

Bagasse Wet-Stored with the Hypochlorite Bleaching Waste Water

In this paper, the bagasse was wet stored by hypochlorite bleaching waste water with or without chlorine. The dissolution ability of lignin, total sugar and reducing sugar was investigated. Then the effluent properties with the wet storage time prolonging were tested. The results showed that some small molecular weight substances were dissolved from baggase, such as sugar and lignin. And the dissolution ability of hypochlorite bleaching waste water with chlorine was better than that of hypochlorite bleaching waste water without chlorine. And the change trend of effluent properties for the two wet storage system were similar. With the wet storage time extending, the dissolved substances were degraded, COD and chroma of effluent were decreased, and the properties of effluent were improved.

Structural Diversity of Neuritogenic Substances and their Application Perspective

Small molecular weight substances are functional, as neurotrophic factors can be developed as therapeutic drugs to treat neurodegenerative disorder. Recently, a large number of natural and synthetic neuritogenic compounds have been discovered. These compounds have various structural features, including terpenoids, lipids, alkaloids, steroid glycosides, small molecular peptides, and so on. Some of them possess not only neurotrophic properties but also neuroprotective activities. The structure-activity relationships (SARs) and mechanism of action of some important compounds have been studied intensively. Increasing experimental evidence suggests that several of these compounds can be promising candidates for drug development.

Potential Non-Hypoxic/Ischemic Causes of Increased Cerebral Interstitial Fluid Lactate/Pyruvate Ratio: A Review of Available Literature

Microdialysis, an in vivo technique that permits collection and analysis of small molecular weight substances from the interstitial space, was developed more than 30 years ago and introduced into the clinical neurosciences in the 1990s. Today cerebral microdialysis is an established, commercially available clinical tool that is focused primarily on markers of cerebral energy metabolism (glucose, lactate, and pyruvate) and cell damage (glycerol), and neurotransmitters (glutamate). Although the brain comprises only 2% of body weight, it consumes 20% of total body energy. Consequently, the ability to monitor cerebral metabolism can provide significant insights during clinical care. Measurements of lactate, pyruvate, and glucose give information about the comparative contributions of aerobic and anaerobic metabolisms to brain energy. The lactate/pyruvate ratio reflects cytoplasmic redox state and thus provides information about tissue oxygenation. An elevated lactate pyruvate ratio (>40) frequently is interpreted as a sign of cerebral hypoxia or ischemia. However, several other factors may contribute to an elevated LPR. This article reviews potential non-hypoxic/ischemic causes of an increased LPR.

Quantitative NMR spectroscopy of biologically active substances and excipients

Biologically active ingredients and excipients are the essentials of a drug formulation, such as a tablet, dragee, solution, etc. Quality control of such substances thus plays a pivotal role in the production process of pharmaceutical drugs. Since these agents often exhibit complex structures, consist of multiple components, or lack of a chromophore, traditional means of characterization are often not feasible. Furthermore, substances of small molecular weight or strong polar character generally exhibit poor chromatographic properties, thus, conventional procedures such as high-performance liquid chromatography are often not applicable. Instead, quantitative nuclear magnetic resonance (qNMR) spectroscopy has emerged as an alternative or orthogonal method in drug analysis. In this review, we elaborate on the application of qNMR to three important classes of biological substances, namely polysaccharides, amino acids, and lipids, and demonstrate the benefits of this modern tool in contrast to traditional techniques.

High-quality dialysis: a lesson from the Japanese experience: Effects of membrane material on nutritional status and dialysis-related symptoms.

High-quality dialysis does not always mean high efficiency; dialysis should maintain nutritional balance and full biocompatibility. In undergoing treatment with polymethylmethacrylate (PMMA) and/or ethylene vinyl alcohol copolymer (EVAL) membrane dialysers, the body weight decrease caused by polysulfone membrane has been dramatically improved for those receiving predilution online haemodiafiltration (HDF) as well. These membranes are assumed to somewhat suppress the clearance of small molecular weight substances to maintain an exquisite balance of broadly removing low molecular weight proteins. This removal process is assumed to be extremely close to the balance maintained by the clearing characteristics of the kidneys. On the other hand, fluid purification is also one of the important factors in high-quality dialysis. Bacteriological contamination of dialysis fluid is one of the serious factors that deteriorate the biocompatibility of dialysis therapy.From this therapeutic concept, the patient survival rate is excellent in our facilities: the 1-year survival rate is 91.1% and the 5-year survival rate is 76.6%, although the mean age of our patients is 69 years. We usually adjust the therapeutic modality based on patient complaints, and we call this concept ‘patient-oriented dialysis’ (POD). In the POD system, the prevalence of uraemic pruritus or sleep disturbances was lower than that of the DOPPS. The protein-leaking dialysis modalities with PMMA, EVAL or predilution online HDF form the key concept in the POD system.

