Synthetic and natural mucoadhesive biomaterials in optimized galenical formulations are potentially useful for the transmucosal delivery of active ingredients to improve their localized and prolonged effects. Chitosans (CS) have potent mucoadhesive characteristics, but the exact mechanisms underpinning such interactions at the molecular level and the role of the specific structural properties of CS remain elusive. In the present study we used a combination of microviscosimetry, zeta potential analysis, isothermal titration calorimetry (ITC) and fluorescence quenching to confirm that the soluble fraction of porcine stomach mucin interacts with CS in water or 0.1 M NaCl (at c < c*; relative viscosity, η(rel), ∼ 2.0 at pH 4.5 and 37 °C) via a heterotypic stoichiometric process significantly influenced by the degree of CS acetylation (DA). We propose that CS-mucin interactions are driven predominantly by electrostatic binding, supported by other forces (e.g., hydrogen bonds and hydrophobic association) and that the DA influences the overall conformation of CS and thus the nature of the resulting complexes. Although the conditions used in this model system are simpler than the typical in vivo environment, the resulting knowledge will enable the rational design of CS-based nanostructured materials for specific transmucosal drug delivery (e.g., for Helicobacter pylori stomach therapy).

Temperature profiles within the human body are highly dependent on the geometry and inhomogeneity of the body. Physical parameters such as density and heat conductivity of the various tissues and variables such as blood flow and metabolic heat production of different organs are spatially distributed and thereby influence the temperature profiles within the human body. Actual physiological knowledge allows one to take into account up to 54 different spatially distributed values for each parameter. An adequate representation of the anatomy of the body requires a spatial three-dimensional grid of at least 0.5-1.0 cm. This is achieved by photogrammetric treatment of three-dimensional anatomic models of the human body. As a first essential result, the simulation system has produced a realistic picture of the topography of temperatures under neutral conditions. Compatibility of reality and simulation was achieved solely on the basis of physical considerations and physiological data base. Therefore the simulation is suited to the extrapolation of temperature profiles that cannot be obtained experimentally.

Mucoadhesive materials adhere persistently to mucosal surfaces. A mucoadhesive delivery system could therefore facilitate the controlled release of drugs and optimize their bioavailability in mucosal tissues. Polysaccharides are the most versatile class of natural polymers for transmucosal drug delivery. We used microviscosimetry to explore the mucoadhesion of a library of polysaccharide families with diverse structural characteristics as a first step towards the rational design of mucoadhesive polysaccharide-based nanoformulations. Here we show that the magnitude of deviation between the viscosity of mixed polysaccharide-mucin solutions and the corresponding individual stock solutions can indicate underlying molecular interactions. We found that nonlinear monotonic curves predicted a correlation between the magnitude of interaction and the ability of polysaccharide coils to contract in the presence of salt (i.e. chain flexibility). Charge-neutral polysaccharides such as dextran and Streptococcus thermophilus exopolysaccharide did not interact with mucin. Synchrotron small-angle X-ray scattering (SAXS) data supported the previously described structural features of mucin. Furthermore, high-q scattering data (i.e. sensitive to smaller scales) revealed that when mucin is in dilute solution (presumably in an extended conformation) in the presence of low-Mw alginate, its structure resembles that observed at higher concentrations in the absence of alginate. This effect was less pronounced in the case of high-Mw alginate but the latter influenced the bulk properties of mucin-alginate mixtures (e.g. hydrodynamic radius and relative viscosity) more prominently than its low-Mw counterpart.

The aim of human temperature regulation is to protect body processes by establishing a relative constancy of deep body temperature (regulated variable), in spite of external and internal influences on it. This is basically achieved by a distributed multi-sensor, multi-processor, multi-effector proportional feedback control system. The paper explains why proportional control implies inherent deviations of the regulated variable from the value in the thermoneutral zone. The concept of feedback of the thermal state of the body, conveniently represented by a high-weighted core temperature (T (c)) and low-weighted peripheral temperatures (T (s)) is equivalent to the control concept of "auxiliary feedback control", using a main (regulated) variable (T (c)), supported by an auxiliary variable (T (s)). This concept implies neither regulation of T (s) nor feedforward control. Steady-states result in the closed control-loop, when the open-loop properties of the (heat transfer) process are compatible with those of the thermoregulatory processors. They are called operating points or balance points and are achieved due to the inherent property of dynamical stability of the thermoregulatory feedback loop. No set-point and no comparison of signals (e.g. actual-set value) are necessary. Metabolic heat production and sweat production, though receiving the same information about the thermal state of the body, are independent effectors with different thresholds and gains. Coordination between one of these effectors and the vasomotor effector is achieved by the fact that changes in the (heat transfer) process evoked by vasomotor control are taken into account by the metabolic/sweat processor.

In this paper a dynamic model of the human/ clothing/environment-system is developed. The human body (controlled system) is subdivided into six segments consisting of the head, trunk, arms, hands, legs and feet. Each segment is further divided into the core, muscle, fat, and skin layer. The afferent signal of the controlling system is composed of the weighted temperatures measured by thermal receptors at sites distributed in the body. The difference between this signal and its threshold activates the thermoregulatory actions: vasomotor changes, metabolic heat production and sweat production. The model considers the competition between skin and muscle blood flow during exercise in hot environments because of limited cardiac capacity, as well as cold induced vasodilatation. Additionally a combined model of heat and mass transfer from the skin through clothing to the environment is developed and incorporated into the thermoregulatory model. The human/clothing model can be used to investigate the interaction between the human body, clothing and environment. The model is validated by comparing the simulation with experimental results under different conditions: heat, cold, exercise, clothing and transient phases. It turns out that the simulation is compatible with the experimental results. We conclude that the model can be applied in a broad range of environmental conditions. Application of the model is easy via a user-friendly interface i.e. a WINDOWS-shell.