Structures of Human Cytochrome P-450 2E1: INSIGHTS INTO THE BINDING OF INHIBITORS AND BOTH SMALL MOLECULAR WEIGHT AND FATTY ACID SUBSTRATES

Human microsomal cytochrome P-450 2E1 (CYP2E1) monooxygenates > 70 low molecular weight xenobiotic compounds, as well as much larger endogenous fatty acid signaling molecules such as arachidonic acid. In the process, CYP2E1 can generate toxic or carcinogenic compounds, as occurs with acetaminophen overdose, nitrosamines in cigarette smoke, and reactive oxygen species from uncoupled catalysis. Thus, the diverse roles that CYP2E1 has in normal physiology, toxicity, and drug metabolism are related to its ability to metabolize diverse classes of ligands, but the structural basis for this was previously unknown. Structures of human CYP2E1 have been solved to 2.2 angstroms for an indazole complex and 2.6 angstroms for a 4-methylpyrazole complex. Both inhibitors bind to the heme iron and hydrogen bond to Thr303 within the active site. Complementing its small molecular weight substrates, the hydrophobic CYP2E1 active site is the smallest yet observed for a human cytochrome P-450. The CYP2E1 active site also has two adjacent voids: one enclosed above the I helix and the other forming a channel to the protein surface. Minor repositioning of the Phe478 aromatic ring that separates the active site and access channel would allow the carboxylate of fatty acid substrates to interact with conserved 216QXXNN220 residues in the access channel while positioning the hydrocarbon terminus in the active site, consistent with experimentally observed omega-1 hydroxylation of saturated fatty acids. Thus, these structures provide insights into the ability of CYP2E1 to effectively bind and metabolize both small molecule substrates and fatty acids.

Inhibition of gap junction currents by the abused solvent toluene

Abused inhalants are a large class of compounds that are inhaled for their intoxicating and mood altering effects. They include chemicals with known therapeutic uses such as anesthetic gases as well as volatile organic solvents like toluene that are found in paint thinners and adhesives. Because of their widespread commercial use and availability, inhalants are often among the first drugs that children encounter and use of these compounds is often associated with adverse acute and long-term consequences. The cellular and molecular sites of action for abused inhalants is not well known although recent studies report that toluene and other organic solvents alter the activity of specific ligand- and voltage-gated ion channels that regulate cellular excitability. As part of an ongoing effort to define molecular sites of action for abused inhalants, this study examined the effect of toluene on the function of gap junction proteins endogenously expressed in human embryonic kidney (HEK 293) cells. Gap junctions allow cell-to-cell electrical communication as well as passage of small molecular weight substances and are critical for synchronizing cellular activity in certain tissues. Gap junction currents in HEK 293 cells were measured during brief voltage steps using patch-clamp electrophysiology and were blocked by known gap junction blockers confirming expression of connexin proteins in these cells. Toluene dose-dependently inhibited these conductances with threshold effects appearing at approximately 0.4 mM and near complete inhibition occurring at concentrations of 1 mM and higher. The estimated EC 50 value for toluene inhibition of gap junction currents in HEK 293 cells was 0.57 mM. The results of these studies suggest that volatile solvents including toluene may produce some of their effects by disrupting inter-cellular communication mediated by gap junction proteins.

POOR NUTRITIONAL STATUS AND INFLAMMATION: The Dose of Dialysis in Hemodialysis Patients: Impact on Nutrition

ABSTRACTMultiple lines of evidence have indicated that the dose of hemodialysis impacts upon patient outcome. Among these outcome measures, nutrition is inextricably linked to the adequacy of the treatment. All of the methods of determining dialysis adequacy are based on assessing the removal of toxic substances retained in renal failure, the majority of which are derivatives of protein metabolism. Urea kinetics, employing urea as a surrogate for quantifying the elimination of small molecular weight nitrogenous substances, is the method that has been most thoroughly validated to date as defining a dose range for thrice‐weekly hemodialysis: Both inadequate and optimal levels of hemodialysis dose have been identified by prospective, randomized clinic trials utilizing Kt/Vurea as the index of adequacy. The impact of urea kinetics on nutritional status during thrice‐weekly hemodialysis is discussed. Recently, in an attempt to improve outcome beyond that achievable with thrice‐weekly hemodialysis, alternative regimens, consisting of daily treatments, have received increasing interest. In order to compare the dose of hemodialysis associated with these regimens with conventional thrice‐weekly regimens in terms of removal of small molecular weight substances, standard Kt/Vurea, a parameter that combines treatment dose with treatment frequency, and thus allows for various intermittent therapies to be compared to continuous therapy, must be used. In addition, membrane flux and middle molecule removal, factors that have not yet been well defined as parameters of adequacy during thrice‐weekly regimens, may be shown to be important indices with longer hemodialysis treatments, particularly daily nocturnal hemodialysis. The impact that these alternative regimens have had on nutritional status in hemodialysis patients and how they compare to conventional therapy are important considerations.

Impact of the type of dialyser on the clinical outcome in chronic haemodialysis patients: does it really matter?

Despite the relative efficiency of modern equipment, haemodialysis (HD) remains inferior to normal kidney function for several reasons. First of all, HD treatment results in a weekly clearance of small molecular weight substances of only 10–15ml/min, as compared with 90–120ml/min for normal kidneys. Secondly, so-called ‘middle molecules’ (MMs) as well as some larger peptides, which are normally excreted or metabolized by the healthy kidney, are cleared inadequately and will therefore accumulate in chronic HD (CHD) patients. Thirdly, various undesirable interactions, including both shortand long-term side effects—termed bio(in)compatibility—may occur between the living organism and the extracorporeal circuit (ECC) [1]. In the last decades, a variety of new dialysers, differing in design, material, membrane surface area and permeability, have been developed. Very recently, one of the world’s largest companies involved in the production and development of dialysers replaced its total set of low-flux (LF) dialysers by a new one with better urea clearances and higher ultrafiltration (UF) coefficients. Actually, these new devices do not fulfil the criteria for LF (UF <10ml/mmHg/h), but must be considered medium flux (UF 10–20ml/mmHg/h). However, today there is no general agreement as to whether the use of dialysers with an increased urea removal and/or a higher UF rate is associated with a better clinical course. In fact, cardiovascular disease (CVD) is already observed in the pre-dialysis phase and is the major cause of death in end-stage renal disease (ESRD) [2]. Dialysis patients suffer from atherosclerotic complications at a relatively young age and die relatively young from ischaemic heart disease [3]. Therefore, it is conceivable that individual patient factors, such as the burden of CVD, greatly surpass the influence of the dialysis equipment in this respect. In this review, we will first discuss various aspects of the dialyser which have been associated with the clinical outcome in CHD patients. Besides the type of membrane, various aspects of bio(in)compatibility and solute mass transport are discussed. Thereafter, we will summarize the influence of the type of dialyser on a number of indirect parameters for CVD, including several biochemical and functional tests. Finally, we will review critically the relevant literature to determine whether the choice of the dialyser contributes to the life expectancy of patients with ESRD.

血しょう交換を用いず持続的血液ろ過および新鮮凍結血しょう輸注で治療した劇症肝不全の３例

Plasma exchange (PE) is considered to be essential for the treatment of fulminant hepatic failure. However, small or middle-sized abnormal molecular weight substances are suspected to be a cause of hepatic encephalopathy. We report three patients with fulminant hepatic failure who were treated without PE and discuss the role of PE in the treatment of fulminant hepatic failure. We performed continuous hemofiltration (CHF) in these three patients, using large quantities of filtration and fresh frozen plasma (FFP) transfusion. PE was not performed in any of these cases. All patients were conscious after the completion of their treatments. CHF is useful for treating encephalopathy caused by fulminant hepatic failure and may be an effective means of replacing the liver's normal antidotal functions. The method can be used to remove small and middlesize molecular weight substances that are suspected of being hepatic toxins. FFP transfusion is a viable alternative to the normal liver's synthetic functions. The outcome of the three patients presented here suggests that PE may not be needed for the treatment of fulminant hepatic failure. Instead, CHF and FFP transfusion may be critical for the treatment of fulminant hepatic failure.

Study of release kinetics of small and high molecular weight substances dispersed into spray-dried ethylcellulose microspheres

Spray-dried ethylcellulose microspheres were used as matrices for the encapsulation of a fungal lactase and/or small paramagnetic probes (Tempol or Tempo). Their dissolution in water was studied. Kinetics fitted with the model Q= kt n of Korsemeyer et al. [Int. J. Pharm. 15 (1983) 25] exhibited a non-Fickian diffusion. The calculated diffusional exponent ( n) values were near 0.26 whatever the encapsulated probes. The release rates ( k) were only slightly different for paramagnetic probes and lactase. This result indicated that the probes’ release mechanisms are not diffusion controlled. Other factors such as matrix porosity and probe solubility in the matrix and in water could influence the probes’ release rate.